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Biomedical subjects

F Navarro

Publications and source records attributed to F Navarro.

At least 109 records · Page 6Linked to original sources
PubMed1997

The CD94/NKG2 C-type lectin receptor complex: involvement in NK cell-mediated recognition of HLA class I molecules.

A multigene family to human Ig-SF receptors and members of the murine Ly49 C-type lectin family are involved in natural killer (NK) cell-mediated recognition of MHC class I molecules. The human CD94 glycoprotein covalently assembles with different C-type lectins of the NKG2 family. By functional criteria, the CD94/NKG2-A (kp43) receptor complex appears also involved in NK cell-mediated recognition of different HLA class I allotypes. Similarly to the other NK inhibitory receptors, NKG2-A contains cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMS). By contrast, NK clones bearing different receptor complex (CD94/p39) are triggered upon ligation by CD94-specific monoclonal antibodies (MAbs); the p39 subunit is likely encoded by other member(s) of the NKG2 family. Expression of different CD94/NKG2 complexes is warranted to precisely assess their specific interaction with HLA class I molecules, and the molecular basis for their divergent functional properties.

Animals↗
PubMed1997

Role of cytochrome b5 reductase on the antioxidant function of coenzyme Q in the plasma membrane.

Cytochrome b5 reductase purified from liver plasma membrane reduces coenzyme Q (CoQ) in reconstituted liposomes in the absence of cytochrome b5. Both CoQ and its reductase are responsible for the reduction of the ascorbate free radical at the cell surface. Thus, NADH-CoQ reductase represents a partial reaction of NADH-AFR reductase in the plasma membrane. Cytochrome b5 reductase maintains CoQ and ascorbate in their reduced state to support antioxidations. Reduced CoQ prevents lipid peroxidation in liposomes and plasma membranes. Also, oxidized CoQ can prevent lipid peroxidations in the presence of cytochrome b5 reductase and NADH. Addition of CoQ to intact cells prevents serum withdrawal-induced lipid peroxidation and apoptosis. The prevention of apoptosis by CoQ is independent of the bcl-2 protein content in the cell. Antioxidants that act at the plasma membrane as CoQ and ascorbate would represent a first barrier to protect lipids from oxidative stress and subsequent apoptosis. Cytochrome b5 reductase is then an enzyme leading this function at the plasma membrane. These data support the idea that when the plasma membrane barrier fails, bcl-2 protein would be required to prevent cell death.

Animals↗
PubMed1997

[Factors related to the appearance of peripheral vascular complications after taneous cardiovascular interventions].

BACKGROUND: Percutaneous diagnostic and therapeutic cardiac catheterization procedures carries some risks, most of them related to the appearance of peripheral vascular complications. These complications imply additional treatments for the patient including vascular surgery, longer hospital stays and increased costs. Some clinical and procedural variables have been pointed out as independent predictors of appearance of vascular complications. Nevertheless, no information have been reported concerning to the influence of the experience of the cardiologist who performs the procedure or provides the local hemostasia and the rate of vascular complications. OBJECTIVE: To characterise the type and incidence of peripheral vascular complications in patients undergoing a percutaneous cardiac procedure, to identify the predictors and to determine the influence of the professional experience and the complexity of the technique in the complications rate. METHODS AND RESULTS: Within 1-year (1994 to 1995) period, 1,008 consecutive patients undergoing a percutaneous cardiovascular procedure (750 diagnostic and 258 therapeutic) were prospectively included. Seventy percent were male. Mean age was 63 +/- 2 years. A total of 55 vascular complications were demonstrated (5.6%): 36 (3.6%) hematomas, 14 (1.4%) pseudoaneurysms, 2 (0.2%) arteriovenous fistula, 2 (0.2%) episodes of limb ischemia and 1 (0.1%) retroperitoneal hematoma. Only 28 (2.8%) were severe complications. By multivariate analysis, only experience to perform hemostasis (OR: 3.36; 95% CI: 1.37-8.22), previous treatment with aspirin (OR: 2.69; 95% IC: 1.31-5.52), left femoral artery puncture (OR: 2.53; 95% IC: 1-1.02), sheath removal later than 60 minutes (OR: 1.02; 95% IC: 1.01-1.04) and hemostasis which lasted > 30 minutes (OR: 1.01; 95% IC: 1-1.02), were independent predictors of vascular complications. CONCLUSIONS: Vascular complications rate after percutaneous cardiovascular procedures was low. Most of them associated to procedural variables and potentially avoidable, with promotion of a well planned policy of training in order to modify the factors involved.

Aged↗
PubMed1997

Antioxidant ascorbate is stabilized by NADH-coenzyme Q10 reductase in the plasma membrane.

Plasma membranes isolated from K562 cells contain an NADH-ascorbate free radical reductase activity and intact cells show the capacity to reduce the rate of chemical oxidation of ascorbate leading to its stabilization at the extracellular space. Both activities are stimulated by CoQ10 and inhibited by capsaicin and dicumarol. A 34-kDa protein (p34) isolated from pig liver plasma membrane, displaying NADH-CoQ10 reductase activity and its internal sequence being identical to cytochrome b5 reductase, increases the NADH-ascorbate free radical reductase activity of K562 cells plasma membranes. Also, the incorporation of this protein into K562 cells by p34-reconstituted liposomes also increased the stabilization of ascorbate by these cells. TPA-induced differentiation of K562 cells increases ascorbate stabilization by whole cells and both NADH-ascorbate free radical reductase and CoQ10 content in isolated plasma membranes. We show here the role of CoQ10 and its NADH-dependent reductase in both plasma membrane NADH-ascorbate free radical reductase and ascorbate stabilization by K562 cells. These data support the idea that besides intracellular cytochrome b5-dependent ascorbate regeneration, the extracellular stabilization of ascorbate is mediated by CoQ10 and its NADH-dependent reductase.

Animals↗
PubMed1997

Epidemiology of an unusually prolonged outbreak of typhoid fever in Terrassa, Spain.

An unusually prolonged outbreak of typhoid fever, from 1988 to 1994, in Terrassa (Barcelona, Spain), was caused by a casual food handler who was a carrier. The pattern of this outbreak suggested intermittent low-level exposure to Salmonella typhi. We found 70 patients with S. typhi infections, 52 of whom were available for study. Medical records were reviewed and patients were interviewed with use of a standard questionnaire. Phage typing and pulsed-field gel electrophoresis (PFGE) for strain subtyping were used to confirm the epidemiological data. The 27 outbreak strains shared the same phage type and the same PFGE pattern. Four sporadic strains shared the same phage type as the outbreak strain. PFGE was found to be useful for differentiating strains for epidemiological purposes.

Adult↗
PubMed1997

Argon pneumoperitoneum is more dangerous than CO2 pneumoperitoneum during venous gas embolism.

UNLABELLED: We investigated the possibility of using argon, an inert gas, as a replacement for carbon dioxide (CO2). The tolerance of argon pneumoperitoneum was compared with that of CO2 pneumoperitoneum. Twenty pigs were anesthetized with enflurane 1.5%. Argon (n = 11) or CO2 (n = 9) pneumoperitoneum was created at 15 mm Hg over 20 min, and serial intravenous injections of each gas (ranging from 0.1 to 20 mL/kg) were made. Cardiorespiratory variables were measured. Transesophageal Doppler and capnographic monitoring were assessed in the detection of embolism. During argon pneumoperitoneum, there was no significant change from baseline in arterial pressure and pulmonary excretion of CO2, mean systemic arterial pressure (MAP), mean pulmonary artery pressure (PAP), or systemic and pulmonary vascular resistances, whereas CO2 pneumoperitoneum significantly increased these values (P < 0.05). During the embolic trial and from gas volumes of 2 and 0.2 mL/kg, the decrease in MAP and the increase in PAP were significantly higher with argon than with CO2 (P < 0.05). In contrast to CO2, argon pneumoperitoneum was not associated with significant changes in cardiorespiratory functions. However, argon embolism seems to be more deleterious than CO2 embolism. The possibility of using argon pneumoperitoneum during laparoscopy remains uncertain. IMPLICATIONS: Laparoscopic surgery requires insufflation of gas into the peritoneal cavity. We compared the hemodynamic effects of argon, an inert gas, and carbon dioxide in a pig model of laparoscopic surgery. We conclude that argon carries a high risk factor in the case of an accidental gas embolism.

Animals↗
PubMed1997

Repeat hepatectomy for colorectal liver metastases.

OBJECTIVE: The authors assess the long-term results of repeat hepatectomies for recurrent metastases of colorectal cancer and determine the factors that can predict survival. SUMMARY BACKGROUND DATA: Safer techniques of hepatic resection have allowed surgeons to consider repeat hepatectomy for colorectal metastases in an increasing number of patients. However, higher operative bleeding and increased morbidity have been reported after repeat hepatectomies, and the long-term benefit of these procedures needs to be evaluated. STUDY POPULATION: Sixty-four patients from a group of 243 patients resected for colorectal liver metastases were submitted to 83 repeat hepatectomies (64 second, 15 third, and 4 fourth hepatectomies). Combined extrahepatic surgery was performed in 21 (25%) of these 83 repeat hepatectomies. RESULTS: There was no intraoperative or postoperative mortality. Operative bleeding was not significantly increased in repeat hepatectomies as compared to first resections. Morbidity and duration of hospital stay were comparable to first hepatectomies. Overall and disease-free survival after a second hepatectomy were 60% and 42%, respectively, at 3 years and 41% and 26%, respectively, at 5 years. Factors of prognostic value on univariate analysis included the curative nature of first and second hepatectomies (p = 0.04 and p = 0.002, respectively), an interval between the two procedures of more than 1 year (p = 0.003), the number of recurrent tumors (p = 0.002), serum carcinoembryonic antigen levels (p = 0.03), and the presence of extrahepatic disease (p = 0.03). Only the curative nature of the second hepatectomy and an interval of more than 1 year between the two procedures were independently related to survival on multivariate analysis. CONCLUSIONS: Repeat hepatectomies can provide long-term survival rates similar to those of first hepatectomies, with no mortality and comparable morbidity. Combined extrahepatic surgery can be required to achieve tumor eradication. Repeat hepatectomies appear worthwhile when potentially curative.

Adult↗
PubMed1997

Structure and function of the CD94 C-type lectin receptor complex involved in recognition of HLA class I molecules.

A multigene family of immunoglobulin superfamily (Ig-SF) killer cell inhibitory receptors (KIRs) specifically recognize HLA class I molecules, while the interaction with H-2 products is mediated by members of the murine Ly49 C-type lectin family. A common structural feature of these receptors with inhibitory function is the presence of cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that couple them to SHP phosphatases. Strong support for the involvement of the CD94 C-type lectin receptor complex in NK cell-mediated recognition of Bw6+ HLA-B, HLA-A and HLA-C alleles has been obtained. The cloned CD94 molecule covalently assembles with at least two different glycoproteins (43 kDa and 39 kDa) to form functional receptors. NK cells inhibited upon HLA recognition express the CD94/p43 dimer, whose specificity for HLA molecules partially overlaps the Ig-SF receptor system. By contrast, NK clones bearing the homologous CD94/p39 receptor are triggered upon its ligation by CD94-specific mAbs. Remarkably, a set of Ig-SF receptors (p50) homologous to p58 KIRs also display an activating function. CD94-associated molecules belong to the NKG2 family of C-type lectins; the NKG2-A gene encodes for the p43 subunit, which contains cytoplasmic ITIMS. Expression of the different CD94 heterodimeric receptors will enable precise analysis of their putative interaction with HLA class I molecules.

Antigens, CD↗
PubMed1996

Biochemical and serologic evidence for the existence of functionally distinct forms of the CD94 NK cell receptor.

The CD94 NK cell receptor is assembled as a disulfide-linked dimer and appears to be encoded by a single-copy gene of the C-type lectin superfamily. In reverse Ab-dependent cellular cytotoxicity assays, CD94-specific mAbs may either trigger or inhibit cytotoxicity in distinct subsets of NK clones, termed groups A and B, respectively. The molecular basis for this functional ambivalence of CD94 has been addressed. CD94 molecules immunoprecipitated with the HP-3B1 mAb from the two different subsets of NK clones were comparatively analyzed by SDS-PAGE. Under reducing conditions, the stimulating form of CD94 from group A clones displayed a significantly lower Mr (39 kDa) than the inhibitory form of group B clones (Mr = 43 kDa). Analyses of N-glycanase and V8 protease-digested samples indicated that the two CD94 forms are homologous. A CD94-specific mAb (Z199) that did not recognize cells transfected with a CD94 cDNA (LL288) was characterized. Z199 did not bind to group A clones, whereas its reactivity with group B NK cells was indistinguishable from that of other CD94-specific mAbs. Different from the HP-3B1 mAb, the Z199 mAb displayed only inhibitory effects in reverse Ab-dependent cellular cytotoxicity assays. Immunoprecipitation studies confirmed that Z199 selectively identified the 43-kDa CD94. Our study proves the existence of at least two biochemically and serologically distinct CD94 molecules, whose selective/predominant expression at the clonal level correlates with the pattern of response (i.e., inhibition vs activation) of NK cells to ligation by CD94-specific mAbs.

Antigens, CD↗
PubMed1996

Glutamate 94 of [2Fe-2S]-ferredoxins is important for efficient electron transfer in the 1:1 complex formed with ferredoxin-glutamate synthase (GltS) from Synechocystis sp. PCC 6803.

We have analyzed the role of critical amino acid residues involved in the interaction between ferredoxin and ferredoxin-glutamate synthase (GOGAT) encoded by the gltS gene from the cyanobacterium Synechocystis sp. PCC 6803. Our results indicated that the glutamate 94 residue of Anabaena 7120 ferredoxin (= E92 of the Synechocystis 6803 ferredoxin) was necessary for an efficient electron transfer to GOGAT comparable to ferredoxin:NADP-reductase, nitrite reductase and nitrate reductase [Schmitz and Böhme (1995) Biochim. Biophys. Acta 1231, 335-341]. The K(m) value determined for wt-ferredoxins and mutant E94Q (and E92Q) was 1 muM, respectively, and activity loss of E94Q was due to a lowered Vmax. Exchange of residue F65 for aliphatic substitutions, which was crucial to electron transfer to ferredoxin:NADP-reductase and nitrite reductase, exhibited only small effects on glutamate synthase-dependent activity while heterocyst ferredoxin and flavodoxin were almost inactive as electron donors. In contrast to data reported for the spinach system, the stoichiometry of the cross-linked complex between ferredoxin and glutamate synthase was 1:1.

Amino Acid Oxidoreductases↗
PubMed1996

Explaining sex differences in course and outcome in the functional psychoses.

We addressed the following three questions: (i) are there sex differences in outcome in the functional psychoses?, (ii) what is their effect size, and which variables mediate the effect of sex on outcome?, (iii) is the effect of sex diagnosis-specific? In a prospective study of 166 patients with recent onset psychosis, we established that 4-year outcome was more favourable for women. Female patients more often had a remitting illness course (OR = 3.0; 95% CI: 1.5-5.9), were living independently 14% (4-24%) more of the time, had less evidence of negative symptoms over the follow-up period (OR = 0.3; 0.2-0.7) and were more likely to be employed at follow-up (3.6; 1.8-7.6). The findings did not appear diagnosis-specific, although the sample size was small to test for interaction with diagnostic category. Baseline occupational and social adjustment, clinical expression of illness and age and type of onset explained up to 60% of the sex effect. The processes underlying these factors mediate the effect of sex on outcome.

Adolescent↗
PubMed1996

Current role and future perspectives for radiofrequency catheter ablation of postmyocardial infarction ventricular tachycardia.

The most common substrate for ventricular tachycardia (VT) is a postmyocardial infarction (MI) scar. Radiofrequency catheter ablation (RFCA) in post-MI VT faces clinical, electrophysiologic, anatomic, and methodologic difficulties not found in many other human tachycardias. The pathophysiologic understanding of post-MI VT is incomplete; this influences the process of selecting RFCA target sites, which is time consuming, demands catheter stability, and has low sensitivity and predictive value for VT interruption by RF current. Improving and simplifying the methodology of RFCA in post-MI VT is badly needed. We review the pathophysiology of post-MI VT from the data reported on endocardial, epicardial, and intramural ventricular mapping obtained either intraoperatively or in a Langendorff perfused set-up in hearts from transplanted patients. From these studies we conclude that (1) some post-MI VT cases are not amenable to RFCA (reentry around the scar, VT having a subepicardial or deep intramural substrate, or a wide, extensive, subendocardial intrascar area of slow conduction); and (2) searching for the endocardial exit is advantageous for selecting the RFCA targets. We also comment on a new self-reference mapping catheter that allows the recording of high gain, noise-free, unfiltered and filtered unipolar signals as well as unipolar pacing. Among the unresolved issues in these patients is the meaning of fast nonclinical VT induced after successful RFCA of the clinical VT, which may explain why a substantial number of these patients still receive an implantable cardioverter-defibrillator.

Catheter Ablation↗
PubMed1996

Anti-inflammatory effect of a PAF receptor antagonist and a new molecule with antiproteinase activity in an experimental model of acute urate crystal arthritis.

Platelet activating factor (PAF) is a potent mediator of allergic and inflammatory reactions in different pathological conditions. During recent years there has been increasing evidence that PAF can play an important role in the pathogenesis of arthritis. The PMN proteinases make an important contribution to the final tissue joint destruction in arthritis. In a rabbit model of acute crystal arthritis, we have compared the anti-inflammatory effect of two new molecules: BN 50727 with anti-PAF activity, and BN 50548 an inhibitor of PMN proteinases. These molecules were administered dissolved in DMSO at doses of 6 mg/kg three times daily i.p., beginning 24 h before the induction of arthritis. Compared with the untreated animals those receiving the drugs, presented a significant diminution in: (1) the synovial fluid volume; (2) the amount of cells infiltrating the joint cavity and the synovial membrane; and (3) the PGE2 concentration. Furthermore, in both groups of treated rabbits there was a significant decrease in synovial IL-6 concentration and in C-reactive protein serum levels and an important decline of histopathological score. The treatment with BN 50548 induced a significant reduction of TNF levels in the synovial fluid vs DMSO-treated and untreated rabbits. These results further strengthen that in an acute experimental arthritis model, molecules with capacity to antagonize the in vivo action of PAF have an anti-inflammatory effect reflecting an important role for this mediator in the pathogenesis of arthritis. We have also seen that an inhibitor of proteinases is capable of improving the joint inflammation apparently through a decrease in tumor necrosis factor (TNF) and interleukin-6 (IL-6) synovial levels. Furthermore, the proteinase inhibitor treatment preserves the loss of articular proteoglycan content, in an acute arthritis model. In conclusion, BN 50727 and BN 50548, two compounds with PAF antagonist and antiproteinase activity, respectively exert an anti-inflammatory effect in an experimental model of acute urate crystal arthritis, probably due to a decrease in TNF alpha and IL-6 synthesis.

Acute Disease↗
PubMed1996

The cyanobacterial thioredoxin gene is required for both photoautotrophic and heterotrophic growth.

The gene encoding thioredoxin in the facultative heterotrophic cyanobacterium Synechocytis sp. PCC 6803 (trxA) has been cloned by heterologous hybridization using the corresponding gene trxM from the cyanobacterium Anacystis nidulans as a probe. The deduced amino acid sequence of trxA predicts a protein of relative molecular weight of 11,750 and has strong identity with its cyanobacterial counterparts and other m-type thioredoxins of photo-synthetic eukaryotes. The trxA gene has been expressed Escherichia coli as a functional protein of 12 kD and has been shown by western blot analysis to be the same size as in Synechocystis. The trxA gene is transcribed in Synechocystis as a single transcript of 450 nucleotides and accumulates to the same level under photosynthetic and heterotrophic growth conditions. The trxA gene was inactivated with a kanamycin-resistant cassette, and total segregation of the disrupted trxA gene was obtained only when the trxM gene from A. nidulans (E.D.G. Muller, B.B. Buchanan [1989] J Biol Chem 264: 4008-4014) was simultaneously expressed in Synechocytis. Our results suggest an essential role of thioredoxin not only when cells grow photosynthetically but also under heterotrophic conditions.

Amino Acid Sequence↗