Bifunctional enzyme 6'-N-aminoglycoside acetyltransferase-2"-O-aminoglycoside phosphotransferase in Lactobacillus and Pediococcus isolates of animal origin.
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Acetyltransferases↗
Biomedical subjects
C Martinez
Publications and source records attributed to C Martinez.
Immunology of VIP: a review and therapeutical perspectives.
Vasoactive intestinal peptide (VIP) is a neuropeptide with a broad distribution in the body that exerts very important pleiotropic functions in several systems. The present work reviews the immunology of VIP. Being daring, this neuropeptide could be included in the group of cytokines since it is produced and secreted by different immunocompetent cells in response to various immune signals, plays a broad spectrum of immunological functions, and exerts them, in a paracrine and/or autocrine way, through three different specific receptors. Although VIP has been classically considered as an immunodepressant agent, and its main described role has been as an anti-inflammatory factor, several evidences suggest that a better way to see this peptide is as a modulator of the homeostasis of the immune system. In the last decade, the pharmacology of VIP has spectacularly grown, and VIP itself, as well as more stable VIP-derived agents, have been used or proposed as efficient therapeutical treatments of several disorders, specially inflammatory and autoimmune diseases, such as septic shock, rheumatoid arthritis, multiple sclerosis, Crohn's disease and autoimmune diabetes. A broad field of perspectives is actually open, and further investigations will help us to definitively understand the immunology of this very important peptide.
Animals↗
Insulin-dependent phosphorylation of a 70-kDa protein in light microsomes from rat adipocytes.
In order to discover possibly novel insulin receptor substrates and/or downstream targets in the insulin signaling pathway, we established a cell-free system for this purpose using purified insulin receptor and subcellular fractions from rat adipocytes as a sourse of cellular substrates. Under these conditions, we have found a 70-kDa protein (pp70) in fat cells that is tyrosine-phosphorylated by the activated insulin receptor. Using sucrose velocity gradient sedimentation we also show that pp70 cofractionate a particulate fraction containing IRS-1 but not with GLUT-4 vesicle-enriched fractions. Our results suggest that pp70 may be an endogenous substrate for the insulin receptor tyrosine kinase.
3T3 Cells↗
Separating the retinal electrophysiologic effects of vigabatrin: treatment versus field loss.
OBJECTIVE: To separate the retinal electrophysiologic markers associated with vigabatrin-attributed visual field loss (VGB-VFL) from those associated with current vigabatrin therapy. METHODS: A nonrandomly selected cohort of 8 previous and 18 current vigabatrin users and a reference cohort of 8 never vigabatrin-treated patients with epilepsy receiving other antiepilepsy drugs (AED) underwent electro-oculography (EOG), electroretinography (ERG), and automated static threshold perimetry. A cohort of 22 normal subjects underwent ERG. The validity of the retinal electrophysiologic variables to detect the presence and severity of VGB-VFL was assessed using receiver operator characteristic curves. RESULTS: Of 26 patients exposed to vigabatrin, 18 exhibited VGB-VFL. No patients receiving alternative AED showed this type of visual field abnormality. The presence and severity of VGB-VFL was significantly associated with the latency (implicit time) and amplitude of the ERG cone function. The amplitude of the cone flicker response was the strongest predictor of VGB-VFL and revealed a sensitivity of 100% at a specificity of 75%. The EOG, the photopic and scotopic ERG, and the latency of the ERG second oscillatory potential (OP2) were not significantly related to the presence of VGB-VFL. Vigabatrin therapy was significantly associated with the photopic amplitude, the scotopic a-wave latency, and the latency of OP2. CONCLUSION: In patients who cannot perform reliable perimetry, the cone-specific ERG flicker amplitude provides the best screening method for detecting VGB-VFL.
Adult↗
Anti-inflammatory properties of the type 1 and type 2 vasoactive intestinal peptide receptors: role in lethal endotoxic shock.
Vasoactive intestinal peptide (VIP) is a neuropeptide that can modulate several immune aspects. Previous reports showed that VIP attenuates the deleterious consequences of septic shock by inhibiting the production of pro-inflammatory agents and stimulating the production of anti-inflammatory cytokines in activated macrophages. In this study, by using selective VIP agonists, we investigated the differential involvement of the VIP receptors in the anti-inflammatory role of VIP. Both the type 1 VIP receptor (VPAC1) agonist, [K(15), R(16), L(27)] VIP 1-7-GRF 8-27, and the type 2 VIP receptor (VPAC2) agonist, Ro25-1553, protected mice from lethal endotoxemia by inhibiting the macrophage-derived pro-inflammatory mediators IL-6, TNF-alpha, IL-12 and NO, and by stimulating the production of the anti-inflammatory cytokine IL-10. In addition, both VIP and VPAC1 agonist, but not the VPAC2 agonist, reduced in vitro and in vivo the expression of the co-stimulatory B7. 1/B7.2 molecules, and the subsequent stimulatory activity for T helper cells in stimulated macrophages. The higher effectiveness of the VPAC1 agonist compared with the VPAC2 agonist suggests that VPAC1 is the major mediator of the anti-inflammatory action of VIP. Since VIP and the two agonists appear to affect multiple cytokines and inflammatory factors, they might provide a more efficient therapeutical alternative to the use of specific cytokine antibodies or antagonists.
Animals↗
Separating the retinal electrophysiologic effects of vigabatrin. treatment versus field loss
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Journal Article↗
Types of fat intake and body mass index in a Mediterranean country.
BACKGROUND: Although the fatty acid fractions provide similar metabolizable energy, the type of dietary fat consumed could be relevant to the development of obesity. OBJECTIVE: To investigate the relationship between body mass index (BMI), obesity and the consumption of different types of fat and olive oil in a Mediterranean country with high prevalence of obesity, and high intake of monounsaturated fatty acids (MUFA) and olive oil. SUBJECTS: The study was carried out in Spain among 23 289 women and 14 374 men, aged 29-69 years, who were participants of a large European prospective cohort. METHODS: : Information on usual food intake was collected by interviewers by means of a dietary history questionnaire. The association between obesity (BMI >/= 30 kg m2), dietary fat, other dietary patterns and other non-dietary factors were tested using multilinear regression analysis. The ratio of reported energy intake to energy requirement was used as an estimation of dietary underreporting. RESULTS: The association between fatty acid fractions intake (saturated fatty acids (SFA) in women, and MUFA and polyunsaturated fatty acids (PUFA) in both sexes) and BMI was very weak, accounting for less than 1% of variance. All dietary and non-dietary variables accounted for 21% of variance in the measurement of BMI in women and only 6.7% of variance in men. Estimated underreporting of energy intake was 17.5% in obese women and 5.5% in obese men. CONCLUSIONS: The association between consumption of specific types of dietary fat, olive oil and obesity in Spain is not very important. However, because of the cross-sectional design and some level of underreporting of energy intake observed in overweight subjects and overreporting in underweight subjects, systematic bias cannot be completely discarded.
Adipose Tissue↗
Mobilization kinetics of peripheral blood progenitor cells after IAPVP-16 salvage chemotherapy plus G-CSF in lymphoproliferative disorders.
We have explored the efficacy of salvage chemotherapy combination, IAPVP-16 (ifosfamide 5 g/m2 on day 1; VP-16 100 mg/m2 on days 1-3; ara-C 1.2 g/m2/12 h on days 1 and 2; methylprednisolone 80 mg/m2 on days 1-5) plus G-CSF for PBPC mobilization. This protocol was used in 45 patients with relapsed or refractory lymphoproliferative diseases who underwent 85 leukaphereses. In 41 patients > 2 x 106/kg CD34+ cells were obtained after a median of two procedures. The median number of CD34+ cells harvested was 3.2 x 106/kg per apheresis and 8.4 x 106/kg per patient. Seven of 10 patients who had failed previous mobilization attempts achieved more than 2 x 106 CD34+ cells/kg in a maximum of three aphereses. A history of previous mobilization failure and a low platelet count (<150 x 109/l) negatively influenced the CD34+ cell yield in univariate and multivariate analyses. A good correlation was found between the circulating CD34+ cells/microl and the CD34+ cells and CFU-GM in the leukaphereses products (r = 0.93 and r = 0.73, P < 0.001), and > or =17 CD34+ cells/microl predicted the achievement of > 2 x 106/kg CD34+ cells in a single leukapheresis in more than 90% of cases. IAPVP-16 plus G-CSF may be specially indicated in tandem transplantations or CD34+ selection and in patients who have failed previous mobilization attempts.
Adult↗
Neuroregulation of growth hormone during exercise in children.
Physical exercise is an important physiological stimulus to growth hormone (GH) release in man. Many neurotransmitters are involved in GH regulation. We studied the effect of the cholinergic pathway on GH secretion induced by physical exercise. Particularly, we studied the effect of a cholinergic muscarinic agonist on GH-induced physical exercise, both in children and adults. Moreover, we investigated the refractoriness of GH secretion after a second physical exercise stimulus. Three different protocols were performed: 1) GH response to physical exercise in children and adults; 2) effect of pyridostigmine on exercise-induced GH secretion in children and adults; 3) GH response to two consecutive exercises in children and adults. Our data show that in children GH peak after physical exercise is higher than in adults. Pyridostigmine enhances GH release in children and in adults. Exercise stimulus was able to release GH in the second test only in children, while the refractory phase did not permit a new GH release in adults. The shift to a modality of neural control of GH secretion peculiar of adults is likely due to neuroregulatory mechanisms which may be partly dependent on long-term variation in hormonal milieu.
Adolescent↗
Salicylic acid mediated by the oxidative burst is a key molecule in local and systemic responses of cotton challenged by an avirulent race of Xanthomonas campestris pv malvacearum.
We analyzed the production of reactive oxygen species, the accumulation of salicylic acid (SA), and peroxidase activity during the incompatible interaction between cotyledons of the cotton (Gossypium hirsutum) cv Reba B50/Xanthomonas campestris pv malvacearum (Xcm) race 18. SA was detected in petioles of cotyledons 6 h after infection and 24 h post inoculation in cotyledons and untreated leaves. The first peak of SA occurred 3 h after generation of superoxide (O(2)(.-)), and was inhibited by infiltration of catalase. Peroxidase activity and accumulation of SA increased in petioles of cotyledons and leaves following H(2)O(2) infiltration of cotyledons from 0.85 to 1 mM. Infiltration of 2 mM SA increased peroxidase activity in treated cotyledons and in the first leaves, but most of the infiltrated SA was rapidly conjugated within the cotyledons. When increasing concentrations of SA were infiltrated 2. 5 h post inoculation at the beginning of the oxidative burst, the activity of the apoplastic cationic O(2)(.-)-generating peroxidase decreased in a dose-dependent manner. We have shown that during the cotton hypersensitive response to Xcm, H(2)O(2) is required for local and systemic accumulation of SA, which may locally control the generation of O(2)(.-). Detaching cotyledons at intervals after inoculation demonstrated that the signal leading to systemic accumulation of SA was emitted around 3 h post inoculation, and was associated with the oxidative burst. SA produced 6 h post infection at HR sites was not the primary mobile signal diffusing systemically from infected cotyledons.
Amitrole↗
Receptors and transcriptional factors involved in the anti-inflammatory activity of VIP and PACAP.
VIP and PACAP modulate the function of inflammatory cells through specific receptors. VIP/PACAP inhibit the production of TNF alpha, IL-6, IL-12, and nitric oxide (NO), and stimulate IL-10 in peritoneal macrophages and Raw 264.7 cells. Here we report on the specific VIP/PACAP receptors, transduction pathways, and transcriptional factors involved in the regulation of these macrophage factors by VIP and PACAP. Both neuropeptides inhibit IL-6 production mainly through PAC1 binding, PKC activation, and the subsequent shedding of the LPS receptor CD14 in macrophages. However, the effects on TNF alpha, IL-10, IL-12, and NO are mostly mediated through the constitutively expressed VPAC1 receptor, although the inducible expressed VPAC2 may also participate. VIP/PACAP binding to VPAC1 induces both a cAMP-dependent and a cAMP-independent pathways that regulate cytokine and NO production at the transcriptional level. VIP/PACAP inhibit TNF alpha through reduction in NFkB binding and changes in the composition of CRE-binding complexes; they inhibit IL-12 through reduction in NFkB binding and changes in the composition of the ets-2 complexes. VIP/PACAP inhibit iNOS expression through reduction in NFkB and IRF-1 binding, and augment IL-10 by increasing CREB-binding. Whereas the inhibition of IRF-1 and CRE-binding complexes seems to be mediated through the cAMP-dependent pathway, VIP/PACAP inhibition of NFkB nuclear translocation is mediated through a reduction in IkB alpha degradation mediated by the cAMP-independent pathway. This study provides new evidence for the understanding of the molecular mechanism by means of which VIP and PACAP attenuate the inflammatory response.
Animals↗
Anti-inflammatory actions of VIP/PACAP. Role in endotoxemia.
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Animals↗
[Clinical case of the month. An unusual presentation of superior vena cava syndrome].
We report the case of a 48-year-old man who was admitted to our emergency department because of a superior vena caval syndrome from which the symptoms occurred only during exercise. His past history included an episode of lower limb deep venous thrombosis. Because an atrio-ventricular partial block was fortuitously evidenced, the patient was submitted to a pacemaker insertion. A few years later, the patient suffered from rapid dyspnea on exercise, associated with facial cyanosis and systemic hypotension. The exploration by phlebography evidenced that the inferior vena cava was completely obstructed. Therefore the venous return from the lower part of the body to right heart was obtained through hypertrophy of the vena azygos. In addition, the presence of cardiac pacing electrodes induced a stenosis at the level of the superior vena cava, just before its entrance into the right atrium. Such a venous network accounted for the occurrence of a chronic superior vena caval syndrome associated with peripheral arterial hypotension during exercise. Treatment consisted of a superior vena caval percutaneous transluminal balloon angioplasty followed by a Wallstent insertion. This procedure led to a correction of all hemodynamic abnormalities responsible for reported pathophysiological limitations to stress.
Angioplasty, Balloon, Coronary↗
Shedding of membrane-bound CD14 from lipopolysaccharide-stimulated macrophages by vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide.
Macrophage activation and deactivation play essential roles in the initiation and maintenance of a successful immune response. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP), two structurally related neuropeptides, act as macrophage deactivating factors. We reported previously that VIP and PACAP inhibit IL-6, IL-12, TNF alpha and NO production, and enhance IL-10 production, from lipopolysaccharide (LPS)-stimulated macrophages. In this study, we demonstrate that VIP and PACAP down-regulate the expression of CD14, the membrane-bound LPS receptor, by inducing its rapid shedding. The soluble CD14 released by VIP and PACAP corresponds in size to the soluble CD14 released by PMA. Neither VIP/PACAP nor PMA, affect the steady-state levels of CD14 mRNA. The CD14 shedding induced by VIP/PACAP is mediated through the PAC1 specific receptors and the major transduction pathway involves the protein kinase C (PKC). The VIP/PACAP inhibition of TNF alpha and NO occurs through both CD14-dependent and -independent mechanisms, whereas the inhibition of IL-6 production appears to be strictly CD14-dependent. The shedding of CD14 by VIP and PACAP represents an important mechanism by which these neuropeptides limit the macrophage inflammatory response.
Animals↗
A new potent antigen from Echinococcus granulosus associated with muscles and tegument.
An immunoscreening of a cDNA library derived from the adult stage of the parasitic platyhelminth Echinococcus granulosus has been carried out with sera from infected dogs. The EgA31 clone encodes a fibrous protein which shares some sequence elements with paramyosins. The corresponding gene is present as a single copy in the genome. As revealed by an antibody obtained against a fusion protein produced in bacteria, the polypeptide has a molecular weight of 66 kDa. This polypeptide is present at all developmental stages studied and is a potent antigen during an infection by the adult stage in the dog and during cyst growth in human patients. By immunohistology, it was shown that it is present in the tegument and subtegumental parenchyma of the adult with a main location in the region of the suckers where it rapidly accumulates at the time of the head evagination. It is also present in the germinal layer of the cyst and on the protoscolex.
Amino Acid Sequence↗
Incidence of tumor-cell contamination in leukapheresis products of breast cancer patients mobilized with stem cell factor and granulocyte colony-stimulating factor (G-CSF) or with G-CSF alone.
We have assessed tumor contamination of peripheral blood progenitor cells (PBPC) in 203 high-risk breast cancer patients who were prospectively randomized to mobilization with stem cell factor (SCF) plus granulocyte colony-stimulating factor (G-CSF) versus G-CSF alone. The patients then received high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) with PBPC support. One bone marrow aspirate obtained before treatment, one whole blood specimen obtained before cytokine infusion, and one to five leukapheresis products were tested for the presence of tumor cells by an alkaline phosphatase immunocytochemical technique with a targeted sensitivity of 1.7 tumor cells per 10(6) hematopoietic cells. Tumor cells were detected in the bone marrow, peripheral blood, and/or PBPC of 21 patients (10%). In 14 patients, bone marrow specimens were tumor-positive; in seven patients, premobilization whole blood specimens were tumor-positive, and in eight patients, leukapheresis products were tumor-positive. In five patients, repetitive or multiple specimens were tumor-positive, and in three cases, marrow, peripheral blood, and PBPC products were all tumor-positive. Nine of the patients in whom tumor cells were found in marrow or peripheral blood were clinical stage II to III and 12 were clinical stage IV. Nine of the tumor-positive patients were in the SCF + G-CSF arm and 12 were in the G-CSF arm. Tumor cells were detected in leukapheresis products of eight patients: three in the G-CSF + SCF arm and five in the G-CSF arm. We conclude that detectable tumor-cell contamination of bone marrow, peripheral blood, and/or PBPC occurred in approximately 10% of patients in this trial and was observed in stage II to III patients, as well as in stage IV patients. No significant difference could be found in the rate of PBPC tumor-cell contamination between patients who received SCF + G-CSF compared with those who received G-CSF alone. Neither mobilization regimen was found to increase the rate of tumor-cell contamination when control premobilization blood samples were compared with leukapheresis products.
Breast Neoplasms↗
Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit endotoxin-induced TNF-alpha production by macrophages: in vitro and in vivo studies.
Vasoactive intestinal peptide (VIP) is a neuropeptide synthesized by immune cells that can modulate several immune aspects, including the function of cells involved in the inflammatory response, such as macrophages and monocytes. The production and release of cytokines by activated phagocytes are important events in the pathogenesis of ischemia-reperfusion injury. There is abundant evidence that the proinflammatory cytokine TNF-alpha is an important mediator of shock and organ failure complicating Gram-negative sepsis. VIP has been shown to attenuate the deleterious consequences of this pathologic phenomenon. In this study we have investigated the effects of VIP and the structurally related neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38) on the production of TNF-alpha by endotoxin-activated murine peritoneal macrophages. Both neuropeptides rapidly and specifically inhibit the LPS-stimulated production of TNF-alpha, exerting their action through the binding to VPAC1 receptor and the subsequent activation of the adenylate cyclase system. VIP and PACAP regulate the production of TNF-alpha at a transcriptional level. In vitro results were correlated with an inhibition of both TNF-alpha expression and release in endotoxemic mice in vivo. The immunomodulatory role of VIP in vivo is supported by the up-regulation of VIP release in serum and peritoneal fluid by LPS and proinflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6. These findings support the idea that under toxicity conditions associated with high LPS doses, VIP and PACAP could act as protective mediators that regulate the excessive release of TNF-alpha to reduce inflammation or shock.
Animals↗