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Biomedical subjects

J Martinez

Publications and source records attributed to J Martinez.

At least 199 records · Page 11Linked to original sources

Clinical improvement with fluoxetine therapy and noradrenergic function in patients with panic disorder.

BACKGROUND: Central noradrenergic (NA) dysregulation has provided a major theoretical framework for understanding the pathogenesis of panic disorder (PD). Using clonidine, an alpha 2-adrenergic receptor agonist, as a probe of NA function, we investigated the hypothesis that the antipanic efficacy of the selective serotonin reuptake inhibitors may be associated with normalization of a putatively dysregulated NA system. METHODS: We report further analyses on data from 17 subjects with PD and 16 healthy volunteers who underwent measurement of the plasma NA metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) immediately before and after oral clonidine administration. Thirteen patients with PD were rechallenged after 12 weeks during open fluoxetine hydrochloride treatment using the same clonidine paradigm; 13 healthy volunteers were rechallenged at 12 weeks, not having received treatment between challenges. RESULTS: Patients with PD, compared with healthy volunteers, have markedly elevated plasma MHPG volatility during the first clonidine challenge. Volatility describes the magnitude of within-subject plasma MHPG oscillatory activity as assessed by the root of the mean square successive difference. A greater degree of clinical global improvement was predicted by a greater magnitude of basal MHPG reduction with fluoxetine treatment. Antipanic response to fluoxetine was accompanied by a significant decrease of MHPG volatility to volunteer levels. Volunteer MHPG volatility remained unchanged from the first to second clonidine challenge. CONCLUSIONS: Further evidence is provided for the hypothesis of NA dysregulation in PD as reflected by elevations of within-subjects plasma MHPG volatility during clonidine challenge. Effective selective serotonin reuptake inhibitor-antipanic treatment in this clinical sample was paralleled by normalization of dysregulated NA function.

Adult↗

Normalization of plasma factor X levels in amyloidosis after plasma exchange.

Some patients with systemic light chain amyloidosis develop bleeding complications that can be caused by vascular infiltration with amyloid or by alterations of the coagulation or fibrinolytic systems. Factor X deficiency is the most common cause of bleeding manifestations, although deficiencies of other clotting factors, a disruption in the conversion of fibrinogen to fibrin, and circulating heparin-like anticoagulants have also been reported. Deficiency of factor X is a well-recognized cause of bleeding manifestations in patients with light chain amyloidosis. This acquired disorder appears to be secondary to adsorption of factor X to the amyloid fibrils. Previous studies have shown that infusion of plasma into patients with acquired factor X deficiency and amyloidosis induces a transitory improvement of the coagulation tests. However, there is a rapid return to pretransfusion levels. In this manuscript we report the clinical application of plasma exchange in the management of a patient with systemic light chain amyloidosis with acquired factor X deficiency.

Amyloidosis↗

Effect of glicentin, oxyntomodulin and related peptides on isolated gastric smooth muscle cells.

Glicentin (proglucagon 1-69 GLIC) and oxyntomodulin (proglucagon 33-69 or OXM) are two peptide hormones that are co-released from ileum and large intestine during digestion. They modulate in vivo gastric acid secretion and the gastro-pyloro-duodenal activity. The specificity of their effects is linked to the presence of their C-terminal octapepide. As yet, no isolated target cell that responds specifically to this family of peptides has been described. The present report describes the in vitro effect of human synthetic GLIC, OXM and octapeptide-bearing fragments on smooth muscle cells isolated from the rabbit antrum. GLIC or OXM decreased the mean length of the cells by: 13.9 +/- 0.8% and 15.5 +/- 0.9%, respectively - GLIC being 16 times more potent than OXM (respective EC50 values: 5 and 83 pM). The C-terminal fragments OXM(19-37) and OXM(30-37) were as efficient as GLIC or OXM. Their potencies were OXM = OXM(19-37)>>OXM(30-37). Glucagon, which corresponds to OXM without the C-terminal octapeptide, or glucagon-like peptide-1 (7-36 amide) did not have any effect. The response to OXM was not influenced by antagonists to muscarinic, cholecystokinin or substance P receptors. In conclusion, our studies demonstrate for the first time an isolated target cell that responds specifically to GLIC, OXM and other octapeptide-bearing peptides.

Animals↗

p53 Phosphorylation: biochemical and functional consequences.

The p53 protein plays a vital role in suppressing the development of cancer. Posttranslational modification through phosphorylation has been postulated to be an important regulatory mechanism of p53 function. Data describing the role of phosphorylation in terms of its effects on several biochemical properties and cellular functions of p53 are examined in the context of how p53 might be "phospho-regulated."

Animals↗

Interactions between calcipotriene and ultraviolet light.

BACKGROUND: Calcipotriene is often used with UVB or PUVA, but interactions between UV radiation and calcipotriene have not been examined extensively. OBJECTIVE: Our purpose was to examine interactions between calcipotriene and UV light. METHODS: Minimal erythema doses (MEDs) were determined with UVB and immediate pigment darkening was measured for UVA. The effect of calcipotriene ointment applied before phototesting was examined. Thick and thin applications of calcipotrience were compared. Calcipotriene ointment was applied to a small area on the skin before phototherapy. Patients received either UVB, PUVA, UVA, or no phototherapy. After phototherapy, the ointment was collected and assayed by reverse-phase, high-performance liquid chromatography. RESULTS: MEDs for UVB and immediate pigment darkening for UVA were unaffected by calcipotriene. Thick application of calcipotriene, however, increased the MED, UVA caused substantial reductions in the concentration of detectable calcipotriene. CONCLUSION: When used in conjunction with PUVA, calcipotriene should be applied after exposure to UVA.

Calcitriol↗

Behaviour of metals following intensive pig slurry applications to a natural field treatment process in Brittany (France).

It is well-known that heavy metals brought by intensive pig slurry applications accumulate in the soil; because of their potential impact on the environment, studying their behaviour is of utmost interest. The Solepur process has been developed in Brittany (France) where pig farming causes serious environmental problems; it enables the soil to be used as a treatment medium to process pig slurry. Numerous pig slurry applications were performed from 1991 to 1995 on an experimental hydrologically-isolated field specially equipped to recover all the leachate. These applications approximately corresponded to the amount which might have been spread over one century. The Solepur process can be considered as a simulation model for what happens to metals in pig slurry under normal field conditions over a long period of time. This work measured the concentrations of Cu, Zn, Mn, Co, Fe and Cd in pig slurry, in soil and in drainage water, and the results are discussed. Total concentrations and speciation data within the three different compartments were analysed and showed that Cu and Zn accumulate in the surface layer, whereas other metals, such as Mn and Co, dissolve and are washed away in the leachate. The increase in the bioavailability and toxicity of these metals as well as their impact on the environment are discussed.

Journal Article↗

Inhibition of cyclobutane pyrimidine dimer formation in epidermal p53 gene of UV-irradiated mice by alpha-tocopherol.

Mutations or alterations in the p53 gene have been observed in 50-100% of ultraviolet light (UV)-induced squamous cell carcinoma in humans and animals. Most of the mutations occurred at dipyrimidine sequences, suggesting that pyrimidine dimers in the p53 gene play a role in the pathogenesis of cutaneous squamous cell carcinoma. We previously showed that topical alpha-tocopherol prevents UV-induced skin carcinogenesis in the mouse. In the present study we asked whether topical alpha-tocopherol reduces the level of UV-induced cyclobutane pyrimidine dimers in the murine epidermal p53 gene. Mice received six dorsal applications of 25 mg each of alpha-tocopherol, on alternate days, before exposure to 500 J/m2 of UV-B irradiation. Mice were killed at selected times after irradiation. The level of dimers in the epidermal p53 gene was measured using the T4 endonuclease V assay with quantitative Southern hybridization. Topical alpha-tocopherol caused a 55% reduction in the formation of cyclobutane pyrimidine dimers in the epidermal p53 gene. The rate of reduction of pyrimidine dimers between 1 and 10 hours after irradiation was similar in UV-irradiated mice, regardless of alpha-tocopherol treatment. Therefore, the lower level of cyclobutane pyrimidine dimers in UV-irradiated mice treated with alpha-tocopherol than in control UV-irradiated mice resulted from the prevention of formation of the dimers, and not from enhanced repair of these lesions. Our results indicate that alpha-tocopherol acts as an effective sunscreen in vivo, preventing the formation of premutagenic DNA lesions in a gene known to be important in skin carcinogenesis.

Administration, Cutaneous↗

Congenital dysfibrinogenemia.

Fibrinogen abnormalities can be classified as congenital or acquired. Each class manifests quantitative or qualitative alterations; the latter are known as dysfibrinogenemias. In dysfibrinogenemias, structural defects cause alterations in the conversion of fibrinogen to fibrin. Approximately 300 abnormal fibrinogens have been reported, and about 83 structural defects have been identified. The most common structural defect involve the fibrinopeptides and their cleavage sites, and the second most common involves the gamma-chain polymerization region. Approximately half of the mutants are clinically silent, whereas hemorrhage and thrombosis occur in almost equal numbers of cases. Study of the abnormal fibrinogens has provided insight into fibrinogen structure and fibrin formation and dissolution. Some of the structural abnormalities exhibit defective assembly and activation of components of the fibrinolytic system on the abnormal fibrin, resulting in impaired dissolution of fibrin, clinically associated with thrombosis.

Afibrinogenemia↗

Social work at the emergency department.

We have evaluated the level of satisfaction of patients assigned to a social worker whose role was to give information, support, advice, grief and shock counselling; and develop resource strategies for marginal peoples. Six hundred patients were admitted to the study; 300 of them were supervised by a social worker (group A) and the other 300 were not (group B). After the completion of the study, a questionnaire was sent to be filled in by group A and group B for later evaluation. We collected 200 completed questionnaires (33.3%). The most important areas were: 105 patients (94.5%) in group A vs. 73 patients (82%) (p < 0.005) consider the medical care good or very good. The waiting time was assessed as short or acceptable in 91 patients (81.9%) in group A vs. 55 patients (61.8%) in group B (p < 0.001). The psychosocial care was assessed as very good or good in 101 patients group A (90.9%) vs. 73 patients in group B (82%) (p < 0.5).

Emergency Service, Hospital↗

Occupational allergy in saffron workers.

Sensitization to the flower of saffron, a plant commonly grown in Spain for commercial purposes, and its clinical significance as an occupational allergen were studied. The prick test and RAST, with saffron pollen, stamen, and pistil extracts, were used to evaluate the cutaneous and specific antibody responses in the studied population. Provocation tests in patients with clinical findings were used to verify the implication of saffron components in these symptoms. Fifty saffron workers were evaluated. Three of them were sensitized to saffron pollen and stamen proteins, giving prick and RAST positive values. One patient presented asthma, showing a positive bronchial provocation test, and two patients rhinoconjunctivitis, showing positive conjunctival provocation tests. Of a general allergic population of 237, 10 patients also presented cutaneous test and IgE positive to saffron. Saffron allergens (from pollen and stamens) were characterized by SDS-PAGE immunoblotting. A relevant allergen of 15.5 kDa with profilinic nature was detected and further purified by high-resolution gel filtration chromatography. No allergenic components were demonstrated in pistils. Cross-reactivity of saffron extracts was evaluated by RAST inhibition with respect to other pollen species commonly causing sensitization in the same area of study. A significant degree of cross-reactivity was demonstrated between saffron and Lolium, Salsola, or Olea. The identification of the protein components involved in the cross-reactions was investigated by blot inhibition.

Adolescent↗

Detection and characterization of enterohaemorrhagic Escherichia coli in slaughtered cattle.

Fecal samples from slaughtered cattle were studied for enterohaemorrhagic Escherichia coli (EHEC) by DNA hybridization with biotin-labelled DNA probes specific for the EHEC virulence plasmid, Shiga-like toxin I (SLT I), Shiga-like toxin II (SLT II) and eae gene. Among 136 animals analysed, 47 (34.5%) were found to carry EHEC. The cytotoxic genotypes observed for EHEC strains were: 60.4% SLT I, 12.5% SLT II and 10.4% SLT I + SLT II; 16.7% resulted SLT I and SLT II negative. A total of 14 out of 48EHEC strains (29.2%) hybridized with a fimbrial probe and 14 of 48 strains with an sas probe. An important number of strains (18 out of 48) belonged to serogroups O157, O26 and O111, serogroups also commonly isolated from haemolytic uremic syndrome cases in Chile. While EHEC isolates from the same animal were usually of the same serogroup, one animal was found to carry two EHEC strains of different serogroups. A total of 50% of EHEC strains were sorbitol negative, irrespective of the O serogroup or EHEC genotypic profile. Results obtained in this study strongly suggest that cattle in Chile are a reservoir of EHEC associated with disease in humans.

Abattoirs↗

CholecystokininB receptor from human Jurkat lymphoblastic T cells is involved in activator protein-1-responsive gene activation.

The aim of this study was to analyze the role of cholecystokinin (CCK(B)) receptor in human lymphoblastic Jurkat T cells. We investigated the trophic effect resulting from activation of such a receptor by using the reporter gene strategy. For this purpose, we transiently transfected Jurkat T cells with the reporter plasmid p[(TRE)3-tk-Luc] and found that CCK-8 was able to dose-dependently induce luciferase expression related to activator protein-1 (AP-1) activation with a maximal response identical to that obtained with compounds known to activate AP-1 complex (quantitatively, the same level of induction was obtained with 1 nM 12-O-tetradecanoylphorbol-13-acetate, 100 microM diacylglycerol, or 4 nM epidermal growth factor). The involvement of the CCK(B) receptor in such a stimulation was demonstrated by the inhibiting effect of the selective CCK(B) receptor antagonist PD-135,158. This effect was confirmed in COS-7 cells transfected with the cDNA of CCK(B) receptor cloned from Jurkat T cells. To better understand the AP-1-dependent luciferase expression in Jurkat T cells, we tested two specific inhibitors of serine/threonine phosphatases-1 and -2A: okadaic acid and calyculin A. These compounds strongly increased the phorbol-12-myristate-13-acetate response, whereas we have not observed a contribution of phosphatase inhibitors on a CCK-8-induced luciferase activity. To confirm that CCK(B) receptors are involved in AP-1 response, we investigated the CCK-8 effect on interleukin-2 expression, a natural endogenous gene regulated by several factors, including AP-1. In Jurkat T cells activated by phorbol-12-myristate-13-acetate and phytohemagglutinin, CCK-8 induced IL-2 expression. This induction was abolished by PD-135,158. Our results indicate that CCK-8 exerts a trophic effect in Jurkat T cells through stimulation of CCK(B) receptors by modulation of expression of AP-1-regulated genes.

Animals↗

Role of prostaglandin H synthase-2-mediated conversion of arachidonic acid in controlling 3T6 fibroblast growth.

The specific role(s) of arachidonic acid (AA) and its metabolites in the signaling pathways that regulated fibroblast growth was studied. A Western blot analysis demonstrated that prostaglandin H synthase-2 (PGHS-2) was expressed by 3T6 fibroblast cultures in RPMI 1640 supplemented with fetal calf serum (10%). Dexamethasone, which inhibits AA release and PGHS-2 expression, significantly reduced cell proliferation. Ketoprofen, a dual cyclooxygenase inhibitor, and CGP-28238, a specific PGHS-2 inhibitor, reduced fibroblast proliferation in a dose-dependent manner. These drugs also reduced [3H]thymidine incorporation into the DNA of fibroblasts. These effects were correlated with a decrease in prostaglandin (PG) E2 levels in the cell medium. However, piroxicam at doses that selectively inhibit PGHS-1 did not have a significant effect on fibroblast proliferation. Finally, we showed that the antiproliferative effect of dexamethasone and PGHS-2 inhibitors was significantly antagonized when PGE2 was added to the culture medium. Our results suggest that PGHS-2 and prostaglandins such as PGE2 might play an important role in the regulation of 3T6 fibroblast growth stimulated by growth factors of serum.

3T3 Cells↗

A new biological contribution of cyclo(His-Pro) to the peripheral inhibition of pancreatic secretion.

The tripeptide pyro-Glu-His-Pro-NH2[thyrotropin-releasing hormone (TRH)] was isolated from the hypothalamus as a thyrotropin-releasing factor. It has a broad spectrum of central nervous system-mediated actions, including the stimulation of exocrine pancreatic secretion. TRH is also synthesized in the endocrine pancreas and found in the systemic circulation. Enzymatic degradation of TRH in vivo produces other bioactive peptides such as cyclo(His-Pro). Because of the short half-life of TRH and the stability of cyclo(His-Pro) in vivo, we postulated that at least part of the peripheral TRH effects on the exocrine pancreatic secretion may be attributed to cyclo(His-Pro), which has been shown to have other biological activities. This study determines in parallel the peripheral effects of TRH and cyclo(His-Pro) as well as the putative contribution of other TRH-related peptides on exocrine pancreatic secretion in rats. TRH and its metabolite cyclo(His-Pro) dose dependently inhibited 2-deoxy-D-glucose (2-DG)-stimulated pancreatic secretion. TRH and all the related peptides tested had no effect on the basal and cholecystokinin-stimulated amylase release from pancreatic acinar cells in vitro. These data indicate that cyclo(His-Pro) mimics the peripheral inhibitory effect of TRH on 2-DG-stimulated exocrine pancreatic secretion. This effect is not detected on isolated pancreatic acini. Our findings provide a new biological contribution for cyclo(His-Pro) with potential experimental and clinical applications.

Amylases↗