PubMed Health⌕ Search

Biomedical subjects

L Perez

Publications and source records attributed to L Perez.

At least 19 recordsLinked to original sources

NMR and cDNA array analysis prior to heart failure reveals an increase of unsaturated lipids, a glutamine/glutamate ratio decrease and a specific transcriptome adaptation in obese rat heart.

Obesity is a risk factor for heart failure through a set of hemodynamic and hormonal adaptations, but its contribution at the molecular level is not clearly known. Therefore, we investigated the kinetic cardiac transcriptome and metabolome in the Spontaneous Hypertensive Heart Failure (SHHF) rat. The SHHF rat is devoid of leptin signaling when homozygous for a mutation of the leptin receptor (ObR) gene. The ObR-/- SHHF rat is obese at 4 months of age and prone to heart failure after 14 months whereas its lean counterpart ObR-/+ is prone to heart failure after 16 months. We used a set of rat pangenomic high-density macroarrays to monitor left ventricle cardiac transcriptome regulation in 4- and 10-month-old, lean and obese animals. Comparative analysis of left ventricle of 4- and 10-month-old lean rat revealed 222 differentially expressed genes while 4- and 10-month-old obese rats showed 293 differentially expressed genes. (1)H NMR analysis of the metabolome of left ventricular extracts displayed a global decrease of metabolites, except for taurine, and lipid concentration. This may be attributed to gene expression regulation and likely increased extracellular mass. The glutamine to glutamate ratio was significantly lower in the obese group. The relative unsaturation of lipids increased in the obese heart; in particular, omega-3 lipid concentration was higher in the 10-month-old obese heart. Overall, several specific kinetic molecular patterns act as a prelude to heart failure in the leptin signaling deficient SHHF obese rat.

Adaptation, Biological↗

Identification of selective inhibitors of VHSV from biased combinatorial libraries of N,N'-disubstituted 2,5-piperazinediones.

A combinatorial strategy has been used to design and identify inhibitors of viral haemorrhagic septicemia virus (VHSV), a salmonid rhabdovirus of economic importance. Two libraries of N,N'-disubstituted 2,5-piperazinediones (DKP), DKP-I and DKP-II were screened for inhibition of VHSV infectivity. Among the 98 DKP-derivatives (R1-DKP-R2) screened, a novel class of VHSV in vitro inhibitors was identified. Evidences are presented showing that the selected DKP-derivatives cause dose-dependent inhibition of VHSV infectivity in the absence of cellular toxicity. Preliminary characterization of its inhibition mechanism ruled out direct inactivation of the virus (virucidal effect) or interference with early viral replication steps. Furthermore, analysis of infection foci sizes, virus titers, viral protein accumulation and presence of cell free virus derived from VHSV-infected cell cultures in the presence of DKP-derivates suggested that virus assembly/release was impaired leading to a reduced virus spread in cell culture. New DKP-derivatives with a significant higher specific activity need to be developed to start testing its possible practical use but the selected DKP-derivatives described here may contribute to their further development as well as being tools to improve our knowledge on the fish rhabdovirus infection cycle.

Antiviral Agents↗

Stable expression of bioactive recombinant pleurocidin in a fish cell line.

Pleurocidin (Ple), a linear cationic peptide of 25 amino acids, is a member of a larger family of antimicrobial peptides present in flatfish. Previous studies have shown that Ple displays a strong antimicrobial activity against a broad spectrum of bacteria and appears to play a role in innate host defence. In this work, the genomic sequence encoding the Ple prepropeptide has been isolated from Limanda limanda and cloned in a vector under the control of a non-viral promoter (the carp beta-actin promoter). By using this construction, expression of bioactive Ple was demonstrated in transformed fish cell lines continuously growing for more than 2 years. Furthermore, the study of Ple processing, maturation and secretion (by using fusion with green fluorescence protein) and the high bactericidal activity of the secreted recombinant Ple (detectable in cell supernatants without any concentration) are all reported here, as no other recombinant Ple or fish antimicrobial peptide have been expressed before to that extent. Such an overexpression of recombinant Ple or any other related antimicrobial peptide might improve the chances to develop new antibiotic agents, as well as to provide essential information about the mechanism of action, range of activity and the role in the innate immune response of antibiotic peptides.

Amino Acid Sequence↗

Pulp cell cultures obtained with two different methods for in vitro cytotoxicity tests.

AIM: To describe two different protocols for obtaining primary pulp cell cultures, one derived from explants and the other following dissociation into single cell suspension by enzyme digestion. METHODS: Human pulp tissue was obtained from three healthy premolars. The harvested pulp tissue was prepared for culture using physical methods (one of the premolars) and enzyme, type XI collagenase, (the two remaining premolars). RESULTS: In the case of explant based culture, only limited growth was observed in some cases. However, by enzyme digestion, after two weeks cell growth was evident, and differences in cell type were observed according to the tooth involved. CONCLUSION: It has been possible to obtain abundant biological material using an enzyme digestion-based protocol for testing purposes, with low experimental variability, as all cells originated from the same individual.

Cell Culture Techniques↗

No association of apolipoprotein E epsilon4 genotype with faster progression or less recovery of relapses in a Spanish cohort of multiple sclerosis.

BACKGROUND: Recent data have suggested a faster deterioration of multiple sclerosis (MS) patients who harbour the epsilon4 allele of the apolipoprotein E (APOE) gene. We investigate the relationship of APOE genotypes with disease severity and clinical recovery of relapses in a MS population of the north of Spain. METHODS: One hundred and thirty-three patients with clinically defined MS were studied. Disease course (relapsing versus progressive), age of onset, duration of the disease and disability measured by the Expanded Disability Status Scale (EDSS) were recorded. Worsening was measured by the Progression Index (PI) and by EDSS 4 and 6 latencies. In 79 patients with relapsing-remitting (RR) MS the degree of clinical recovery of relapses (total versus partial) was assessed. RESULTS: The frequency of the APOE epsilon4 allele in our patients was similar to that found in other southern European populations. APOE epsilon4 patients did not have a faster progression as assessed by PI and EDSS 4 and 6 latencies. Among 79 patients with RRMS there were no significant differences in the degree of recovery of relapses. CONCLUSIONS: In this MS population, APOE epsilon4 polymorphism is not associated with a more severe clinical course and does not appear to influence recovery of exacerbations.

Adult↗

[Invasive schistosomiases].

Schistosomiasis is a tropical helminthic infection, observed in travelers as well as local populations. It is most often due to Schistosoma mansoni or Schistosoma haematobium and can be diagnosed at the invasive phase. Migration of the schistosomulae (larvae) in the body leads to acute parasitic toxemia, which includes a hypersensitivity reaction and circulating immune complexes. The invasive stage occurs generally 2 to 6 weeks after the exposure and combines fever, asthenia, faintness and headaches. Other signs include diarrhea, dry cough, dyspnea, urticarial rash, arthralgia, myalgia, and enlargement of liver and spleen. Although rare, neurological and cardiac complications may be fatal. This diagnosis should be considered in travelers returning from the tropics with compatible clinical signs and delayed hypereosinophilia, if they report exposure in an endemic area. It is later confirmed by seroconversion for schistosomiasis and then by observation of schistosome eggs in stool or urine (according to species). The standard treatment of acute schistosomiasis with praziquantel is ineffective and can aggravate clinical outcome during this phase. Corticosteroid treatment is recommended for serious forms with neurological or cardiac manifestations.

Acute Disease↗

Comparative analysis of CD1a, S-100, CD83, and CD11c human dendritic cells in normal, premalignant, and malignant tissues.

A number of antibodies that recognize human dendritic cells (DC) have been identified. The main aim of this study was to compare and contrast different antigen retrieval techniques using both enzymatic and non-enzymatic treatments in order to determine the expression and distribution of several DC markers on formalin-fixed, paraffin-embedded tissues. Normal human lung, oral epithelial hyperplasia lesions, oral squamous cell carcinoma, and prostate adenocarcinoma tissues were evaluated using a panel of DC specific antibodies. The results of immunohistochemical staining for CD83, CD1a, CD11c, and S-100 DC markers were compared following the different antigen retrieval approaches. The overall best results for the analysis of tumor-associated DC were obtained with the enzymatic methods. Protease XXIV digestion was determined to be essential for detection of S-100 and CD11c positive DC, whereas trypsin and pepsin were required for the recognition of CD1a and CD83 expressing tumor-associated DC. These results could be easily adapted for routine practice and should be useful for characterization of the DC system in cancer patients for both diagnostic and prognostic purposes. In addition, standardized procedures for evaluating different subpopulations of tumor-associated DC should bring new insights in understanding of DC-tumor cell interaction.

Antigens, CD↗

[A group fever: safari's fever].

INTRODUCTION: Acute schistosomiasis, called safari's fever in Africa and Katayama fever in Japan, is an immunoallergic reaction due to transcutaneous penetration of infective cercaria. We report the collective case of seven young adults spending holidays in Mali. EXEGESIS: An eighteen years-old girl presents fever, headache, diarrhoea and abdominal pains at return from Dogon country (south of Mali). After turned down malaria and with the notion of bathing in fresh water followed by pruritus, we think to safari's fever. So we alarm all other members of the group. All can be treated to avoid chronic schistosomiasis. CONCLUSION: These observations recall that acute schistosomiasis is a real danger for tourists when bathing in fresh water in endemic areas of Africa. Education of travellers is necessary. Occurrence of safari's fever should alert physicians to prevent chronic schistosomiasis.

Adolescent↗

The status of Spain's dental practices following the European Union directive concerning radiological installations.

OBJECTIVES: To assess the influence of new European Union (EU) legislation on dental radiology practices and the reduction in patient radiation exposure. STUDY DESIGN: A total of 7176 official reports from Spanish dental offices or clinics covering the period 1996 to 2001 were analyzed. RESULTS: Of the dental radiological installations inspected in 2001, 72.79% used the kilovoltage recommended by the EU (70 kVp) and 98.85% used at least 1.5 mm Al filtration. At least 90.11% of the installations had a focal film distance of 20 cm although there were no cases with a rectangular collimator as adapted to the size of film. Thirty percent of the installations showed a mechanical fault every year. In 17.62% of cases the radiological film was stored in the exposure room. Few clinics (10.24%) used high-speed films and only 11.95% of clinics employed digital systems. The mean dose received by patients fell during the 5 years studied by 18.75%. Radiological equipment fulfilling the EU specifications emitted significantly lower doses than other nonapproved equipment. CONCLUSIONS: The introduction of legislation has resulted in a gradual improvement in dental radiology practices.

Analysis of Variance↗

Coping styles among families of children with HIV infection.

The primary aim of this study was to examine coping strategies among families of HIV-infected children and how they relate to medical, central nervous system (CNS) and family environment factors. Caregivers of HIV-positive children (N=52) completed a family coping measure (F-COPES) and provided information regarding family environment. Data regarding medical and CNS status were obtained from patient records. Results indicated that families' passive coping and spiritual support were among the coping techniques used most often, and social support was used least often. Medical variables were unrelated to any coping styles. Families of children with CNS impairment endorsed more passive coping techniques than families of children with no apparent deficits. A trend was found for non-biological caregivers to seek out more community resources and support than biological caregivers. Findings suggest the need to target families least likely to utilize resources, and to teach them to effectively seek out and benefit from social and community supports.

Adaptation, Psychological↗

Reversible inhibition of spreading of in vitro infection and imbalance of viral protein accumulation at low pH in viral hemorrhagic septicemia rhabdovirus, a salmonid rhabdovirus.

The inhibition of viral hemorrhagic septicemia rhabdovirus (VHSV) in vitro infection by pHs of <7 (low pH) has been previously reported. Nevertheless, the details of the mechanism underlying this effect remain obscure. We present evidence showing that low-pH inhibition occurs during a viral postadsorption step. Thus, while VHSV bound, replicated within single cells, and presented its G protein on the membranes of infected cells at both low and physiological pHs, both cell-to-cell spreading of infection (as estimated by the appearance of foci of infected cells) and fusion (as estimated by a syncytium assay) were inhibited by this low pH. The decreased VHSV titers and the inhibition of both cell-to-cell spreading of infection and fusion could be reversed by adjusting the pH to 7.5 at any time during infection. This effect should be taken into account to avoid false negatives in the diagnosis of VHSV by cell culture. On the other hand, the cell-to-cell spreading of infection at pH 7.5 could be stopped at any time by reducing the pH to 6.5. Since at low pH there were changes in the protein G conformation and smaller and imbalanced amounts of N with respect to M1, M2, and G viral proteins, alterations of the assembly and/or budding of VHSV are most probably involved in the absence of newly released infective virions.

Animals↗

Antibody response to a fragment of the protein G of VHS rhabdovirus in immunised trout.

A fragment (called frg#11, amino acids, aa 56-110) of the protein G (pG) of viral haemorrhagic septicaemia virus (VHSV) was designed after previous results showed it to be recognised by approximately 40% of the trout immunised to VHSV [Dis. Aquat. Organ. 34 (1999) 167]. frg#11 was then cloned, expressed, purified and used to study the production of antibodies to its epitopes in trout immunised to VHSV. Anti-frg#11 trout antibodies could be detected in serum from individual trout surviving VHSV exposure, immunised by injection with purified VHSV or DNA-immunised with its pG gene whereas it was not detected in non-infected and non-immunised trout. The trout serum antibodies which reacted more strongly by ELISA using solid-phase frg#11 (continuous or linear epitopes on the sequence of the pG) had the lowest VHSV-neutralising activity (epitopes which are pG conformation-dependent). Because antibodies recognising continuous as well as conformation-dependent epitopes of the pG seem to be involved in protective trout immunological responses to VHSV, the estimation of anti-frg#11 antibodies could help to the dissection of the complex trout antibody response to VHSV infections. In addition, these preliminary results suggest that the determination of anti-frg#11 antibodies might also be used to complement in vitro viral neutralising assays which seem to be restricted to pG conformation-dependent epitopes.

Animals↗

Enhanced detection of viral hemorrhagic septicemia virus (a salmonid rhabdovirus) by pretreatment of the virus with a combinatorial library-selected peptide.

A 17-mer peptide (SAAEASAKATAEATAKG, p5) was selected by screening a combinatorial library for its ability to enhance in vitro the infectivity of viral hemorrhagic septicemia virus (VHSV), a salmonid rhabdovirus. Preincubation of VHSV samples with p5 at micromolar concentrations led to up to 5-fold increase of viral titers compared to untreated samples, as measured by a 1-day post-infection immunochemical focus assay. Treatment with p5 also increased VHSV titers when using the more traditional plaque and end-point dilution assays. Preincubation of p5 with infectious hematopoietic necrosis virus (another rhabdovirus of salmonids), but not with infectious pancreatic necrosis virus (birnavirus) also led to a similar increase in sensitivity. These results indicate that the addition of p5 may be used to improve the sensitivity of diagnostic tests for salmonid rhabdoviruses.

Amino Acid Sequence↗

Abnormally increased semantic priming in children with symptomatic HIV-1 disease: evidence for impaired development of semantics?

Language deficits are a major characteristic of neurobehavioral dysfunction in pediatric HIV disease. An object decision task, which assessed reaction time facilitation following a semantic or identical prime in comparison to an unrelated prime, was used to investigate whether semantic processing abnormalities could be responsible, in part, for these deficits. Thirty children with vertically acquired HIV infection (M age 9.0 years; range 6-13) participated. Either a picture of the same object (repetition prime), a semantically related object (semantic prime), a semantically unrelated object, or a nonsense object preceded a target picture, which in 50% of the cases was a real object. Brain scans of children were rated and used together with neurobehavioral functioning to classify children as having HIV-related CNS abnormalities (n = 13) or not (n = 17). Increased semantic priming but not repetition priming was associated with a greater degree of cortical atrophy. Furthermore, CNS compromised children had significantly faster reaction times following a semantic prime compared to an unrelated prime than non-compromised patients. This facilitation following semantic priming for the CNS compromised patients (13.3%) almost equaled the facilitation following repetition priming (15.3%) while for the non-compromised patients facilitation following semantic priming (7.9%) was clearly smaller than following repetition priming (14.6%). These data suggest that HIV infection in children may result in a reduced neural network leading to impoverished semantic representations characterized by poor differentiation between closely related objects.

Acquired Immunodeficiency Syndrome↗

Kinetics and toxicity of direct reaction between ozone and 1,2-dihydrobenzene in dilute aqueous solution.

The presence of toxic aromatic organic compounds in industrial wastewater affects the efficiency of conventional biological treatment. The oxidizing power of ozone represents an interesting pretreatment to reduce toxicity and increase biodegradability. At low pH, ozone is known to attack electron-rich structures by direct electrophilic reactions which open aromatic rings, and generate smaller oxidized compounds. This paper reports experimental results on kinetic and toxicity aspects of ozone direct reactions with 1,2-dihydrobenzene. This toxic compound is frequently found in cellulose bleaching effluents. Although the reaction pathway is rather complex, 4-carbon compounds, such as maleic acid, are readily formed during the first stage of ozonation. These 4-carbon compounds are further oxidized to form smaller molecules (mostly 2-carbon, such as oxalic acid). The apparent kinetics of 1,2-dihydrobenzene follows a second order law, with a rate constant around 0.36 (dm3 mmol-1s-1), at pH 2 and 20 degrees C. Results show that the BOD:COD ratio increase five-fold as ozonation progresses. Furthermore, the mutagenicity of 1,2-dihydrobenzene totally disappears as the aromatic compound is destroyed by ozonation.

Benzene↗

Erythropoietin mediates terminal granulocytic differentiation of committed myeloid cells with ectopic erythropoietin receptor expression.

OBJECTIVES: The precise role of hematopoietic cytokine/cytokine receptor interactions in lineage-restricted hematopoietic differentiation giving rise to mature blood cells of diverse function is incompletely defined. To study lineage-specific effects of cytokines during terminal hematopoietic differentiation, we examined the ability of erythropoietin (Epo) to mediate terminal granulocytic differentiation and induction of myeloid gene expression in committed myeloid cells, engineered to ectopically express Epo receptor (EpoR). METHODS: A cell culture model for granulocyte-macrophage colony stimulating factor (GM-CSF)-mediated granulocytic differentiation was used. EpoR was introduced by retrovirus-mediated gene transfer into multipotential, hematopoietic murine cell line EML, from which GM-CSF-responsive, promyelocytic EPRO cells were generated. In EPRO cells ectopically expressing EpoR, we examined the ability of Epo to mediate granulocytic differentiation and determined whether Epo-mediated neutrophil differentiation is associated with a pattern of myeloid gene expression comparable to that induced by GM-CSF. RESULTS: Studies of EpoR function in myeloid EPRO cells revealed that Epo/EpoR interaction can mediate terminal granulocytic differentiation of committed myeloid cells. In EPRO cells expressing EpoR, Epo-mediated neutrophil differentiation was associated with surface CD11b/CD18 (Mac-1) expression and induction of mRNA expression of specific myeloid genes including lactoferrin, gelatinase and C/EBPepsilon, in a manner similar to GM-CSF-mediated differentiation. CONCLUSIONS: These results indicate that Epo can deliver differentiative signals along a non-erythroid lineage, providing evidence for interchangeable cytokine receptor signals that mediate terminal differentiation of committed myeloid cells.

Animals↗