Polymorphisms of the angiotensinogen gene and the outcome of microalbuminuria in essential hypertension: a 3-year follow-up study.

Background: The objective of this study was to analyse the relationship of polymorphisms of the angiotensinogen (AGT) gene with the changes in microalbuminuria during 3 years of antihypertensive treatment in a group of young adults with essential hypertension.

Methods: Essential hypertensives, less than 50 years old, never previously treated with antihypertensive drugs and in the absence of diabetes mellitus were included. After the initial evaluation, patients were treated using only nonpharmacological measures (n=23), only beta-blockers (n=26), only angiotensin-converting enzyme inhibitors (ACEi) (n=57) or a combination of treatments (n=25).

Levels of mucin gene expression in normal human conjunctival epithelium in vivo.

Purpose: Conjunctival impression cytology (CIC) samples were used to determine the mean and normal range of mRNA levels of human MUC1, MUC2, MUC4, MUC5AC, and MUC7 mucin genes.

Methods: Real time PCR was performed to determine normal mRNA levels in CIC samples of 24 male and 19 female healthy donors. Correlation coefficients between gene expression levels were obtained.

Recent transmission of tuberculosis in Madrid: application of capture-recapture analysis to conventional and molecular epidemiology.

Background: Population-based studies using a combination of molecular techniques and conventional epidemiological methods have been used to study the dynamics of tuberculosis (TB) transmission but the relative utility of each technique has not yet been established.

Methods: A prospective population-based molecular and epidemiological study of patients diagnosed with TB was conducted in three urban districts of Madrid (Spain) during 1997-1999. Analysis was performed using the capture-recapture method including covariates in which conventional epidemiological data and the information on clustered cases obtained by DNA fingerprinting were regarded as independent and complementary procedures.

Mutational analysis of BRCA1 and BRCA2 in Mediterranean Spanish women with early-onset breast cancer: identification of three novel pathogenic mutations.

In Spain, the contribution of BRCA mutations to the population incidence of early-onset breast cancer was unknown. We carried out a mutational analysis of the BRCA1 and BRCA2 genes in 124 Spanish women diagnosed with breast cancer before the age 41 and who were not selected for a family history of this disease. The genetic study was performed by PCR-SSCP analysis and DNA sequencing.

Influence of LDL receptor gene mutations and the R3500Q mutation of the apoB gene on lipoprotein phenotype of familial hypercholesterolemic patients from a South European population.

Few data are available on genotype-phenotype interactions among familial hypercholesterolemia (FH) patients in South European populations and there are no data about the influence of R3500Q mutation on lipoprotein phenotype compared to low-density lipoprotein receptor (LDLR) mutations. The objective of the study is to analyze the influence of mutations in the LDLR and apolipoprotein B (apoB) genes on lipoprotein phenotype among subjects clinically diagnosed of FH living in East Spain. In all, 113 FH index patients and 100 affected relatives were studied.

Human epithelium from conjunctival impression cytology expresses MUC7 mucin gene.

Purpose: To prove that noninvasive methods of obtaining conjunctival tissue, such as conjunctival impression cytology (CIC), could be valid alternatives that are simpler, faster, and more convenient for patients than biopsy to analyze mRNA levels of mucin genes.

Methods: Using the semiquantitative reverse-transcriptase polymerase chain reaction, we studied the presence of the mucin genes described on the ocular surface thus far and attempted to detect the presence of MUC7 in CIC samples from 10 healthy donors.

Results: Conjunctival cells recovered by CIC expressed all the genes studied.

Neutrophils do not contribute to local tissue damage, but play a key role in skeletal muscle regeneration, in mice injected with Bothrops asper snake venom.

Local tissue damage induced by crotaline snake venoms includes edema, myonecrosis, hemorrhage, and an inflammatory response associated with a prominent cellular infiltrate. The role of neutrophils in the local tissue damage induced by Bothrops asper snake venom and by myotoxin I, a phospholipase A2 isolated from this venom, was investigated. Male Swiss mice were pretreated with either an antimouse granulocyte rat monoclonal immunoglobulin G (IgG) antibody or with isotype-matched control antibody.

[Normal human conjunctival epithelium expresses MUC13, MUC15, MUC16 and MUC17 mucin genes].

Purpose: The ocular surface epithelia express at least five mucin genes of the total of 17 human mucin genes that have been identified so far. This study was designed to determine the expression profile of mucin genes in conjunctival impression cytology (CIC) samples from healthy subjects.

Methods: Two polyethersulfone filters were applied to the superior conjunctiva of both eyes from eight healthy donors.

Intramuscular administration of antivenoms in experimental envenomation by Bothrops asper: comparison between Fab and IgG.

The efficacy of intramuscular (im) administration of sheep Fab and IgG antivenoms was assessed in a mouse experimental model of envenomation by Bothrops asper, in order to test if the more rapid absorption of Fab improves neutralization. Both antivenoms were adjusted to have a similar neutralizing potency in assays involving preincubation of venom and antivenom. Neither antivenom was effective in neutralizing lethality, nor in prolonging the time of death, in mice injected with either 3, 2 or 1.

Meningitis due to mixed infection with penicillin-resistant and penicillin-susceptible strains of Streptococcus pneumoniae.

Streptococcus pneumoniae is the major cause of bacterial meningitis. We report a case of meningitis due to a mixed infection with two distinct strains of S. pneumoniae: one penicillin-resistant strain of serotype 9V and one penicillin-susceptible strain of serotype 7.

Body weight changes and the A-6G polymorphism of the angiotensinogen gene.

Background: The objective of the study was to analyze the relationship of polymorphisms of the angiotensinogen gene with changes in body weight during 3 y of antihypertensive treatment, in a group of young adults with essential hypertension.

Methods: Essential hypertensives, less than 50 y old, never previously treated with antihypertensive drugs and in the absence of diabetes mellitus were included. After the initial evaluation, patients were treated using only non-pharmacological measures (n=29), beta-blockers (n=40) or angiotensin-converting enzyme inhibitors (n=66).

[Influence of plasma lipids, APOE genotype and type of LDL receptor gene mutations on myocardial infarction in subjects with familial hypercholesterolemia].

Background: Our goal was to analyze the relationship of lipids and lipoproteins, APOE genotype and mutations of the LDL receptor gene with the prevalence of myocardial infarction (MI) in patients with familial hypercholesterolemia (FH) from a Southern European FH population.

Patients And Method: We studied 108 heterozygous FH subjects aged > 35 years (41 males). It was a cross-sectional study comparing individuals with FH and MI with individuals with FH without MI.

[Recent transmission of tuberculosis in an area with low incidence: epidemiological and molecular study].

Background: Few reports have analysed the transmission of tuberculosis in rural areas with a low incidence of disease.

Patients And Method: A population-based molecular epidemiological study of patients with tuberculosis, diagnosed by culture, was conducted in Segovia (Spain) between 1995 and 1999. Clinical, demographic and epidemiological data were reviewed.

Value of autopsy in nonimmune hydrops fetalis: series of 51 stillborn fetuses.

Nonimmune hydrops fetalis (NIHF) is used to describe fetuses and newborns with generalized edema and cavity effusions. It is helpful to alert physicians about the presence of anemia, heart failure, and/or hypoproteinemia, but this diagnosis is frequently overlooked. We reviewed the autopsy files from 1990 to 2000, selected all cases with NIHF including clinical information (with maternal laboratory tests and ultrasound), and classified patients by etiology.

[Genetic polymorphisms of the renin-angiotensin system and essential hypertension].

Background: The renin-angiotensin system (RAS) is known to regulate the blood pressure (BP). Several RAS polymorphisms have been associated with essential hypertension (EH), but there is uncertainty about this association. We examined whether the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene, and the M235T polymorphism of the angiotensinogen (AGT) gene were associated with EH in a sample of Spanish hipertensive patients.

Double dimer peptide constructs are immunogenic and protective against Plasmodium falciparum in the experimental Aotus monkey model.

Multiple antigen peptide constructs (MAPs) have been used to obtain defined multimeric peptide molecules useful in the development of possible synthetic malaria vaccines. In this context, a method was developed, named double dimer constructs (DDCs), involving the direct synthesis of a dimeric peptide with a C-terminal cysteine. A tetrameric molecule was then obtained by oxidation of sulfhydryl groups.

New real-time PCR able to detect in a single tube multiple rifampin resistance mutations and high-level isoniazid resistance mutations in Mycobacterium tuberculosis.

The emergence of resistance to antituberculosis drugs is a relevant matter worldwide, but the retrieval of antibiograms for Mycobacterium tuberculosis is severely delayed when phenotypic methods are used. Genotypic methods allow earlier detection of resistance, although conventional approaches are cumbersome or lack sensitivity or specificity. We aimed to design a new real-time PCR method to detect rifampin (RIF)- and isoniazid (INH)-resistant M.

[Renin-angiotensin system genetic polymorphisms and essential hypertension in the Spanish population].

Background: The goal of this study was to analyse the association between essential hypertension and the main genetic polymorphisms at the renin-angiotensin system in the Spanish population.

Patients And Method: Case-control study including 185 essential hypertensive subjects(age [SD] 39.6 [7.

Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis.

Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have been carried out on Spanish FH patients up to now. To gain information on this issue, we have analysed a group of 113 unrelated Spanish FH patients from an eastern area of Spain (Valencian Community). We have screened the LDLR gene by Southern blot and PCR-SSCP analysis to detect large rearrangements and small mutations, respectively.

Synthesis, isolation and characterization of Plasmodium falciparum antigenic tetrabranched peptide dendrimers obtained by thiazolidine linkages.

Different chemical alternatives were evaluated for obtaining immunogenic polypeptidic macromolecules which could then be used as vaccines. These were based on the ligation reaction between an unprotected immunogenic peptide and an unprotected multifunctional core peptide; polyantigens, designated dendrimers because their form resembles that of dendritic cells, were thus obtained. The antigen-core ligation alternatives, studied by indirect synthesis, were the formation of oxime, hydrazone and thiazolidine linkages, making use of the reaction between a weak base (acting as nucleophile) and an alkyl aldehyde.

Genetic diagnosis of familial hypercholesterolemia in a South European outbreed population: influence of low-density lipoprotein (LDL) receptor gene mutations on treatment response to simvastatin in total, LDL, and high-density lipoprotein cholesterol.

The aims of this study were to examine the presence of mutations in the low-density lipoprotein receptor gene among subjects clinically diagnosed with familial hypercholesterolemia and to analyze whether the molecular diagnosis helps to predict the response to simvastatin treatment in our familial hypercholesterolemia population. Fifty-five probands and 128 related subjects with familial hypercholesterolemia were studied. Genetic diagnosis was carried out following a three-step protocol based on Southern blot and PCR-single strand conformational polymorphism analysis.

The influence of HIV infection and imprisonment on dissemination of Mycobacterium tuberculosis in a large Spanish city.

Setting: Culture-positive cases of tuberculosis (TB) from the urban population of southern Madrid and from all the prisons located throughout the city.

Objective: To determine the frequency with which common strains of Mycobacterium tuberculosis cause disease among patients from both the urban and prison populations of a large Spanish city.

Design: Restriction fragment length polymorphism analysis was performed on culture-positive cases of TB identified between 1 January 1997 and 31 December 1998.

Inhibition of local hemorrhage and dermonecrosis induced by Bothrops asper snake venom: effectiveness of early in situ administration of the peptidomimetic metalloproteinase inhibitor batimastat and the chelating agent CaNa2EDTA.

The effectiveness of the chelating agent CaNa2EDTA and the peptidomimetic matrix metalloproteinase inhibitor batimastat (BB-94) to inhibit local tissue damage induced by Bothrops asper snake venom was studied in mice. Both compounds totally inhibited proteolytic, hemorrhagic, and dermonecrotic effects, and partially reduced edema-forming activity, when incubated with venom prior to injection. Much lower concentrations of batimastat than of CaNa2EDTA were required to inhibit these effects.

Angiotensin II AT1 receptor gene polymorphism and microalbuminuria in essential hypertension.

The objective of this study was to analyze the relationship of polymorphisms of the angiotensin II AT1 receptor gene with microalbuminuria in a group of young adults with essential hypertension. Essential hypertensives, less than 50 years old, never previously treated with antihypertensive drugs, and in absence of diabetes mellitus were included. Office blood pressure (BP), 24-h ambulatory BP monitoring, urinary albumin excretion (UAE) measurements, and DNA analysis were performed.