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Biomedical subjects

V Alvarez

Publications and source records attributed to V Alvarez.

At least 91 records · Page 5Linked to original sources
PubMed1996

Relationship between birth weight and awake blood pressure in children and adolescents in absence of intrauterine growth retardation.

This study was designed to examine the relationship between birth weight (BW) and ambulatory blood pressure in children and adolescents, born at term in absence of intrauterine growth retardation. Twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed on 332 children (150 boys), aged from 6 to 16 years. Subjects were stratified by BW tertiles and age. ABPM was performed using SpaceLabs 90207 monitor during a regular school day. Blood pressure (BP) was measured every 20 min from 06:00 to 24:00, and thereafter every 30 min. Means of systolic BP (SBP) and diastolic BP (DBP) during 24 h, daytime (08:00 to 22:00), and nighttime (24:00 to 06:00) were calculated. Systolic and diastolic load was estimated as the percentage of measurements above the age- and sex-specific 95th percentile during the 24 h. BW was inversely related to daytime (SBP (P = .04) and SBP load (P = .04) when controlled for sex, current height, ponderal index (weight/height3), and age. The predictive values of daytime SBP throughout the pediatric age group in the two extreme tertiles of BW (lowest, 2.500 to 3.200 kg; and highest, 3.501 to 4.820 kg) were obtained from regression equations including SBP during activity period or SBP load and age. Children who had lower BW tended to have higher daytime SBP or SBP load at any age although this difference was not statistically significant. These differences became more evident as the subjects got older. BW is a determinant of daytime SBP even in the absence of intrauterine growth retardation. The influence of BW seems to increase with age.

Adolescent↗
PubMed1996

HLA-B27 structure, function, and disease association.

The polymorphism of HLA-B27 alleles is located in the peptide-anchoring motif. In recent years, fundamental insights have been made into the molecular aspects of HLA-B27-restricted presentation. Subtle differences in peptide binding fine specificity are especially interesting for closely related HLA-B27 alleles that have differential association with ankylosing spondylitis. Bacterial infection has been suggested to play a role in the pathogenesis of HLA-B27-associated disease. Remarkable progress has been made in identifying peptides derived from bacteria that can be presented by HLA-B27. Despite the mechanisms proposed to explain B27-associated diseases, there are no clear correlations between peptide sequence, differential binding to B27 subtypes, and recognition by peptide-specific T cell receptors. Furthermore, new transgenic models have now been developed that we hope will allow a clearer view of the function of B27 and the mechanisms involved in the pathogenesis of spondyloarthropathies.

HLA-B27 Antigen↗
PubMed1996

Trypsin activation pathway of rotavirus infectivity.

The infectivity of rotaviruses is increased by and most probably is dependent on trypsin treatment of the virus. This proteolytic treatment specifically cleaves VP4, the protein that forms the spikes on the surface of the virions, to polypeptides VP5 and VP8. This cleavage has been reported to occur in rotavirus SA114fM at two conserved, closely spaced arginine residues located at VP4 amino acids 241 and 247. In this work, we have characterized the VP4 cleavage products of rotavirus SA114S generated by in vitro treatment of the virus with increasing concentrations of trypsin and with proteases AspN and alpha-chymotrypsin. The VP8 and VP5 polypeptides were analyzed by gel electrophoresis and by Western blotting (immunoblotting) with antibodies raised to synthetic peptides that mimic the terminal regions of VP4 generated by the trypsin cleavage. It was shown that in addition to arginine residues 241 and 247, VP4 is cleaved at arginine residue 231. These three sites were found to have different susceptibilities to trypsin, Arg-241 > Arg-231 > Arg-247, with the enhancement of infectivity correlating with cleavage at Arg-247 rather than at Arg-231 or Arg-241. Proteases AspN and alpha-chymotrypsin cleaved VP4 at Asp-242 and Tyr-246, respectively, with no significant enhancement of infectivity, although this enhancement could be achieved by further treatment of the virus with trypsin. The VP4 end products of trypsin treatment were a homogeneous VP8 polypeptide comprising VP4 amino acids 1 to 231 and a heterogeneous VP5, which is formed by two polypeptide species (present at a ratio of approximately 1:5) as a result of cleavage at either Arg-241 or Arg-247. A pathway for the trypsin activation of rotavirus infectivity is proposed.

Amino Acid Sequence↗
PubMed1996

Diurnal blood pressure curve in children and adolescents.

OBJECTIVE: To investigate the diurnal blood pressure curve in healthy normotensive children. Thirty-one children were re-examined after a median interval of 123 days in order to study the reproducibility of the diurnal profile. SUBJECTS: Twenty-four-hour ambulatory blood pressure monitoring and conventional blood pressure readings were obtained in 228 normotensive children, whose ages ranged from 6 to 16 years and of whom 116 were boys and 112 girls. RESULTS: The conventional blood pressure averaged 99+/-11/57+/-9 mmHg in boys and 98+/-12/56+/-9 mmHg in girls (means+/-SD); the corresponding 24 h pressures were 111+/-7/66+/-5 mmHg and 109+/-7/65+/-5 mmHg, respectively. Of the children, 83% had a significant diurnal blood pressure rhythm for systolic pressure and 89% for diastolic pressure. The nocturnal blood pressure fall was normally distributed, averaging 12.0+/-6.3 mmHg systolic and 14.2+/-5.9 mmHg diastolic. There was no evidence for a bimodal distribution. The amplitude of the diurnal blood pressure curve, determined by the Fourier approach, was positively skewed with a mean of 12.5+/-4.2 mmHg for systolic and 14.0+/-4.1 mmHg for diastolic blood pressure. The daily blood pressure maximum occurred at 1344+/-4 h 46 min for systolic and 1321+/-4 h 22 min for diastolic blood pressure. For systolic blood pressure the cumulative sum (cusum)-derived circadian alteration magnitude was 1.7+/-6.2 mmHg higher in boys than in girls, whereas the cusum plot height was also 7.3+/-27.0 mmHg x h higher in male subjects. The repeatability coefficient (2SD of the difference between paired recordings, expressed as a percentage of nearly maximal variation) was 80% for the conventional systolic pressure and 40% for the conventional diastolic blood pressure. The repeatability coefficients for the ambulatory blood pressure levels varied from 32 to 45% and for the parameters describing the diurnal blood pressure profile from 42 to 78%. CONCLUSION: A significant diurnal blood pressure rhythm is observed in most normotensive children and adolescents. There is no evidence for a bimodal distribution of the nocturnal blood pressure fall. The reproducibility of the parameters of the diurnal blood pressure curve tended to be less than that of the ambulatory blood pressure level. Thus, one 24 h recording is probably insufficient to characterize a child's diurnal blood pressure profile fully.

Adolescent↗
PubMed1995

Characterization of the mannose 6-phosphate-dependent pathway of lysosomal enzyme routing in an invertebrate.

The mannose 6-phosphate (Man6P)-dependent pathway for routing lysosomal enzymes was characterized in the hepatopancreas of the estuary crab Chasmagnatus granulata: (a) an acid alpha-L-fucosidase was purified to homogeneity from the above-mentioned organ and was shown to contain mannose-linked phosphate residues; (b) high-mannose-type oligosaccharides isolated from a protein fraction enriched in acid hydrolases were found to contain acid-labile N-acetylglucosamine (GlcNAc) residues; (c) a membrane-bound UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase was detected that phosphorylated the estuary-crab alpha-L-fucosidase and bovine uteroferrin but not bovine pancreas ribonuclease B; (d) a GlcNAc-1-phosphodiester alpha-N-acetylglucosaminidase that released GlcNAc units from GlcNAc alpha 1-P6Man alpha 1-methyl was detected in microsomal membranes of the hepatopancreas; (e) two detergent-solubilized microsomal proteins having molecular masses of 205 and 215 kDa that were retained by a Man6P-rich mannan-Sepharose column, from where they were eluted with Man6P but not with glucose 6-phosphate, were recognized by antisera raised against bovine large (215 kDa) and small (46 kDa) Man6P receptors. This is the first description of all the components of the Man6P-dependent mechanism for routing lysosomal enzymes in an invertebrate.

Acetylglucosamine↗
PubMed1995

Genetic detection of the silent allele (*Q0) in hereditary deficiencies of the human complement C6, C7, and C9 components.

DNA polymorphisms (RFLPs) of the human complement component C6, C7, and C9 genes were studied in three C7-deficient (C7D) families, one C6-deficient (C6D) family, and one C9-deficient (C9D) family. The 3 loci are closely linked on human chromosome 5. The haplotypes carrying the "silent" allele (C7*Q0, C6*Q0, and C9*Q0) were defined in each family, allowing for the detection of carriers among asymptomatic relatives. This paper describes familial studies on a type of hereditary trait, characterized by recurrent Neisseria infections in individuals homozygous for "silent" alleles at the C6, C7, or C9 loci.

Alleles↗
PubMed1995

[Ambulatory arterial blood pressure in normotensive children].

BACKGROUND: The aim of the present study was to obtain out patient blood pressure values in normotensive children based on age, height, and sex in order to determine reference values. METHODS: Out patient blood pressure monitorization was performed in 248 healthy normotensive children (129 males and 119 females, ages 6 to 16 years) (casual blood pressure < P95 specific for age and sex) over 24 hours by the Spacelabs 90207 oscilometric monitor on a normal schoolday. An appropriately sized armband was chosen for each case with the readings being programmed every 20 minutes between 6:00 a.m. and midnight and every 30 minutes for the remaining readings. The means of 24 hour blood pressure (all the readings obtained), day period (8 to 22 hours) and night period (midnight to 6:00 a.m.) and the circadian variability (difference and the ratio between the mean values of day and night) were calculated. The children were divided into subgroups according to sex, age (6-9, 10-12 and 13-16 years) and height (1.09-1.37; 1.38-1.51, and 1.52-1.75 meters). Monitorizations with a percentage of erroneous readings over 30% were excluded from the study. RESULTS: Only 7 children were excluded due to a high percentage of erroneous readings. The mean of the valid readings made in the remaining 241 cases was 62 +/- 7. A significant increase was observed in the values of out patients systolic blood pressure with age and height. The same was not seen in diastolic blood pressure. Nocturnal blood pressures were lower to the diurnal pressures (11% systolic, 22% diastolic). P95 was considered as the upper limit of normality for the means of each of the periods of systolic and diastolic blood pressure in each subgroup of sex, age and height. CONCLUSIONS: The blood pressure values obtained from a population of normotensive children may be useful to understand the behaviour of out patient blood pressure in children and establish the limit for defining high blood pressure.

Adolescent↗
PubMed1995

Monocyte activation: rapid induction of alpha 1/beta 1 (VLA-1) integrin expression by lipopolysaccharide and interferon-gamma.

Monocytes play a key role in inflammation, tissue injury and remodelling and wound healing, and most monocyte effector functions are dependent on adhesive interactions. We have analyzed the changes in the pattern of beta 1 integrin expression that take place during monocyte activation and demonstrated that lipopolysaccharide (LPS) and interferon (IFN)-gamma specifically induce the expression of the alpha 1/beta 1 integrin, which was detectable on the monocyte membrane as early as 12 h after monocyte activation. The up-regulated alpha 1/beta 1 expression was not dependent on monocyte adherence to solid surfaces, and Northern blot analysis revealed that LPS and IFN-gamma induce the alpha 1 mRNA de novo. Monocyte deactivating cytokines such as interleukin (IL)-4 or IL-10, could only minimally inhibit the LPS- or IFN-gamma mediated up-regulation of alpha 1/beta 1, suggesting that cytokine release subsequent to monocyte activation does not play a major role in the integrin induction. Interestingly, the LPS-induced expression of alpha 1/beta 1 was found to be dependent on the redox state of the cell, since it was inhibited by antioxidants which also altered the morphological changes that take place during monocyte culture in vitro. The rapid induction of alpha 1 in LPS-activated monocytes suggests that alpha 1/beta 1 might be involved not only in monocyte/extracellular matrix interactions during inflammatory reactions, but also in contributing to further monocyte activation and cytokine production during septic shock syndrome.

Cell Adhesion↗
PubMed1995

Characterization of B27 haplotypes by oligotyping and genomic sequencing in the Mexican Mestizo population with ankylosing spondylitis: juvenile and adult onset.

The aim of this study was to investigate the contribution of the different B27 subtypes in the Mexican Mestizo population with juvenile and adult AS. No differences in the distribution of B27 subtypes were found between both populations, B*2705 being the predominant subtype followed by B*2702. Transracial gene mapping was performed in order to find out the origin of the B27 alleles of the Mexican Mestizos. A PCR with SSOPs was used to analyze the polymorphism in exons 2 and 3 of HLA-B27 and HLA-C related alleles. This population shares with the Spanish Caucasians B*2705 and B*2702, which are absent in Central and South American Indians. AS and healthy Mexican mestizo donors were analyzed to ascertain B27/Cw haplotypes. The B27/Cw linkage arrangements seen in mestizos are similar to those reported for Caucasian Spaniards with three different haplotypes positively associated with AS in both populations, B*2705/Cw*0102, B*2705/Cw*02022, and B*2702/Cw*02022, suggesting that B27 in Mexicans may be due to a recent Caucasoid admixture with the Spanish genes. Finally, a strategy for sequence analysis of exons 2 and 3 from genomic DNA of HLA-B27 alleles was developed. A novel HLA-B27-like allele typed serologically as B27 was identified and sequenced by this method in a healthy Mexican mestizo, corresponding to the B*7301 variant found with low frequency in different populations. Analysis of the association of B*7301 to AS would require an extensive study in different populations and could provide insights into the molecular structure of the alleles involved in the disease.

Adolescent↗
PubMed1994

Prevention of mercuric chloride-induced nephritis in the brown Norway rat by treatment with antibodies against the alpha 4 integrin.

HgCl2 induces the synthesis of anti-GBM Abs with the development of glomerular and interstitial nephritis, as well as proteinuria, in the Brown Norway rat. The development of this autoimmune disease is a consequence of the appearance of an autoreactive T cell subset-inducing activation of B cells. The administration to mercury-treated rats of the mouse anti-human VLA alpha 4 HP2/1 mAb, which cross-reacts with the rat homologue integrin, completely abrogated the interstitial cell infiltrates. As demonstrated by peripheral blood analysis, this effect is not a result of the depletion of circulating leukocytes or leukocyte subsets. Interestingly, the administration of Abs specific for the alpha 4 integrin also highly reduced anti-GBM Ab synthesis, thus preventing detectable glomerular deposits and proteinuria. Our results confirm that in vivo alpha 4 functions in adhesive interaction of circulating leukocytes and vascular endothelium, and is centrally important in the extravasation and migration of T lymphocytes to sites of tissue injury. We also found a complete absence of interstitial cell infiltrates, together with a positive glomerular IgG lineal deposition pattern, when anti-GBM Abs were passively transferred to rats pretreated with anti-alpha 4 mAb, thus indicating an independent role of alpha 4 integrin in both extravasation of immune cells and production of autoantibodies. Furthermore, these in vivo findings provide preliminary evidence for the participation of the VLA-4 integrin in mediating the intercellular interaction of leukocytes regulating the production of Abs, most likely through the existence of additional yet unknown ligand(s).

Animals↗
PubMed1994

Regulation of ICAM-3 (CD50) membrane expression on human neutrophils through a proteolytic shedding mechanism.

The regulation of the cell surface expression of ICAM-3 (CD50) was investigated in human neutrophils. Immunofluorescence flow cytometry analysis revealed a remarkable and very rapid down-regulation of the ICAM-3 cell surface expression upon neutrophil activation with stimulating agents such as phorbol myristate acetate (PMA) or calcium ionophore. A similar low expression of ICAM-3 was observed on neutrophils from patients undergoing hemodialysis with cell-activating cellulosic membranes. Internalization assays with 125I-labeled anti-ICAM-3 monoclonal antibody (mAb) suggested that ICAM-3-down-regulation was due to antigen release from the cell surface towards the outer milieu, rather than to antigen internalization. Immunoprecipitation studies confirmed this down-regulatory effect, and revealed the presence of ICAM-3 in cell-free supernatants from activated neutrophils. Furthermore, the presence of a soluble form of ICAM-3 with a range of concentrations of 0-296 ng/ml in the plasma from healthy human volunteers was detected by using a two-site mAb radioimmunoassay. A proteolytic mechanism likely accounts for this process since protease inhibitors virtually abrogated the PMA-induced down-regulation of ICAM-3. Functional studies showed that anti-ICAM-3 mAb were able to trigger homotypic neutrophil aggregation both before and after ICAM-3 down-regulation, indicating that the fraction of ICAM-3 molecules remaining on the neutrophil surface upon activation are still capable of sustaining cell adhesion. In contrast, the loss of L-selectin (CD62L) on activated neutrophils was almost complete, thus leading to an impairment of L-selectin-mediated neutrophil-endothelial cell adhesion. These results indicate that ICAM-3 is released to the medium upon neutrophil stimulation and that both ICAM-3 and L-selectin have a role in the neutrophil adhesive phenomena.

Antigens, CD↗
PubMed1994

A physical map of two clusters containing the genes for six proinflammatory receptors.

The genes encoding for six receptors involved in the proinflammatory response lie on different chromosomes. Two receptors for N-formylpeptides (FPR1, FPR2), one homologue of these (FPRL2), and the receptor for complement fragment C5a (C5aR) are encoded by four genes mapped to human chromosome 19. The genes encoding two receptors for Interleukin-8 (IL8RA, IL8RB) have been located on human chromosome 2. In this report we describe the physical linkage between these genes in two different clusters. DNA fragments obtained by digestion with several restriction enzymes were separated by pulsed field gel electrophoresis. Nylon filters were hybridized with probes corresponding to the complete translated sequences of these genes. These probes were obtained from a human neutrophil cDNA-library. The four genes on chromosome 19 are contained in a 200 kilobase (kb) fragment. Both Interleukin-8 receptors are on a 150 kb fragment. The complete translated sequences for these genes were amplified from genomic DNA, indicating that they are contained in a single exon.

Base Sequence↗
PubMed1994

Molecular analysis of HLA-B27 haplotypes in Caucasoids. Frequencies of B27-Cw in Jewish and Spanish populations.

PCR in combination with SSO probes was used to analyze the polymorphism in exons 2 and 3 of HLA-B27 subtypes and HLA-C-related alleles in two genetically distant Caucasian groups: Spanish and Jewish populations. AS patients and healthy B27 donors from both populations were analyzed in order to ascertain B27-Cw haplotypes. Three different ancestral haplotypes were found to be represented in both populations: B*2705/Cw*0102, B*2705/Cw*02022, and B*2702/Cw*02022. The B*2705 (92.5%) was the most frequent allele found in the Spanish population, carried by B*2705/Cw*0102 (60.9%) and B2705/Cw*02022 (30.4%) haplotypes. In contrast, B*2702 (59.4%) was the most prevalent allele found in the Jewish population and was carried by the B*2702/Cw*02022 (63.3%) haplotype. No different allelic and haplotypic distributions were among healthy and AS patients in either Spanish or Jewish populations. The differences found in the distribution of B27 haplotypes among Spanish and Jewish Caucasian populations are consistent with the genetic distance of these ethnic groups. When the Jewish population was subdivided into Ashkenazi (A) and non-Ashkenazi (NA) groups, no significant differences were observed in the distribution of B*2702/Cw*02022 haplotype. Minor differences were observed in the underrepresented B*2705 haplotypes. The present results reflect the ancestral affinities of A and NA Jewish populations. A possible HLA-B27 evolutive pathway in Caucasians is proposed according to the data available for the B27/Cw ancestral haplotypes in Spanish and Jewish groups.

Base Sequence↗
PubMed1994

Biological variation in urine samples used for analyte measurements.

To determine the influence of biological variation on the reliability of data from different types of urine specimens, we measured nine analytes in first-morning, randomly collected, and 24-h samples of urine from 53 healthy individuals (14 men and 39 women). The urines were collected once a week for 10 weeks. The data obtained were used as a basis for specimen collection and to gain insight into the influence of urine quantities in the diagnosis, screening, and monitoring of patients. We found that 24-h urine expressed in output rather than concentration units is the most reliable specimen for diagnosis and monitoring for most of the analytes studied. On the basis of the ratio between estimated within- and between-subject variation, the tests with greatest medical usefulness for diagnosis and screening of specific pathologies are those measuring protein and sodium. Moreover, the results indicate that urine creatinine may be a poor test for diagnosis, monitoring, and screening.

Adult↗
PubMed1994

Ambulatory blood pressure monitoring in normotensive children.

OBJECTIVE: To assess reference values of ambulatory blood pressure in normotensive children. SUBJECTS AND DESIGN: Twenty-four-hour non-invasive ambulatory blood pressure monitoring (ABPM) was carried out in 241 healthy normotensive children aged from 6 to 16 years (126 boys, mean +/- SD age 11.2 +/- 2.7 years; 115 girls, mean +/- SD age 10.9 +/- 2.9 years). The subjects were subdivided into three age-sex groups: 6-9, 10-12 and 13-16 years. SETTING: Primary care. MAIN OUTCOME MEASURES: ABPM was performed using an oscillometric device (SpaceLabs model 90207) and appropriate cuff size during a regular school day. Blood pressure was measured every 20 min from 0600 to 2400 h, and thereafter every 30 min. At each monitoring session the following parameters were calculated for both systolic (SBP) and diastolic blood pressure (DBP): means and centiles for 24-h, daytime (0800-2200 h) and night-time (2400-0600 h); circadian variability, estimated as the blood pressure fall between the day and the night periods and the day: night ratio; and load, as the percentage of measurements above the age- and sex-specific 95th centile (P95). RESULTS: The upper limits of 'normality' for the mean of 24-h SBP and DBP estimated as the P95 in each age subgroup were 121/71 and 119/71 mmHg, 123/78 and 120/74 mmHg, and 124/78 and 125/75 mmHg, for boys and girls, respectively. A progressive increase in SBP with age was observed in both sexes, in contrast, DBP was similar throughout the age range. A nocturnal blood pressure fall of approximately 11 mmHg was observed for both SBP and DBP in all subgroups. The day:night ratio was 1.12 and 1.22 for SBP and DBP, respectively. The upper limit of blood pressure load, estimated as the P95 in all children, was 39% for SBP and 26% for DBP. A significant positive correlation was observed between casual blood pressure and 24-h ambulatory blood pressure (SBP: r = 0.61, P < 0.0001; DBP: r = 0.31, P < 0.0001). In general, mean ambulatory blood pressure, during the 24-h or the daytime period, was higher than casual blood pressure for both SBP and DBP. CONCLUSION: ABPM is feasible in children, and the values obtained are useful as a departure point in establishing reference values.

Adolescent↗