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Biomedical subjects

G Gutiérrez

Publications and source records attributed to G Gutiérrez.

At least 19 recordsLinked to original sources

Comparative gene expression profile of mouse carotid body and adrenal medulla under physiological hypoxia.

The carotid body (CB) is an arterial chemoreceptor, bearing specialized type I cells that respond to hypoxia by closing specific K+ channels and releasing neurotransmitters to activate sensory axons. Despite having detailed information on the electrical and neurochemical changes triggered by hypoxia in CB, the knowledge of the molecular components involved in the signalling cascade of the hypoxic response is fragmentary. This study analyses the mouse CB transcriptional changes in response to low PO2 by hybridization to oligonucleotide microarrays. The transcripts were obtained from whole CBs after mice were exposed to either normoxia (21% O2), or physiological hypoxia (10% O2) for 24 h. The CB transcriptional profiles obtained under these environmental conditions were subtracted from the profile of control non-chemoreceptor adrenal medulla extracted from the same animals. Given the common developmental origin of these two organs, they share many properties but differ specifically in their response to O2. Our analysis revealed 751 probe sets regulated specifically in CB under hypoxia (388 up-regulated and 363 down-regulated). These results were corroborated by assessing the transcriptional changes of selected genes under physiological hypoxia with quantitative RT-PCR. Our microarray experiments revealed a number of CB-expressed genes (e.g. TH, ferritin and triosephosphate isomerase) that were known to change their expression under hypoxia. However, we also found novel genes that consistently changed their expression under physiological hypoxia. Among them, a group of ion channels show specific regulation in CB: the potassium channels Kir6.1 and Kcnn4 are up-regulated, while the modulatory subunit Kcnab1 is down-regulated by low PO2 levels.

Adrenal Medulla↗

Regulation of interleukin-6 fetoplacental levels could be involved in the protective effect of low-molecular weight heparin treatment on murine spontaneous abortion.

PROBLEM: CBA/J x DBA/2 abortion rate could be the consequence of a deficient local production of T helper (Th2) cytokines, which cause fetal wastage via fgl2 prothrombinase. Heparin reduces significantly the abortion rate in mice and recurrent spontaneous abortion (RSA) patients. We proposed to determine the effect of enoxaparin on the levels of local interleukin (IL)-6 during murine pregnancy. METHOD OF STUDY: Recombinant human IL-6 (rhIL-6) or enoxaparin were inoculated in CBA/J x DBA/2 pregnant mice on days 6.5-12.5. IL-6 levels in sera as well as in culture supernatants of day 9.5 fetoplacental units of CBA/J x BALB/c control mice or CBA/J x DBA/2 abortion combination were determined by enzyme-linked immunosorbent assay (ELISA) test. RESULTS: CBA/J x DBA/2 fetoplacental units secreted significantly lower levels of IL-6 with regard to CBA/J x BALB/c normal units. rhIL-6h and enoxaparin treatments decreased the resorption rate and regulated IL-6 fetoplacental levels. CONCLUSION: This study suggests that regulation of IL-6 fetoplacental levels could be involved in heparin-mediated anticoagulation protection against abortion.

Abortion, Spontaneous↗

Determinants of patient delay among tuberculosis cases in Spain.

BACKGROUND: Patient delay was investigated in a cohort of TB patients identified from May 1996 until April 1997 in 13 Autonomous Regions in Spain. The study covered almost 67% of the total Spanish population. METHODS: Data were collected from clinical records. Using unconditional logistic regression with two different cut-off points to define 'patient delay' (the median and 75th percentile), the association between patient delay and different factors was estimated. RESULTS: A total of 7,037 cases were included. Median and 75th percentile delays were 22 and 57 days respectively. Factors associated with patient delay greater than the median (p<0.05) were: non-respiratory symptoms of TB and age over 14 years, although the effect of age was not linear. Furthermore, an interaction was observed between intravenous drug user (IDU) and HIV status, in that, whereas patient delay was greater in IDUs than in non-IDUs among cases whose HIV status was either negative or unknown, among HIV-positive patients no such IDU-related differences were in evidence. Factors associated with extreme patient delay (greater than the 75th percentile) were essentially the same, but the above-described interaction disappeared, with IDU status showing no direct effect. In addition, likelihood of extreme patient delay increased in the case of alcoholism and female gender and decreased in the case of chronic renal failure, corticoid treatment, prison inmates and residents of old age homes. CONCLUSION: Although there is a universally enjoyed right to health care in Spain, some groups of TB patients could nevertheless be experiencing problems in seeking medical attention.

Adolescent↗

Comparative effects of L-tryptophan and 1-methyl-tryptophan on immunoregulation induced by sperm, human pre-implantation embryo and trophoblast supernatants.

PROBLEM: The hypothesis that indoleamine 2,3-dioxygenase (IDO) is necessary to regulate lymphocyte functions at the feto-maternal interface has been postulated, although a possible role of tryptophan (Trp) depletion in the T-cell tolerance during insemination as well as implantation has not been previously investigated. METHOD OF STUDY: Allogeneic phytohaemagglutinin stimulated lymphocytes were supplemented with pre-implantation embryo supernatant (PES), seminal plasma (SP), spermatozoa culture supernatant (SCS), spermatozoa, trophoblast cells, or placenta explant culture supernatants, and analyzed for expression of CD25, CD71, and CD69. Trp-degrading activity was assessed by addition of 1-methyl-Tryptophan or L-Trp. RESULTS: PES, SP, trophoblast, and explant supernatants reduced the expression of CD25 in CD3 lymphocytes. Inhibition of IDO as well as Trp supplementation prevented these effects. CONCLUSIONS: These data suggest that the expression of interleukin-2 (IL-2) receptor in maternal T lymphocytes is normally suppressed by Trp catabolism, and that either abnormal IDO levels or substances influencing IDO activity might lead to non-adequate immune responses on sperm, harm the conceptus or even initiate fetal rejection.

Adult↗

Lambda(0) polarization in 800-GeV/cpp --> p(f)(Lambda0K+).

We report results from a study of Lambda(0) polarization in the exclusive reaction pp --> p(f)(Lambda0K+) at 800-GeV/c. We observe a dependence of the polarization on the Lambda0K+ invariant mass with large (+71%) positive polarization at small mass (1.63-GeV/c(2)) and large (-43%) negative polarization at large mass (2.75-GeV/c(2)). This observation confirms the result of the CERN ISR R608 experiment and extends the range over which the effect is observed. The strong dependence of the polarization on the Lambda0K+ invariant mass suggests that the origin of the polarization is closely related to the production dynamics of the diffractively produced Lambda0K+ system.

Journal Article↗

Interleukin regulation of asymmetric antibody synthesized by isolated placental B cells.

PROBLEM: Protecting antibodies against trophoblast surface molecules were previously described. Here we analysed the synthesis of asymmetric IgG by placental B-lymphocytes. METHOD OF STUDY: B cells were isolated from human term placenta and cord blood, stimulated with anti-CD40 IgG and cocultured with transfected Fcgamma R-expressing mice Ltk-fibroblast. Interleukin-4, IL-6, IL-10, IL-11 and IL-13 were added to cultures for 14 days. Asymmetric IgG were assessed in culture supernatants by concanavalin A (Con A) fixation and enzyme-linked immunosorbent assay. RESULTS: When IL-6 was added to the cultures, the percentages of asymmetric IgG synthesized by placental B cells were: IL-6: 29 +/- 10; IL-6 + IL-10: 24 +/- 7; IL-4 + IL-10 + IL-6: 38 +/- 9. The last combination induced the highest increase in the asymmetric IgG synthesis as compared with control (19 +/- 10%, P < 0.05). Additionally, placental B cells synthesized more asymmetric IgG than umbilical cord blood B-lymphocytes (P = 0.0015). CONCLUSIONS: Isolated placental B-lymphocytes synthesized asymmetric IgG in response to Th2 interleukins, more notably IL-6 in combination with IL-4 and IL-10. The in vitro increase of protective asymmetric IgG synthesis in response to Th2-cytokines support the hypothesis that a local Th2-switch is beneficial for pregnancy outcome.

Animals↗

Tuberculosis in Spain: epidemiological pattern and clinical practice.

SETTING: Thirteen Autonomous Regions in Spain. OBJECTIVE: To study the incidence of all forms of tuberculosis (TB) and investigate clinical practice in TB. DESIGN: Cases of all forms of tuberculosis diagnosed in the study setting from May 1986 to April 1997 were identified though active search of different databases. Clinical and epidemiological information on cases was collected from clinical records or by interview with physicians. RESULTS: The overall incidence of all forms of tuberculosis was 38.5/100,000 and the incidence of smear-positive disease was 13.83/100,000. Most cases (97.1%) were Spanish nationals, with rates higher in men than in women (52.7/100,000 vs. 24.87/100,000) and in groups aged 25-34 and 75 years and over (61.35/100,000 and 59.35/100,000, respectively). Disseminated forms were frequent (6.6%), and the most common risk factor was human immunodeficiency virus (HIV) infection (17.7% of cases). Hospitalisation was common (71.6%). Microbiological confirmation of diagnosis was sought for 87.7% of the cases (91.8% of pulmonary vs. 75.5% of extra-pulmonary cases), and 65.2% were culture-positive (73.8% of pulmonary vs. 39.7% of extra-pulmonary cases). HIV-infected patients were treated in almost equal proportions with three or four drugs (49.7% and 48.2%, respectively), while HIV-negative cases or those whose HIV status was unknown were usually treated with three drugs. CONCLUSION: The epidemiological pattern of TB in Spain is different to other industrialised countries in the age distribution of cases and the proportions of foreigners and cases with HIV infection. Microbiological confirmation of diagnosis is more common in pulmonary than in extra-pulmonary disease, and treatment with four drugs more frequent in HIV-positive cases.

Adolescent↗

Diffractively produced charm final states in 800-GeV/c pp collisions.

We report the first observation of diffractively produced open charm in 800-GeV/c pp collisions of the type pp-->pD*X. We measure cross sections of sigma(diff)(D*+) = (0.185+/-0.044+/-0.054) (mu)b and sigma(diff)(D(*-)) = (0.174+/-0.034+/-0.029) (mu)b. Our measurements are based on 4.3x10(9) events recorded by FNAL E690 in the fixed-target run of 1991. We compare our results with previous fixed-target charm experiments.

Journal Article↗

The placental regulatory factor involved in the asymmetric IgG antibody synthesis responds to IL-6 features.

Pregnancy success is attributed to the joint action of several factors such as regulatory placental molecules and components of the mother's immune system, among others. Asymmetrical glycosilated and functionally univalent IgG antibodies are suggested to influence the immune balance between the mother and foetus, playing a meaningful role on the foetal survival in the maternal uterus. Placental secretory factors might be responsible for the increase of these molecules during gestation. Since placental factors appeared to be the inducers of these high Concanavaline A-affinity (Con-A) IgG molecules our work was focused on the identification of such factors. The chromatographic separation of placental culture supernatants (PCS) allowed the detection of fractions capable of increasing the high Con-A affinity monoclonal antibody (Mab) ratio synthesised by a hybridoma. The presence of multimeric placental forms of interleukin 6 (IL-6) could be identified in these fractions. Considering that IL-6 modulates protein glycosylation we decided to investigate its effect on the monoclonal IgG glycosylation. When placental IL-6 containing fractions or rIL-6h were added to hybridoma cultures, the proportion of asymmetric IgG antibodies increased substantially.

Animals↗

The impact of a clinical training unit on integrated child health care in Mexico.

This study had two aims: to describe the activities of a clinical training unit set up for the integrated management of sick children, and to evaluate the impact of the unit after its first four years of operation. The training unit was set up in the outpatient ward of a government hospital and was staffed by a paediatrician, a family medicine physician, two nurses and a nutritionist. The staff kept a computerized database for all patients seen and they were supervised once a month. During the first three years, the demand for first-time medical consultation increased by 477% for acute respiratory infections (ARI) and 134% for acute diarrhoea (AD), with an average annual increase of demand for medical care of 125%. Eighty-nine per cent of mothers who took their child for consultation and 85% of mothers who lived in the catchment area and had a deceased child received training on how to recognize alarming signs in a sick child. Fifty-eight per cent of these mothers were evaluated as being properly trained. Eighty-five per cent of primary care physicians who worked for government institutions (n = 350) and 45% of private physicians (n = 90) were also trained in the recognition and proper management of AD and ARI. ARI mortality in children under 1 year of age in the catchment area (which included about 25,000 children under 5 years of age) decreased by 43.2% in three years, while mortality in children under 5 years of age decreased by 38.8%. The corresponding figures for AD mortality reduction were 36.3% and 33.6%. In this same period, 11 clinical research protocols were written. In summary, we learned that a clinical training unit for integrated child care management was an excellent way to offer in-service training for primary health care physicians.

Child↗

Evolution of the lipocalin family as inferred from a protein sequence phylogeny.

The lipocalins constitute a family of proteins that have been found in eubacteria and a variety of eukaryotic cells, where they play diverse physiological roles. It is the primary goal of this review to examine the patterns of change followed by lipocalins through their complex history, in order to stimulate scientists in the field to experimentally contrast our phylogeny-derived hypotheses. We reexamine our previous work on lipocalin phylogeny and update the phylogenetic analysis of the family. Lipocalins separate into 14 monophyletic clades, some of which are grouped in well supported superclades. The lipocalin tree was rooted with the bacterial lipocalin genes under the assumption that they have evolved from a single common ancestor with the metazoan lipocalins, and not by horizontal transfer. The topology of the rooted tree and the species distribution of lipocalins suggest that the newly arising lipocalins show a higher rate of amino acid sequence divergence, a higher rate of gene duplication, and their internal pocket has evolved towards binding smaller hydrophobic ligands with more efficiency.

Amino Acid Sequence↗

A phylogenetic analysis of the lipocalin protein family.

The lipocalins are a family of extracellular proteins that bind and transport small hydrophobic molecules. They are found in eubacteria and a great variety of eukaryotic cells, in which they play diverse physiological roles. We report here the detection of two new eukaryotic lipocalins and a phylogenetic analysis of 113 lipocalin family members performed with maximum-likelihood and parsimony methods on their amino acid sequences. Lipocalins segregate into 13 monophyletic clades, some of which are grouped in well-supported superclades. An examination of the G + C content of the bacterial lipocalin genes and the detection of four new conceptual lipocalins in other eubacterial species argue against a recent horizontal transfer as the origin of prokaryotic lipocalins. Therefore, we rooted our lipocalin tree using the clade containing the prokaryotic lipocalins. The topology of the rooted lipocalin tree is in general agreement with the currently accepted view of the organismal phylogeny of arthropods and chordates. The rooted tree allows us to assign polarity to character changes and suggests a plausible scenario for the evolution of important lipocalin properties. More recently evolved lipocalins tend to (1) show greater rates of amino acid substitutions, (2) have more flexible protein structures, (3) bind smaller hydrophobic ligands, and (4) increase the efficiency of their ligand-binding contacts. Finally, we found that the family of fatty-acid-binding proteins originated from the more derived lipocalins and therefore cannot be considered a sister group of the lipocalin family.

Amino Acid Sequence↗

A cost-analysis of suspected adverse drug reactions in a hospital emergency ward.

The main objective of this study was to analyse the minimum direct cost to the Public Health System (PHS) of diagnosing and treating those patients attended to in the emergency ward (EW) for suspected adverse drug reaction (ADR). The cases were collected during March 1995 in the emergency ward of a 900-bed tertiary teaching hospital that covers 900,000 inhabitants. ADR was considered according to the WHO definition. The following EW costs were used: EW physician visit 78.5 ecus (1 ecu=156 pesetas), thorax or abdomen radiograph 21.5 ecus, computerized tomography 112.7 ecus, endoscopy 48 ecus, specialist physician visit 62 ecus. Three types of laboratory costs were considered: block of biochemical tests 16 ecus, biochemical tests with blood count 22.5 ecus, and biochemical tests with blood count and coagulation study 41.6 ecus. Pharmacotherapy of the ADR and changes in patient's usual drug therapy due to ADR were estimated. For patients admitted in the hospital, a per day cost of 391 ecus was considered. A mean ADR cost per organ or system affected (cutaneous, metabolic, gastrointestinal, nervous) was computed. The main conclusion of this study is that ADR, apart from inflicting damage on the patients, also incur PHS costs. The quantity of 42,732 ecus during the month of March, in a single hospital, can seem small when compared with the cost of some diseases such as AIDS or ischemic heart disease. But remembering that about 40% of all ADR attended to in hospitals is avoidable, a decrease of 40% could produce an annual saving of 205,216 ecus to the hospital, which is twice the annual budget of the Pharmacovigilance Centre of the Basque Country. Pharmacovigilance centres should include cost analysis of ADR among their objectives, to provide health systems managers with enough information to implement those measures that will result in a better utilization of the scarce resources of the Public Health System.

Journal Article↗

Compositional correlation between open reading frames with opposite transcriptional orientations in Escherichia coli.

This paper analyzes correlations in base composition between pairs of neighboring genes in Escherichia coli. The G + C contents of nearby, but convergently or divergently transcribed, genes show weak but significant correlations, and this is attributed to compositional variation among genomic regions. The finding that the base composition varies among intergenic regions, depending upon whether the adjacent genes are transcribed convergently, divergently, or in the same orientation, seems to indicate that transcription affects the patterns of mutation and, therefore, the overall base composition of the region.

Base Composition↗

Immunization promotion activities: are they effective in encouraging mothers to immunize their children?

Mass media communication is an important strategy for increasing parental uptake and to promote community participation when large-scale immunization activities are carried out. In Mexico, the National Vaccination Council (CONAVA) launches three immunization campaigns every year accompanied by three vaccination promotion campaigns. This study was conducted to assess whether communication activities to promote CONAVA's Second National Health Week (SNHW) were effective in providing information to mothers about the importance of immunizing their children under five years of age and in prompting them to seek immunization services. A probability sample of mothers living in the metropolitan area of Mexico City and having at least one child under five years old was selected for the study. Four outcome variables were defined as measuring the impact of the campaign: (1) mothers' knowledge about the SNHW; (2) mothers' comprehension indicating how well they understood the campaign messages (aware, partly aware and unaware); (3) mothers' motivation, i.e. whether or not they sought out immunizations for their children under the age of five and (4) mothers' opinion of how well they liked the messages. A total of 935 mothers were interviewed; 88.2% knew about the SNHW, 64.3% were aware that the campaign aimed to provide immunizations, and most held a favorable opinion about the messages. Among aware mothers, 87.5% of their children received immunizations. In this group 72.1% were prompted by the information in the campaign to seek immunizations for their children while 27.9% had to be personally invited to participate in the campaign. The latter occurred either when health workers or volunteers visited mothers in their homes or by soliciting mothers' participation as they visited or passed by immunization health posts. In the unaware mothers group, 72.7% of their children received immunizations; 62.5% of the mothers took their children because of information they received through the campaign while 37.5% had to be personally invited to immunize their children. Mothers with better socioeconomic status were more aware of the campaign, but a high percentage of them did not seek immunizations, while mothers with middle and lower socioeconomic status were motivated to immunize their children through the campaign. Promotion activities and messages communicated through the mass media were appropriate to inform and motivate mothers to seek immunization services for their children.

Adult↗

High frequency of de novo deletions in Mexican Duchenne and Becker muscular dystrophy patients. Implications for genetic counseling.

Duchenne muscular dystrophy (DMD) is the most common lethal hereditary neuromuscular disease. As there is no effective treatment, accurate carrier detection is essential for genetic counseling and prevention. Although linkage analysis has been widely used for this purpose, being an indirect analysis it has several limitations. Using linkage analysis for carrier detection, we found serious limitations, mainly because 82.9% of all proposita were isolated cases. We used quantitative polymerase chain reaction for direct carrier detection in families with exon deletions and found a higher than expected frequency of de novo deletions (62.2%). Furthermore, only 20.7% of the mothers of isolated deletion DMD/Becker muscular dystrophy (BMD) patients were found to be carriers. This result suggests that the Mexican population has a high frequency of de novo DMD mutations.

Creatine Kinase↗