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Biomedical subjects

M Irigoyen

Publications and source records attributed to M Irigoyen.

At least 19 recordsLinked to original sources
PubMed2004

Expression of SLAM as a functional and phenotypic marker in women with recurrent miscarriage.

In the present work, we investigated the Th1 and Th2 cytokine patterns secreted by infiltrating endometrial lymphocytes from fertile women and from patients with recurrent spontaneous miscarriage (RSM). Moreover, we also analyzed the expression of cytokines in the whole endometrium from fertile and RSM women. Furthermore, we investigated the expression of the activation marker signaling lymphocytic activation molecule (SLAM) a cell surface glycoprotein expressed on lymphocytes that upon engagement boosts IFN-gamma production. Our results showed a slight increase in IL-10 expression in the endometrium of some fertile women, although no significant differences were found in IFN-gamma and IL-5 expression. In contrast, analysis of IFN-gamma production by polyclonal activated lymphocytes from endometrium and/or peripheral blood from fertile women showed a significant increase compared to RSM. Analysis of SLAM protein expression in luteal phase endometrial samples showed a significant increase in the levels of the receptor in RSM women compared to fertile women. These results correlated with a significant augmentation of SLAM levels in peripheral blood T-lymphocytes from RSM patients. Interestingly, after treatment of RSM patients with paternal mononuclear cells, surface-SLAM-expression in T-cells from RSM patients significantly decreased up to levels comparable to those of fertile women. Taken together, our results suggest that endometrial cells have not a defined pattern-cytokine-production under pre-implatatory conditions, and SLAM might be a potential marker for the diagnosis of RSM and an indicator useful to follow up the patient response to allogeneic immunotherapy.

Abortion, Habitual↗
PubMed2003

Intracellular expression of CD69 in endometrial and peripheral T cells represents a useful marker in women with recurrent miscarriage: modulation after allogeneic leukocyte immunotherapy.

PROBLEM: To characterize in fertile women and women with recurrent spontaneous abortions (RSA) the expression and functional status of T cells expressing the CD69 molecule. METHOD OF STUDY: We analyzed by flow cytometry in peripheral blood and endometrium from fertile and RSA women, the surface and cytoplasmic expression of CD69 on gated T cells. In addition, we investigated by three-color flow cytometry the expression of cytokines, and subsets of memory T cells. RESULTS: In T cells, CD69 was restricted to the intracellular compartment with a higher frequency in RSA than in fertile women (68.2 +/- 12% versus 23.7 +/- 22%, P < 0.001, and 20 +/- 9.5% versus 2.1 +/- 3.8%, P < 0.005, in endometrium and peripheral blood, respectively). In contrast, the number of interferon-gamma+ (IFN-gamma+) secreting cells was higher (16 +/- 5% versus 6 +/- 1%) in fertile women. All 11 RSA women alloimmunized with parental leukocytes reached values of CD3 +/- CD69+ cells similar to those observed in fertile women. CONCLUSIONS: CD69 might represent a useful marker in the diagnosis and the follow up of RSA patients.

Abortion, Habitual↗
PubMed2000

Is the paternal mononuclear cells' immunization a successful treatment for recurrent spontaneous abortion?

PROBLEM: Alloimmunization as a treatment for recurrent spontaneous abortion (RSA) is still controversial due to the lack of enough controls to evaluate its effectiveness. The present study was conducted to compare the live birth rate in the presence or absence of immunotherapy. METHOD OF STUDY: Ninety-two women with RSA (79 primary [PA] and 13 secondary aborters[SA]) received immunotherapy. Thirty-seven RSA couples not receiving paternal alloimmunization, constituted the "control" group. RESULTS: The pregnancy rate in alloimmunized was 58 vs 46% in the control group. The live birth increased from 71% in the controls to 88% after immunotherapy. The alloimmunization induced mixed lymphocyte reaction blocking factors (MLR BFs) in 79% of women. However, they were also present in 83% of immunized women experiencing a new abortion. CONCLUSION: These results indicate that alloimmunization may be useful in the treatment of RSA.

Abortion, Habitual↗
PubMed1999

Early induction of cyclin D2 expression in phorbol ester-responsive B-1 lymphocytes.

B-1 lymphocytes represent a distinct B cell subset with characteristic features that include self-renewing capacity and unusual mitogenic responses. B-1 cells differ from conventional B cells in terms of the consequences of phorbol ester treatment: B-1 cells rapidly enter S phase in response to phorbol ester alone, whereas B-2 cells require a calcium ionophore in addition to phorbol ester to trigger cell cycle progression. To address the mechanism underlying the varied proliferative responses of B-1 and B-2 cells, we evaluated the expression and activity of the G1 cell cycle regulator, cyclin D2, and its associated cyclin-dependent kinases (Cdks). Cyclin D2 expression was upregulated rapidly, within 2-4 h, in phorbol ester-stimulated B-1 cells, in a manner dependent on intact transcription/translation, but was not increased in phorbol ester- stimulated B-2 cells. Phorbol ester-stimulated cyclin D2 expression was accompanied by the formation of cyclin D2-Cdk4, and, to a lesser extent, cyclin D2-Cdk6, complexes; cyclin D2- containing complexes were found to be catalytically functional, in terms of their ability to phosphorylate exogenous Rb in vitro and to specifically phosphorylate endogenous Rb on serine780 in vivo. These results strongly suggest that the rapid induction of cyclin D2 by a normally nonmitogenic phorbol ester stimulus is responsible for B-1 cell progression through G1 phase. The ease and rapidity with which cyclin D2 responds in B-1 cells may contribute to the proliferative features of this subset.

Animals↗
PubMed1999

Discordance between IgA switching at the DNA level and IgA expression at the mRNA level in IgA-deficient patients.

IgA deficiency is a common immune disorder in Caucasians and is associated with certain MHC conserved extended haplotypes, such as [HLA-B8, SC01, DR3], which presumably carry a susceptibility gene(s). We applied a competitive digestion-circularization PCR method to quantitate the number of switch (S)mu to S alpha rearrangements in peripheral B cells from IgA-deficient subjects homozygous for this haplotype and compared their number with the productive C alpha mRNA level to determine C alpha gene expression in IgA-switched B cells. Two types of defects, low expression of both secreted and membrane forms of productive C alpha mRNA in IgA-switched B cells and impaired IgA switching, were characterized in IgA-deficient subjects homozygous for [HLA-B8, SC01, DR3]. The former defect was also found in another noncarrier subject. It may directly cause low IgA secretion and reflects a blockade in post-IgA switch differentiation of B cells. These results suggest that the heterogeneity of defects in IgA deficiency is not simply ascribable to MHC susceptibility genes.

B-Lymphocytes↗
PubMed1999

Evaluation of household contacts of children with positive tuberculin skin tests.

BACKGROUND: Associate investigation, defined as screening the contacts of children with positive tuberculin skin tests (TST) and normal chest radiographs, has been recommended to improve case finding for active tuberculosis (TB). The success of this strategy has not been adequately studied in either adults or children. METHODS: A 2-year prospective study was conducted wherein 187 children and adolescents with infection caused by Mycobacterium tuberculosis (positive TST and normal chest radiograph) were referred to a TB Screening Clinic. An associate investigation was performed among their 659 household contacts who were interviewed to assess risk factors for TB and screened with TSTs and with chest radiographs when appropriate. RESULTS: No cases of active TB were detected, but 32% of household contacts had TSTs > or = 10 mm and were candidates for preventive therapy. Logistic regression analysis revealed that household contacts with Calmette-Guérin bacillus immunization and foreign birth were 2.26 and 3.92 times more likely (P < 0.001 and 0.002, respectively) to be tuberculin-positive. Univariate analysis of the 187 households revealed that the following risk factors present in a household member were associated with detecting a household contact with a positive TST: Calmette-Guérin bacillus immunization (P = 0.001), foreign birth (P = 0.017) and a history of having hosted foreign visitors (P = 0.032). CONCLUSION: In this Hispanic immigrant population, primarily from the Dominican Republic, screening household contacts of children with positive TSTs did not identify new cases of active TB. However, this strategy did identify household contacts who were eligible for preventive therapy.

Adolescent↗
PubMed1999

Children on the move and vaccination coverage in a low-income, urban Latino population.

OBJECTIVES: The purpose of this study was to determine the impact of childhood moves and foreign birth on vaccination coverage among Latino children in New York City. METHODS: Vaccination coverage was assessed in a survey of 314 children younger than 5 years at 2 immunization clinics. RESULTS: Forty-seven percent of the study children had moved abroad. After adjustment for health insurance, regular source of care, and country of birth, child moves had no independent effect on vaccination coverage. Foreign-born children had diphtheria-pertussis-tetanus, oral polio vaccine, and measles-mumps-rubella vaccination coverage rates similar to those of US-born children, but they were underimmunized in regard to Haemophilus influenzae type b and hepatitis B. CONCLUSIONS: Foreign birth, but not childhood moves, is a barrier to vaccinations among low-income, urban Latino children.

Adolescent↗
PubMed1998

Factors associated with Mexico City dentists' willingness to treat AIDS/HIV-positive patients.

OBJECTIVE: The purpose of this study was to investigate the characteristics and infection control practices of dentists in Mexico City in relation to their willingness to treat AIDS/HIV-positive patients. STUDY DESIGN: The population study encompassed Mexico City dentists who were selected according to a geographic criterion. A questionnaire was delivered personally to each participant, and multiple logistic regression was used for data analysis. RESULTS: A total of 598 dentists participated in the study. The response rate was 99.3% (598/602). Seventy-four percent (444) of the dentists said they would be willing to treat AIDS/HIV-positive patients. Among the variables associated with the prediction of willingness to treat these patients were glove-wearing patterns (odds ratio, 2.39; confidence interval, 1.4-4.2), types of available sterilization equipment (odds ratio = 2.42; confidence interval, 1.4-4.1), fear of losing non-AIDS/HIV-positive patients (odds ratio = 4.28; confidence interval, 2.3-8.4), and risk perception of HIV transmission (odds ratio = 2.66; confidence interval, 1.5-4.9). An interaction was found between perception of risk of HIV transmission and increase in costs (odds ratio = 3.35; confidence interval, 1.3-8.9). CONCLUSIONS: Approximately 26% of the Mexico City dentists included in the study were not willing to treat AIDS/HIV-positive patients. Educational programs aimed at misperceptions appear to be warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Studies on the structure, regulation, and pathogenic potential of anti-dsDNA antibodies.

Studies of anti-double-stranded (anti-ds)DNA antibodies have provided insights into how and why these antibodies arise in systemic lupus erythematosus. In this review we discuss the experimental approaches that have been used by our laboratory to study these autoantibodies. Structure/function analyses including site-directed mutagenesis have helped characterize the molecular genetics of anti-dsDNA antibodies, and more recently peptide libraries have been used to define molecular motifs that these antibodies bind. Most of the pathogenic anti-dsDNA antibodies observed in lupus are somatically mutated. We demonstrated in vitro and in vivo that anti-bacterial antibodies can mutate to acquire specificity for dsDNA. Furthermore, using a fusion partner constitutively expressing bcl-2, NSO(bcl-2), we have shown the existence of anergic or preapoptotic B cells making antibodies that cross-react with both bacterial antigen and dsDNA. Whether defects in the regulation of these antibodies might contribute to serum expression of anti-dsDNA antibodies in some individuals remains unknown. A major emphasis of this review is the regulation of anti-dsDNA antibodies in a transgenic mouse model harboring the gene for the heavy chain of a pathogenic anti-dsDNA antibody. Nonautoimmune transgenic mice effectively regulate autoreactive B cells by anergy and deletion, while their autoimmune counterparts do not. The vast majority of anergic B cells expressing high-affinity transgenic anti-dsDNA antibody fail to display allelic exclusion of the heavy chain. We postulate that this may be one mechanism that allows them to escape deletion. Comparative studies on light chain usage in both the autoimmune and the nonautoimmune transgenic mouse strains have demonstrated that within the autoreactive B-cell population, there are subsets that are differentially regulated. Ultimately transgenic animals making pathogenic autoantibodies may provide us with a system for testing novel therapies for autoimmune disease.

Animals↗
PubMed1997

A model to structure student learning in ambulatory care settings.

Providing students with an explicit framework for conducting patients' follow-up visits can ease students' transition into ambulatory care settings and enhance their learning. The authors describe a model that structures and defines students' tasks for a follow-up office visit. The model gives priority to the organization of patient care issues, the efficient use of patient and preceptor time, and the student's identification of a learning agenda for each patient encounter. In a rapidly expanding managed care world where physician and practice productivity are paramount, this model has the potential to enhance standardization of learning across diverse clinical sites and to increase the cost-effectiveness of teaching medical students in ambulatory settings. The authors have introduced this model in a half-day orientation for a primary care clerkship. Initial feedback suggests that the model is useful in preparing students to function more effectively in an ambulatory care setting.

Ambulatory Care↗
PubMed1996

Molecular mapping of the 8.12 SLE-associated idiotype specificity at the single amino acid level.

The 8.12 idiotype is expressed in elevated titer in the serum of patients with systemic lupus erythematosus and is a marker for a subpopulation of anti-DNA antibodies that possess a V(lambda)II encoded light chain. This study utilized a eukaryotic expression system to identify the structural basis for expression of this idiotype. Reversion of the 8.12+ DSC light chain to the hslv215.23/DPL11 germline gene reveals that the 8.12 idiotype is encoded in the germline. The 8.12+ DSC and the 8.12 AS17 light chains, both belonging to the V(lambda)II family, were subjected to site directed mutagenesis, to localize amino acids important for expression of the 8.12 idiotype. Point mutations were performed in CDR1, CDR2, FR3 and CDR3, in positions where the 8.12+ DSC differs from the 8.12-AS17. Amino acids in CDR1 and the CDR2 proximal region of FR3, but not the J proximal region of CDR3, play a crucial role in 8.12 reactivity. The 3-D structure of Mcg, a human IgG1, with which DSC shares a sequence homology of 92.3% has been examined to visualize the effect of each of the mutations and to identify the surface on DSC that comprises the idiotype.

Amino Acid Sequence↗
PubMed1995

Analysis of V kappa I and V lambda II light chain genes in the expressed B-cell repertoire.

Our previous studies of anti-DNA antibodies in SLE have demonstrated a preferential use of V kappa I and V lambda II gene families to encode light chains of antibodies that express the anti-DNA-associated 3I and 8.12 idiotypes, respectively. In this study, we employed PCR to obtain V kappa I and V lambda II germline genes from lupus patients in order to compare the germline genes to genes encoding expressed V kappa I and V lambda II light chains and to analyze the extent of somatic mutation among autoantibodies that derive from these light chain families. Our analysis shows that the germline repertoire among all persons (autoimmune and healthy) is comparable and that somatic mutation is used to diversify autoantibodies as well as anti-microbial antibodies. We have observed that autoantibodies encoded by V kappa I and V lambda II genes have a higher number of amino acid replacements in CDRs than autoantibodies encoded by other VL gene families. In addition, there may be subtle differences in V gene usage that distinguish the V kappa I-encoded light chains from other expressed V kappa light chains.

Antibodies, Antinuclear↗
PubMed1994

Dental caries status of 12-year-old students in the state of Mexico.

A total of 2275 schoolchildren 12 yr of age from the four health regions of the State of Mexico were examined for the prevalence and severity of dental caries. The proportion of caries-free children was only 10%, and the DMFS index was 6.94. 78% of the index derived from decayed surfaces, and 19% from filled surfaces. Pits and fissures of the permanent first molars were the most frequently affected surfaces. Higher dental caries scores were found in rural areas compared with the urban centers. No significant relationship was found between use of dentifrice and dental caries. Several reasons for this lack of relationship are discussed. 10% of the children account for 23% of the DMFS index. Results indicate the need to aim preventive and restorative programs at the whole population as well as at specific high risk groups or individuals.

Chi-Square Distribution↗
PubMed1994

Molecular analysis of the human immunoglobulin V lambda II gene family.

The 8.12 idiotype characterizes a subpopulation of anti-DNA antibodies in patients with systemic lupus erythematosus (SLE). The idiotype is present on lambda light chains and has previously been shown to be exclusively encoded by V lambda II light chains. RFLP analysis of the V lambda II gene family has shown the family to consist of 10 to 15 members. Thus far, the sequences of seven V lambda II germline genes are reported in the literature with one of these a pseudogene. To identify the V lambda II genes that encode 8.12 positive antibodies and to further characterize the V lambda II family, germline V lambda II clones were derived from a patient with SLE. Two libraries were constructed: a genomic DNA library and a library of PCR-derived V lambda II gene products obtained using a conserved V lambda II leader region primer and a primer for the nonamer region 3' of the coding sequence. We now describe seven new germline genes, two of which are pseudogenes. Comparison of V lambda II germline genes to sequences of 8.12 positive light chains produced by EBV-transformed B cell lines show that all 8.12 positive light chains are encoded by a limited number of highly homologous members of the V lambda II family. 8.12 negative V lambda II encoded light chains also derive from a limited number of V lambda II genes, suggesting that only a subset of the apparently available V lambda II genes are commonly expressed.

Amino Acid Sequence↗
PubMed1994

The rate of increase in blood pressure in children 5 years of age is related to changes in aerobic fitness and body mass index.

OBJECTIVE: To determine whether changes in aerobic fitness and body mass index are related to the age-related rise in blood pressure in healthy preschool children. STUDY DESIGN: Longitudinal analyses of 196 free-living children aged 5 years at baseline who were followed over a mean of 19.7 months. Aerobic fitness was assessed using a treadmill. All measures were obtained on multiple occasions at scheduled visits as part of a longitudinal cohort study. SETTING: An inner-city medical center. OUTCOME MEASURES: Blood pressure was measured using an automated Dinamap device. RESULTS: Mean systolic blood pressure was 95.3 mmHg (SD 8.38) at baseline and increased by 4.46 mmHg per year. Mean diastolic blood pressure was 53.9 mmHg (SD 5.81) at baseline and did not change significantly. Children in the highest quintile of increase in fitness had a significantly smaller increase in systolic blood pressure compared to children in the lowest quintile (2.92 vs 5.10 mmHg/year; P = .03). Children in the lowest quintile of increase in body mass index did not differ significantly in rate of increase in systolic blood pressure compared to children in the highest quintile (3.92 vs 4.96 mmHg/year). In a multiple regression model including baseline systolic blood pressure, fitness, height, body mass index, and other covariates, greater increase in fitness (P = .03) and lesser increase in body mass index (P < .01) were associated with lower rates of increase in systolic blood pressure. In a similar multivariate analysis, an increase in fitness was also associated with a lower rate of increase in diastolic blood pressure (P = .02). CONCLUSION: Young children who increase their aerobic fitness or decrease their body mass index reduce the rate of the age-related increase in blood pressure. These observations may have implications for development of interventions directed at the primary prevention of hypertension.

Age Factors↗