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Genetic thrombophilic mutations among couples with recurrent miscarriage.

BACKGROUND: Some cases of recurrent first trimester miscarriage (RM)-the loss of three or more consecutive pregnancies at <12 weeks' gestation-have a thrombotic aetiology. METHODS: We determined (i) the prevalence of three thrombophilic mutations [factor V Leiden (FVL), prothrombin G20210A (PTG) and methylenetetrahydrofolate reductase (MTHFR) C677T] amongst 357 Caucasian couples with RM and 68 parous Caucasian couples with no history of miscarriage and (ii) the prospective outcome of untreated pregnancies amongst couples with RM in which either partner carried a thrombophilic mutation. RESULTS: The allele frequencies of FVL (2%), PTG (2%) and MTHFR C677T (31%) were similar between cases and controls. The prevalence of multiple thrombophilic mutations (greater than one mutation) was also similar between cases and controls. Amongst couples in whom either partner carried greater than one thrombophilic allele, the relative risk of miscarriage in a future untreated pregnancy was 1.9 (95% confidence interval, 1.3-2.8) compared with those couples who carried no thrombophilic mutation. CONCLUSION: The prevalence of thrombophilic mutations is similar in couples with RM and parous controls. In couples with RM, multiple genetic thrombophilic mutations in either partner significantly increases the risk of miscarriage in a subsequent pregnancy.

Abortion, Habitual↗

Some psycho-social consequences of multiple sclerosis: problems of social interaction and group identity.

The study was concerned with the psycho-social consequences for married couples of multiple sclerosis being contracted by one of the partners. In particular, problems of social interaction and group identity were explored. In determining their mode of interaction with healthy people such couples can choose between normalizing, i.e. endeavouring to carry on their relationships with other people according to their pre-illness pattern, or of disassociating, i.e. turning away from former associates and seeking a new peer group among others with like affliction. In nearly every case husband and wife agreed on the choice of stratagem, a majority of the couples forming the sample opting for disassociation. Membership of the Multiple Sclerosis Society was much more usual among the disassociating couples than among those 'normalizing'. The variables of age, sex, social class and severity of illness were not found to affect the mode of interaction, whereas place of residence and medical interest in them, as perceived by patients and their spouses, were influencing factors.

Adult↗

Life events and peer substance use and their relation to substance use problems in college students.

Substance use disorders among college students are not well understood, and the present study examined the relationship of two environmental factors to alcohol and drug use problems in 616 (316 women) college students. Participants completed measures assessing substance use problems, life events, and substance use among peers. Alcohol use problems were significantly associated with higher drug use problems and regular use of illicit drugs among friends. Drug use problems were significantly associated with male gender, higher alcohol use problems, regular use of alcohol and drugs among friends, illicit drug use among romantic partners, and higher numbers of negative life events. Results extend previous research and suggest that college students who experience multiple negative life events and/or affiliate with substance using friends and romantic partners may be at risk for developing a substance use problem.

Adolescent↗

Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma.

In multiple myeloma, karyotopic 14q32 translocations have been identified at a variable frequency (10-60% in different studies). In the majority of cases, the partner chromosome has not been identified (14q+), and in the remaining cases, a diverse array of chromosomal partners has been implicated, with 11q13 being the most common. We developed a comprehensive Southern blot assay to identify and distinguish different kinds of immunoglobulin heavy chain (IgH) switch recombination events. Illegitimate switch recombination fragments (defined as containing sequences from only one switch region) are potential markers of translocation events into IgH switch regions and were identified in 15 of 21 myeloma cell lines, including seven of eight karyotyped lines that have no detectable 14q32 translocation. From all nine lines or tumor samples analyzed further, cloned illegitimate switch recombination fragments were confirmed to be IgH switch translocation breakpoints. In three of these cases, the translocation breakpoint was shown to be present in the primary tumor. These translocation breakpoints involve six chromosomal loci: 4p16.3 (two lines and the one tumor); 6; 8q24.13; 11q13.3 (in three lines); 16q23.1; and 21q22.1. We suggest that translocations into the IgH locus (i) are frequent (karyotypic 14q32 translocations and/or illegitimate switch recombination fragments are present in primary tumor samples and in 19 of 21 lines that we have analyzed); (ii) occur mainly in switch regions; and (iii) involve a diverse but nonrandom array (i.e., frequently 11q13 or 4p16) of chromosomal partners. This appears to be the most frequent genetic abnormality in multiple myeloma.

Base Sequence↗

Microsurgical vasovasostomy versus microsurgical epididymal sperm aspiration/testicular extraction of sperm combined with intracytoplasmic sperm injection. A cost-benefit analysis.

PURPOSE: Vasovasostomy (VVS) represents the standard therapy of choice for the treatment of obstructive azoospermia following vasectomy. However, recently, intracytoplasmic sperm injection (ICSI) has been suggested by some to represent the solution for all cases of malefactor infertility regardless of its etiology based on its success rates. Therefore, we compared VVS to microsurgical epididymal sperm aspiration (MESA)/testicular extraction of sperm (TESE) and ICSI in terms of pregnancy, complications, and costs. PATIENTS AND METHODS: Between 1/93 and 6/98, 157 VVS were performed microsurgically using the double-layer technique. Between 9/94 and 9/97, 69 and 42 couples underwent MESA/ICSI and TESE/ICSI, respectively, for epididymal obstruction and azoospermia of testicular origin. RESULTS: The mean interval of vasal obstruction was 7.6 (0.5-18) years; patency after VVS was 77%, pregnancy rate was 52%. Local complication rate was 4.7%, no major complications were observed. Costs per life birth after VVS were 5,447 DM or 2,793 Euro. Pregnancy rates after MESA/TESE and ICSI were 22.5 and 19.5%, respectively, with 16 singletons, 3 twins and 3 abortions; local complications occurred in 3.9% of the men. Multiple births were noticed in 15.8% following ICSI, but in only 0.7% following VVS. 5.7 and 1.4% of the female partners experienced serious complications (mild or severe ovarian hyperstimulation syndrome, respectively). Costs per life birth after a MESA/TESE cycle amounted to 28,804 DM or 14,547 Euro. CONCLUSIONS: Even in the era of ICSI, microsurgical VVS represents the standard approach for obstructive azoospermia following vasectomy. Based on a cost-benefit analysis, VVS is more successful in terms of pregnancy rates (52 vs. 22.5%). VVS does not expose the female partners to complications following treatment of male infertility. In contrast to ICSI, multiple birth rates do not increase after VVS. We conclude that MESA/ICSI should be reversed for patients who are not amenable for microsurgical reconstruction.

Adult↗

CLOE: identification of putative functional relationships among genes by comparison of expression profiles between two species.

BACKGROUND: Public repositories of microarray data contain an incredible amount of information that is potentially relevant to explore functional relationships among genes by meta-analysis of expression profiles. However, the widespread use of this resource by the scientific community is at the moment limited by the limited availability of effective tools of analysis. We here describe CLOE, a simple cDNA microarray data mining strategy based on meta-analysis of datasets from pairs of species. The method consists in ranking EST probes in the datasets of the two species according to the similarity of their expression profiles with that of two EST probes from orthologous genes, and extracting orthologous EST pairs from a given top interval of the ranked lists. The Gene Ontology annotation of the obtained candidate partners is then analyzed for keywords overrepresentation. RESULTS: We demonstrate the capabilities of the approach by testing its predictive power on three proteomically-defined mammalian protein complexes, in comparison with single and multiple species meta-analysis approaches. Our results show that CLOE can find candidate partners for a greater number of genes, if compared to multiple species co-expression analysis, but retains a comparable specificity even when applied to species as close as mouse and human. On the other hand, it is much more specific than single organisms co-expression analysis, strongly reducing the number of potential candidate partners for a given gene of interest. CONCLUSIONS: CLOE represents a simple and effective data mining approach that can be easily used for meta-analysis of cDNA microarray experiments characterized by very heterogeneous coverage. Importantly, it produces for genes of interest an average number of high confidence putative partners that is in the range of standard experimental validation techniques.

Animals↗

The BCL6 gene in B-cell lymphomas with 3q27 translocations is expressed mainly from the rearranged allele irrespective of the partner gene.

The BCL6 gene, which functions as a transcription repressor, is the target of multiple chromosomal translocations in non-Hodgkin's lymphomas (NHL). These translocations occur in the nontranslated region of the BCL6 gene, juxtaposing regulatory sequences of the diverse partner genes to the open reading frame of the BCL6 gene and thus are thought to deregulate BCL6 gene expression. The levels of expression of the BCL6 gene and protein have been demonstrated to predict the clinical outcome of diffuse large B-cell lymphomas. By contrast, the prognostic significance of BCL6 gene translocations is unclear. In this study we have sought an explanation for this apparent discrepancy. We examined tumors with a variety of different BCL6 translocations and therefore with a variety of potentially substituted promoters. We found no increase in total BCL6 mRNA levels in the NHL specimens harboring BCL6 gene translocation. Indeed, some of these tumors expressed relatively low quantities of the BCL6 mRNA. We also sought to determine whether BCL6 transcription occurs from the rearranged or from the normal untranslocated allele in these tumors. We demonstrate that lymphoma cell lines and majority of NHL tumor specimens expressed BCL6 mRNA predominantly from the rearranged allele that may come under the control of various partner gene promoters. However, few NHL tumors with BCL6 gene translocations expressed BCL6 mRNA equally from the rearranged and the nonrearranged alleles. Neither the nature of the substituted promoters nor the presence of activating mutations in the BCL6 regulatory sequences correlated with the allelic expression of the BCL6 gene in these tumors.

Alleles↗

Preventive counseling of HIV-positive men and self-disclosure of serostatus to sex partners: new opportunities for prevention.

This study examined whether preventive counseling of HIV-positive men (N = 255) was associated with self-disclosure of serostatus to sex partners. Men who reported being counseled at posttest and at their current HIV clinic to disclose their serostatus to partners were more likely to have done so than men counseled only at posttest, only at the HIV clinic, or not counseled at either site. Disclosure increased with the number of times counseled at the HIV clinic. These patterns held for HIV-negative partners, but not for HIV-positive or HIV-unknown partners. Disclosure to HIV-negative partners was associated with safer sexual practices. The findings suggest that counseling interventions for HIV-positive men, when delivered by multiple sources, may provide an effective means of increasing disclosure to sexual partners.

Adult↗

Risk factors for multiple gestation in women undergoing intrauterine insemination with ovarian stimulation.

OBJECTIVE: To identify whether sperm characteristics after washing and/or ovulation induction cycle characteristics can predict the occurrence of multiple conception in patients undergoing ovarian stimulation and IUI. DESIGN: Retrospective study. SETTING: A gynecology clinic and an andrology laboratory at a tertiary care facility. PATIENT(S): One hundred patients with single pregnancies and 22 patients with multiple pregnancies. INTERVENTION(S): Patients underwent ovarian stimulation and IUI with their partner's sperm. MAIN OUTCOME MEASURE(S): Relation of patient characteristics, ovarian stimulation, and sperm characteristics after washing to the occurrence of multiple pregnancy. RESULT(S): The mean serum E2 level on the day of hCG injection was significantly higher in the multiple conception group, but the number of follicles was not. The total sperm count, total motile sperm count, and sperm motility after washing did not differ between the groups. However, couples with multiple pregnancies had sperm with a significantly higher amplitude of lateral head movement than couples with single pregnancies. A peak E2 level of >583 pg/mL on the day of hCG injection and sperm with an ALH of >4 microm after washing predicted the occurrence of multiple pregnancy. CONCLUSION(S): Sperm with an amplitude of lateral head movement of >4 microm and a peak E2 level of >583 pg/mL are significant risk factors for multiple pregnancy in patients undergoing IUI.

Adult↗

Behavior problems among preschool children born to adolescent mothers: effects of maternal depression and perceptions of partner relationships.

Investigated how maternal depression influenced the relation between mothers' perceptions of the quality of their partner interactions and behavior problems among their preschool children. Participants included 194 low-income families from 4 sites. Approximately three fourths of the mothers (72%, n = 139) identified a male partner and comprised the analysis sample. Mothers were adolescents (< or = age 19) at delivery, and data were gathered when children were 4 to 5 years of age. In this high-risk sample, 42.4% of the children had been maltreated, 36% had externalizing scores in the clinical range, and 10.8% had internalizing scores in the clinical range. Multiple regression analyses revealed (a) maternal perceptions of negative partner interactions were associated with more internalizing behavior problems among the children, adjusting for the effects of maltreatment; (b) maternal depression mediated the relation between the maternal perceptions of the quality of partner interactions and children's internalizing and externalizing behavior problems; and (c) maternal perceptions of positive partner interactions did not protect children from internalizing or externalizing behavior problems associated with maltreatment. Programs for adolescent mothers should provide screening and treatment for depressive symptoms and help partners negotiate caregiving roles and mutually satisfying relationships.

Adolescent↗

Spontaneous cessation of smoking and alcohol use among low-income pregnant women.

BACKGROUND: Despite the strong evidence of harmful effects, tobacco and alcohol use during pregnancy continue to be major public health challenges. Some women, however, do stop spontaneously when they learn of their pregnancy. No study has investigated spontaneous cessation of both behaviors in a low-income predominantly unmarried U.S. population. OBJECTIVE: To describe the prevalence of spontaneous cessation of cigarette and alcohol use alone and in combination and associated factors among low-income pregnant women. METHODS: Subjects (N=601) were currently smoking or smoking when they became pregnant and participating in Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) programs in the greater Boston, Massachusetts, area. Baseline interviews assessed the factors being studied and the spontaneous cessation of cigarette and alcohol use with pregnancy. Saliva cotinine verified self-reported smoking status. RESULTS: Spontaneous cessation of smoking and alcohol use was reported by 28% and 80% of the women, respectively; 25% spontaneously quit both, and 15% stopped neither. Multivariable analyses indicated that smoking cessation was less likely in women who had previous births, had a husband or partner who smoked, were born in the United States, were black (non-Hispanic, non-Portuguese), had less than a high school education, were highly addicted, reported lower perceived risk to the fetus, and reported "too many other problems in life to stop." Hispanic ethnicity, younger age, and more social support to quit smoking were related to spontaneous alcohol abstinence. CONCLUSIONS: Targeted multiple strategies, including those aimed at increasing participation of partners, are needed for low-income pregnant smokers.

Adult↗

Trade-offs in avian parental care: a review of theory and meta-analysis of brood size manipulations.

The selective forces shaping parental care have been studied for over 50&#x2009;years. While theoretical and experimental work has yielded qualitative progress, the large body of empirical work testing predictions about parental investment based on life-history trade-offs has yet to be synthesized. We first provide an overview of the core life-history theory exploring how selection might shape parental care. We then conduct a systematic review and meta-analysis on studies that experimentally manipulated brood size in birds, a widely used experimental approach to manipulate parental investment. We extracted 313 estimates from 62 studies representing 31 species of birds from 19 different families and tested key predictions on trade-offs in parental care derived from theory. Our analysis provides strong support for some predictions about life-history trade-offs in parental care, but weak or equivocal support for others. Specifically, we found that overall, avian parents respond to brood size manipulations as predicted by life-history theory: they increased care in response to brood enlargement, and decreased care in response to brood reductions. Furthermore, for the same relative manipulation size, responses to brood reductions were greater than responses to brood enlargements. This finding is consistent with predictions derived from life-history theory based on some types of non-linear utility curves. However, many predictions derived from theory are not well supported by our comparative analysis. Species' life-history traits such as clutch size (a measure of current reproduction), adult survival, and broods per year (two measures of future reproduction), explained little, if any, among-species variation in response to brood size manipulations. Several factors may explain this. We highlight that brood size manipulations may affect more than just perception of the value of current reproduction, such as altering parents' perception of predation risk. Importantly, these unintended consequences could lead to asymmetric responses like those we observed. Other common experimental approaches - such as hormone manipulations, altering a partner's effort, and food supplementation - often affect multiple traits or fitness components simultaneously, or may involve cues that poorly match the evolved mechanisms guiding parental behaviour. Our review of both theory and experimental approaches suggests that there are multiple opportunities for more precise experiments. We offer several recommendations for effective designs. One is improved understanding of the biology underlying the functions relating to costs and benefits, with careful consideration of not only how the manipulation will affect only one of those, but also the mechanisms that might alter how parents perceive the manipulation. We also emphasize general principles, such as assessing alternative hypotheses and devising multiple independent tests. Armed with these recommendations, we believe there are new opportunities to increase the strength of inference achieved from studies aimed at understanding the trade-offs affecting the evolution of parental care.

Animals↗

The cytology of the gametes and fertilization of Allomyces macrogynus.

The gametes and the process of fertilization were examined by light and electron microscopy in the lower eukaryote Allomyces macrogynus. Differences in gamete morphology included the overall larger size and the presence of a larger nuclear apparatus, along with the association of a side-body complex and many more mitochondria in the female gamete. In this species of Allomyces, fertilization was initiated by contact and fusion of specialized regions of the gamete plasma membranes resulting in a binucleate fusion cell surrounded by plasma membrane contributed by both partners. Following plasmogamy, nuclear fusion was initiated by multiple nuclear membrane contacts between adjacent outer membranes. Following inner membrane fusion, small nucleoplasmic bridges were observed which presumably fused with one another and resulted in a single bridge which widened, forming the mature diploid nucleus. After karyogamy, fusion of the nuclear caps did not always occur and zygotes with and without fused caps were observed. Coalescence of the nucleoli completed the events of fertilization, forming zygote with a single nuclear apparatus (sometimes with two caps) and two flagella. These observations are discussed in relation to fertilization mechanisms and compared to fertilization in other organisms.

Cell Fusion↗

[ZAP genes: characterizing the protein structure of a new family of proliferation associated genes in the exocrine pancreas].

While interested in proliferation-dependent gene regulation in a pancreatic carcinoma cell line, we cloned a set of proteins (ZAP) characterized by a conserved region consisting of consecutive zinc finger, ankyrin repeat and PH domains. Functional aspects of these domains were obtained by comparison with proteins involved in several signal transduction pathways and cell cycle regulation. The members of the ZAP protein family are individually characterized by different types of supplementary protein domains, their chromosomal localization and their tissue specific gene transcription. All results indicate a wide spectrum of protein-protein interactions. Up to now specific binding partners have not been identified. In summary, the multiplicity of conserved regions and transcriptional data indicate a scaffold function for ZAP proteins in the complex network of proliferation associated intracellular signal transduction pathways.

Amino Acid Sequence↗

Genital chlamydial infections: epidemiology and reproductive sequelae.

Genital chlamydial infection is increasing and is now more common than gonorrhea. A sizable percentage of chlamydial infections of the lower genital tract in women progress to endometritis and salpingitis. Tubal infertility and ectopic pregnancy are important sequelae. Failure to control chlamydial infections reflects the following four factors: (1) Many cases are mild or asymptomatic; (2) diagnostic tests are expensive and technically demanding; (3) at least 7 days of multiple-dose therapy are currently required; and (4) partner notification is not routinely performed. Thus early identification of infected persons and compliance with curative therapy are less likely than with other sexually transmitted bacterial diseases.

Acute Disease↗

alphaII-Spectrin interacts with five groups of functionally important proteins in the nucleus.

Nonerythroid alpha-spectrin (alphaSpIISigma( *)) is a structural protein that has been identified in the nucleus of mammalian cells and shown to be involved in DNA repair. It is also deficient in cells from the clinically diverse genetic disorder Fanconi anemia (FA). In order to get a clearer understanding of the role of alphaSpIISigma( *) in DNA repair, and whether it may have other important functions in the nucleus, studies were undertaken to identify specific alphaSpIISigma( *) protein binding partners in the nucleus. The results demonstrate that multiple proteins co-immunoprecipitate with alphaSpIISigma( *) from nuclear extracts from normal human lymphoblastoid and HeLa cells. These can be grouped into five categories: structural proteins, proteins involved in DNA repair, chromatin remodeling proteins, FA proteins, and transcription and RNA processing factors. These studies indicate that alphaSpIISigma( *) may play a role in a number of diverse and important processes in the nucleus and that a deficiency in this protein, as occurs in FA, could affect a number of critical cellular pathways.

Cell Nucleus↗

Evaluation of a cognitive-behavioral, group, randomized controlled intervention trial to prevent sexually transmitted infections and unintended pregnancies in young women.

BACKGROUND: Few cognitive-behavioral interventions have focused on preventing sexually transmitted infections (STIs) and unintended pregnancies (UPs) in young, sexually active women in a single study. Military recruit training provides a well-defined, national, nonclinic sample in which to evaluate such an intervention. METHODS: All female Marine recruits (N=2,288) in training were approached. Of these, 2,157 (94.3%) voluntarily agreed and were randomly assigned, by platoons, to participate in cognitive-behavioral interventions to prevent STIs or UPs or to prevent physical training injuries and cancer. Participants completed self-administered questionnaires and were screened for pregnancy, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis at baseline and, on average, 1 and 14 months postintervention. RESULTS: A higher proportion of the control group had a postintervention STI or UP [odds ratio (OR)=1.41, 95% confidence interval (CI)=1.01-1.98]. Among participants who had no history of STIs or pregnancy, but who engaged in risky sexual behaviors just before recruit training, the control group was more likely to acquire a postintervention STI (OR=3.24, CI=1.74-6.03). Among participants who were not sexually experienced at baseline, the control group was more likely to have casual (OR=2.05, 95% CI=1.04-4.08) and multiple (OR=1.87, 95% CI=1.01-3.47) sexual partners postintervention. CONCLUSIONS: This randomized controlled trial indicates that cognitive-behavioral interventions are effective for reducing behavioral risk and preventing STIs and UPs in young, sexually active women who are not seeking health care.

Adult↗

Phenotypic and genetic heterogeneity of familial hyperkalaemic hypertension (Gordon syndrome).

1. Familial hyperkalaemic hypertension (FHH), also called pseudohypoaldosteronism type II (PHA2) or Gordon syndrome, is a rare Mendelian-form of low-renin hypertension. The first cases of FHH were reported approximately 30 years ago and they described the peculiar biochemical abnormalities (i.e. hyperkalaemia and hyperchloraemic acidosis despite a normal glomerular filtration rate). 2. Since then, more than 90 single cases and families have been reported in the literature. These various reports show marked differences in phenotype. 3. Our group has now collected 14 unrelated pedigrees originating from different parts of France and Europe. We confirm the large variations in the age of discovery and in the severity of the biochemical abnormalities from one individual to another and from one family to another one. 4. Blood pressure levels have no significant relationship with hyperkalaemia or hyperchloraemia, but there is a positive relationship with age, as in the normal population. 5. Analyses of clinical features and Mendelian segregation in our families demonstrate autosomal-dominant inheritance, as expected from the literature. 6. Efforts have been made in the past years to unravel the gene responsible for the disease. Until now, a primary responsibility of the gene encoding the thiazide-sensitive Na-Cl cotransporter (SLC12A3) has been excluded in PHA2 families. Three loci have been identified on chromosomes 1 (PHA2A), 17 (PHA2B) and 12 (PHA2C). 7. More recently, analysis of three additional pedigrees, including 10 affected subjects, with over 25 members allowed us to demonstrate further genetic heterogeneity and the existence of at least a fourth locus. 8. The genetic heterogeneity of this syndrome, and thus the variety of molecular defects, suggests the role of either several new components of the same pathway, multiple aldosterone- regulated effectors or direct or indirect partners of the Na-Cl cotransporter.

Adolescent↗