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Biomedical subjects

N Markovic

Publications and source records attributed to N Markovic.

At least 19 recordsLinked to original sources
PubMed2006

Relationships between maternal plasma leptin, placental leptin mRNA and protein in normal pregnancy, pre-eclampsia and intrauterine growth restriction without pre-eclampsia.

Leptin, an adipocyte hormone involved in energy homeostasis, is important in reproduction and pregnancy. Questions yet to be addressed include the source of higher leptin during pregnancy and its relationship to pregnancy outcome and fetal growth. The objective of this study was to investigate the relationship between placental leptin gene expression, placental leptin protein concentration and maternal plasma leptin concentration among control pregnant women, women with pre-eclampsia and women with growth-restricted infants. We also investigated the relationship between placental leptin expression and the placental expression of enzymes involved in cellular lipid balance: fatty acid translocase (CD36), carnitine palmitoyltransferase I (CPT-1B) and lipoprotein lipase (LPL). Placental leptin expression, placental protein and maternal plasma concentration were higher in pre-eclampsia than in controls but not in women with growth-restricted infants. Placental leptin expression and placental protein were higher in the preterm pre-eclamptic subjects, whereas maternal leptin was higher in the term pre-eclamptic subjects. The placental gene expression of CD36, CPT-1B and LPL were not different among the groups. This study suggests that despite similar failed placental bed vascular remodelling in pre-eclampsia and intrauterine growth restriction (IUGR), leptin gene expression is higher only in preterm pre-eclampsia.

Adult↗
PubMed2005

Expression of von Hippel Lindau (pVHL) protein in placentae from normal pregnant women and women with preeclampsia.

The hypoxia inducible transcription factors, HIF-1alpha and -2alpha proteins, are overexpressed in placentae from women with preeclampsia (Biol Reprod 2001;64:499-506; Biol Reprod 2001;64:1019-1020). Normally, these proteins are regulated in an oxygen-dependent manner being rapidly degraded by the ubiquitin-mediated proteasomal pathway. Recent studies have shown that the tumor suppressor protein, von Hippel Lindau (VHL), targets HIF for ubiquitinylation under nonhypoxic conditions. The objectives of the present work were: (1) to investigate VHL protein expression in normal pregnant (NP), preeclamptic (PE), and preterm (without PE) placentae, (2) to test whether VHL protein is hypoxia inducible in term and first trimester placental villous explants, and (3) to analyze the ontogeny of VHL protein expression in the human placenta. To begin evaluating the potential contribution of VHL to HIF overexpression in preeclamptic placentae, we analyzed the levels of the VHL protein in both normal and preeclamptic placentae (n=7 each). We hypothesized a deficiency of VHL protein in preeclamptic placentae. Eight biopsy sites were tested in each placenta and protein extracts were made. Western analysis was performed using VHL specific antibodies. Human renal adenocarcinoma (ACHN) cell extracts and extracts from COS-7 cells transfected with a VHL expression vector were used as positive controls. In a total of 112 biopsy sites that were analyzed (56 each for normal and preeclamptic placentae), the composite densitometry ratios (PE/NP) for the long (28 kDa) and short (19 kDa) forms of VHL were 1.09+/-0.2 and 1.16+/-0.11, respectively (both p=NS vs 1.0). A ratio of 1.0 indicates equal expression by preeclamptic and normal placentae. The same placentae exhibited composite densitometry (PE/NP) ratios of 1.97+/-0.23 and 1.68+/-0.20 for HIF-1alpha and -2alpha proteins, respectively (both p<0.05 vs 1.0). In a separate analysis, the protein expression of the short form of VHL was also comparable among NP, PE and preterm (n=6) placentae. VHL immunoreactivity was localized to cells within the basal plate and the syncytiotrophoblast. Despite induction of HIF proteins by hypoxia in first and term villous explants, there was no significant upregulation of VHL proteins. Finally, the expression of both the short and long forms of VHL protein decreased with gestational age (both p<0.05 by ANOVA), and in villous tissue from first trimester placentae VHL immunoreactivity was predominantly localized to the cytotrophoblast. These results suggest that (1) deficiency of VHL protein does not account for HIF-alpha overexpression in preeclamptic placentae, (2) VHL protein is not regulated by hypoxia in either first trimester or term placental villous explants, and (3) VHL protein expression in the placenta decreases as a function of gestational age.

Adult↗
PubMed2005

Extra-placental expression of vascular endothelial growth factor receptor-1, (Flt-1) and soluble Flt-1 (sFlt-1), by peripheral blood mononuclear cells (PBMCs) in normotensive and preeclamptic pregnant women.

The soluble VEGF receptor, sFlt-1 (otherwise referred to as sVEGFR-1), has been implicated in the pathogenesis of preeclampsia. The preeclamptic placenta has been previously demonstrated to produce high levels of the soluble VEGF receptor. Here we tested the hypothesis that peripheral blood mononuclear cells (PBMCs) may also represent an additional source for circulating sFlt-1 during normal and preeclamptic pregnancies. We first demonstrate that preeclamptic placentae show five-fold increased Flt-1 and sFlt-1 mRNA levels. We also show that the Flt-1 and sFlt-1 levels are eight-fold higher in preeclamptic placentae if we collect biopsies without rinsing them in saline to remove excess blood. Cultured villous explants from women with preeclampsia failed to show the increased amount of Flt-1 and sFlt-1 mRNA that was observed in the placental biopsies of normal pregnancy and preeclampsia. Under normoxic conditions the Flt-1 and sFlt-1 mRNA levels in the explants were 3.11+/-0.6 fold in normal pregnancy and 3.6+/-0.4 fold in women with preeclampsia (p = NS by ANOVA). However, the same villous explants showed hypoxic induction of Flt-1 mRNA (NP 3.96+/-0.4 fold, p = NS and PE 5.24+/-0.6 fold, p < 0.05 by ANOVA). We analyzed Flt-1 and sFlt-1 protein levels in the peripheral blood mononuclear cells (PBMCs) to analyze the possibility of an extra-placental sFlt-1 source. Our results indicate that PBMCs of pregnant women are capable of expressing variable amounts of Flt-1 proteins. PBMCs from pregnant women exposed to hypoxia show up-regulation of HIF-1alpha and Flt-1 proteins. PBMCs obtained from women with preeclampsia (n = 9) produced significantly higher amounts of sFlt-1 under normal tissue culture conditions (104.6+/-14.3 pg/ml vs. 46.23+/-5.03 pg/ml, p < 0.05 by ANOVA) and much higher concentrations under hypoxia (196.74+/-26.3pg/ml vs. 83.3+/-13.6pg/ml, p < 0.05 by ANOVA) than PBMCs from normal pregnant women (n = 11). Moreover, analysis of PBMCs from a different group of women with a history of preeclampsia showed persistent abnormality of Flt-1 women one year post-partum. The present study indicates that Flt-1 dysregulation in PBMCs of pregnant women resulting in over-expression of sFlt-1 could be an additional (extra-placental) source of sFlt-1 that contributes to the pathogenesis of preeclampsia.

Adult↗
PubMed2003

Estimating the lesbian population: a capture-recapture approach.

STUDY OBJECTIVE: Little is known about the number of women who identify as lesbian. Estimates from the US range from 1% to nearly 10%. Accurate estimates are critical in order to meet lesbian's healthcare needs and to address health problems that may be more prevalent among them. This study used capture-recapture methods to estimate the lesbian population of Allegheny County, Pennsylvania. DESIGN: Mailing lists from four sources were used to identify lesbians. The capture-recapture method and log-linear modelling were used to estimate the number of lesbians in the defined geographical area, and the percentage of the female population they comprised there was determined through census data. SETTING: Allegheny County, Pennsylvania, USA. RESULTS: A total of 2185 unique names were identified. The capture-recapture method estimated that the total lesbian population of Allegheny County was 7031 (95% CI 5850 to 8576). Therefore, based on the 1990 census figures, the county's adult lesbian population was estimated to be 1.87% (95% CI 1.56% to 2.28%) of the adult female population. CONCLUSIONS: An estimate of the lesbian population is fundamental for addressing lesbian's health needs and for developing appropriate research programmes. Capture-recapture methods have the potential to provide accurate and reliable estimates of this population in any location.

Adult↗
PubMed2001

Quantum phase slips in superconducting nanowires.

We have measured the resistance vs temperature of more than 20 superconducting nanowires with nominal widths ranging from 10 to 22 nm and lengths from 100 nm to 1 microm. With decreasing cross-sectional areas, the wires display increasingly broad resistive transitions. The data are in very good agreement with a model that includes both thermally activated phase slips close to T(c) and quantum phase slips (QPS) at low temperatures, but disagree with an earlier model based on a critical value of R(N)/R(q). Our measurements provide strong evidence for QPS in thin superconducting wires.

Journal Article↗
PubMed2001

A novel X chromosome-linked genetic cause of recurrent spontaneous abortion.

OBJECTIVE: Unexplained recurrent spontaneous abortion is a common women's health problem that affects approximately 1 of every 200 women who wish to have children. It has long been assumed that a large proportion of recurrent spontaneous abortion results from genetic problems, but no causative genes have been identified to date. Here, we tested the hypothesis that a subset of women with recurrent spontaneous abortion are carriers of X-linked recessive disorders that result in the loss of male pregnancies. STUDY DESIGN: X chromosome inactivation patterns, an assay used to detect women who are likely to be carriers of X-linked recessive cell-lethal traits, were compared between 105 female patients with idiopathic recurrent pregnancy loss and 101 women (control subjects) with a single successful pregnancy and no history of pregnancy loss. Inheritance patterns and gender of offspring were studied in relevant subsets of participants. RESULTS: Female patients showed a highly statistically significant increase in the frequency of skewed X chromosome inactivation (90%; P < .0005). Female patients with highly skewed X chromosome inactivation showed a significant decrease in male children. Four of 6 families that were studied showed maternal inheritance of the skewed inactivation trait. CONCLUSION: We found the 14% of women with unexplained recurrent pregnancy loss show highly skewed X inactivation, which suggests that they are carriers of X-linked recessive lethal traits. Furthermore, the observed gender bias among women with highly skewed X inactivation suggests selective loss of male conceptions, which is consistent with an X chromosome-linked genetic defect that leads to cell death or growth disadvantage. Identification of such female carriers is important for the reproductive counseling and treatment of these women.

Abortion, Habitual↗
PubMed2001

Selective overexpression of the hypoxia-inducible transcription factor, HIF-2alpha, in placentas from women with preeclampsia.

Transcription factors orchestrate the development of extraembryonic tissues. Because placental hypoxia likely plays an important role in both normal and abnormal placentation, we have been investigating the hypoxia-inducible transcription factors (HIFs) in the human placenta. In this report, we focus on the placentas from women with preeclampsia. Because the placenta is a large, heterogeneous organ, we employed a systematic and unbiased approach to placental sampling, and our results are based on the analyses of eight biopsy sites per placenta. We observed no significant differences in HIF-1alpha or -2alpha mRNA expression between normal term and preeclamptic placentas. Nor was HIF protein expression significantly different, with the notable exception of HIF-2alpha, which, on average, was increased by 1.7-fold in the preeclamptic placentas (P: < 0.03 vs. normal term placentas). Considering all 48 paired placental biopsy sites (eight sites each for six normal term and six preeclamptic placentas), HIF-2alpha protein levels in the preeclamptic placentas exceeded those in the normal term placentas in 39, or 81%, of the paired sites (P: < 0.0013). The HIF-2alpha immunoreactivity was mainly located in the nuclei of the syncytiotrophoblast and fetoplacental vascular endothelium in the preeclamptic villous placenta. To control for the earlier gestational age of the preeclamptic placentas, an additional group of placentas from preterm deliveries without preeclampsia were also evaluated. The HIF protein expression was comparable in these preterm specimens and the normal term placentas. We conclude that protein expression of HIF-2alpha, but not of HIF-1alpha or -1beta, is selectively increased in the preeclamptic placenta. The molecular mechanism(s) of this abnormality as well as the genes affected downstream are currently under investigation. To our knowledge, this is the first report of abnormal HIF-2alpha expression in human disease other than cancer.

Adult↗
PubMed2001

Physical activity and cardiovascular risk factors in a developing population.

PURPOSE: Noncommunicable diseases are emerging in developing countries. However, few studies have been conducted in those countries to evaluate the role of physical activity in the development of cardiovascular diseases. This study investigated physical activity and its relationship to risk factors for cardiovascular disease in a large population (N = 799) of civil servants from Benin City, Nigeria. METHODS: Physical activity levels were estimated by an interviewer-administered questionnaire, which determined the average hours per week over the past year spent in occupational and leisure activities. Time spent walking or biking to work was assessed as well. Other major measures included body mass index (BMI), waist-hip ratio (WHR), blood pressures, plasma insulin level, lipid profiles, and diet. RESULTS: More of the physical activity was attributed to occupational than to leisure activities. Compared with women, men had a higher activity level. No significant trend was observed across age groups. Male senior staff (a marker of higher socioeconomic status) had a lower physical activity level than male junior staff. Physical activity, especially time walking or biking to work, was inversely correlated with weight, BMI, WHR, blood pressures, insulin, total cholesterol, LDL and HDL cholesterol, and triglycerides in men, while such correlations were not consistent in women. In multivariate analysis in men, blood pressure and insulin were independently associated with BMI but not with walking, while an independent inverse association was seen between walking and BMI. CONCLUSION: Lack of physical activity was associated with adverse risk profiles for cardiovascular disease in this developing population.

Activities of Daily Living↗
PubMed2001

Behavioral risk factors for disease and preventive health practices among lesbians.

OBJECTIVES: This study compared the prevalence of health behaviors among lesbians and in the general population of women. METHODS: We used a cross-sectional community-based survey of 1010 self-identified lesbians 18 years or older. RESULTS: Compared with the general population of women, lesbians were more likely to report cigarette use, alcohol use, and heavy alcohol use. A higher percentage of lesbians were categorized as overweight, and lesbians were more likely to participate in vigorous physical activity. They were less likely to report having had a Papanicolaou test within the past 2 years but more likely to report ever having had a mammogram. CONCLUSIONS: While there may be differences in health behaviors between lesbians and the general population of women, how these differences influence the risk of subsequent disease is unknown.

Adolescent↗
PubMed2001

Women's oral health across the lifespan.

To address women's oral health conditions, it is important that oral health care providers understand basic female physiology and reproductive biology and consider the complex interaction between the environment, biology, and psychosocial development of women. Most oral health issues are not gender-specific but rather are aspects of conditions that may affect women differently. Oral health care providers should recognize that using this information to provide competent care requires knowledge, attitudes, and behaviors that are culturally and gender-sensitive. Recognizing the potential for gender-based differences in oral health and disease processes is a first step to becoming gender-competent.

Adult↗
PubMed2000

Tunable charge-density wave transport in a current-effect transistor

The collective charge-density wave (CDW) conduction is modulated by a transverse single-particle current in a transistorlike device. Nonequilibrium conditions in this geometry lead to an exponential reduction of the depinning threshold, allowing the CDWs to slide at much lower bias fields. The results are in excellent agreement with a recently proposed dynamical model in which "wrinkles" in the CDW wave fronts are "ironed" by the transverse current. The experiment might have important implications for other driven periodic media, such as moving vortex lattices or "striped phases" in high- T(c) superconductors.

Journal Article↗
PubMed2000

Life event stress and the association with spontaneous abortion in gravid women at an urban emergency department.

In this study, the authors hypothesized that life event stress is associated with an increased risk of spontaneous abortion. Using a nested case-control design in an emergency department (N = 970), stress was measured using a life event inventory and a sample drawn from R. B. Ness et al.'s (1999) Early Pregnancy Study. Gestational age at time of fetal loss served as a marker of chromosomal status. Women experiencing more than one life event used more alcohol and public assistance. Spontaneous abortion at 11 weeks or greater was associated with more life event stress (adjusted odds ratio 2.9, 95% confidence interval 1.4-6.2), whereas spontaneous abortion at any gestational age was not, implying that life event stress increases the risk of chromosomally normal spontaneous abortion. An analysis of confounders showed tobacco use was associated with an increased risk of spontaneous abortion, whereas prenatal care was only associated with fetal loss at 11 weeks or greater.

Abortion, Spontaneous↗
PubMed2000

Substance use measures among women in early pregnancy.

OBJECTIVE: Our purpose was to compare self-reported and biochemical measures for tobacco, marijuana, and cocaine exposures among women early in pregnancy. STUDY DESIGN: Women who were in the early stages of pregnancy and were examined in an inner-city emergency department were enrolled. Tobacco, marijuana, and cocaine use was measured by self-report and urinalysis. Cocaine use was also assessed by hair analysis. RESULTS: Data were available for 789 women. Among those reporting past use of tobacco, marijuana, and cocaine, 25.2%, 23.9%, and 22.7%, respectively, had positive results of urinary assays; among those reporting current use, 77.2%, 86.6%, and 75.9% had positive findings, whereas among those reporting never use 5.6%, 5. 7%, and 3.6% of results were positive. Hair analysis, in comparison with urine testing, for cocaine identified 4 times as many exposures among women who reported never using cocaine. CONCLUSIONS: Urinary assays were equally likely to be positive among women reporting never use and those reporting past use of tobacco, marijuana, or cocaine. Thus women with a positive biologic assay result were as likely to deny use of tobacco as they were to deny marijuana, or cocaine.

Cannabinoids↗
PubMed1999

Recent alcohol intake as estimated by the Health Habits and History Questionnaire, the Harvard Semiquantitative Food Frequency Questionnaire, and a more detailed alcohol intake questionnaire.

Epidemiologic studies often rely on food frequency questionnaires (FFQs) to collect information on alcoholic beverage intake. However, estimation of alcohol intake using FFQs may be of some concern because of limited questions concerning alcohol intake. The authors compared estimates of alcohol intake during the 12-24 months prior to interview obtained from the Health Habits and History Questionnaire and the Harvard Semiquantitative Food Frequency Questionnaire with those from a more extensive alcohol questionnaire, the Drinking Pattern Questionnaire, among 133 healthy subjects (75 men, 58 women) aged 35-73 years, residents of western New York State. Data were collected in 1995 during two separate interviewer-administered computer-assisted interviews conducted approximately 2 weeks apart. For each questionnaire, average daily ounces (1 oz = 30 ml) of alcohol intake from alcoholic beverages were calculated as the product of the reported beverage-specific drink size (ounces) and the average daily frequency of intake multiplied by a factor representing the percentage of alcohol provided by each beverage. Estimates of total alcohol and liquor intake, but not of beer and wine intake, tended to be higher for the Drinking Pattern Questionnaire compared with the FFQs. Spearman's correlation coefficients ranged from 0.69 to 0.84. These results suggest that although the Drinking Pattern Questionnaire produced higher estimates than either FFQ, both FFQs provide a reasonable ranking of participants' alcohol intake.

Adult↗
PubMed1999

Cocaine and tobacco use and the risk of spontaneous abortion.

BACKGROUND: Cigarette smoking and cocaine use may be risk factors for spontaneous abortion, but data supporting such a link are limited. METHODS: We studied the associations between cocaine and tobacco use and spontaneous abortion among pregnant adolescents and women (age range, 14 to 40 years) who sought care at an inner-city emergency department. A total of 400 adolescents and women had spontaneous abortions either at study entry or during follow-up (which lasted until 22 weeks' gestation), and 570 adolescents and women remained pregnant past 22 weeks' gestation. Cocaine use was measured at base line by self-reports and analysis of urine and hair samples. Cigarette smoking was measured by self-reports and urine analysis. RESULTS: The adolescents and women in both groups were predominantly black and of lower socioeconomic status. Among those who had spontaneous abortions, 28.9 percent used cocaine on the basis of hair analysis and 34.6 percent smoked on the basis of a urine cotinine assay, as compared with 20.5 percent and 21.8 percent, respectively, of the adolescents and women who did not have spontaneous abortions. The presence of cocaine in hair samples was independently associated with an increase in the occurrence of spontaneous abortion (odds ratio, 1.4; 95 percent confidence interval, 1.0 to 2.1) after adjustment for demographic and drug-use variables. However, the use of cocaine as measured by self-reports and by urine analysis was not. The presence of cotinine in urine was also independently associated with an increased risk of spontaneous abortion (odds ratio, 1.8; 95 percent confidence interval, 1.3 to 2.6). Twenty-four percent of the risk of spontaneous abortion could be related to cocaine or tobacco use. CONCLUSIONS: Cocaine and tobacco use were common in our study population and were associated with a significant risk of spontaneous abortion.

Abortion, Spontaneous↗
PubMed1999

Comparability of nutrient estimation by three food frequency questionnaires for use in epidemiological studies.

Replication of results is an important issue in studies of diet and disease, possibly dependent on data collection method. We compared assessments from the Health Habits and History Questionnaire (HHHQ), the Harvard Semiquantitative Food Frequency Questionnaire (HFFQ), and the New York State Cohort Food Frequency Questionnaire (CFFQ) for estimates of daily intakes of energy, protein, carbohydrates, total fat, dietary fiber, cholesterol, vitamins A, C, and E, and carotenoids. Fifty-nine men and 50 women aged 35-73 years completed the HHHQ and HFFQ as interviews and the 44-food CFFQ as a self-administered mailed questionnaire. Comparability was assessed with Spearman correlation coefficients. Quantitation of nutrient intake differed by nutrient, questionnaire, and nutrient calculation method. Ranking on energy and macronutrient intake for the HHHQ and HFFQ ranged from 0.62 to 0.80; ranking for micronutrient intake ranged from 0.56 to 0.80. For the CFFQ with the HHHQ or HFFQ, correlations ranged between 0.29 and 0.62. The CFFQ performs comparably to the HHHQ and HFFQ for some, but not all, nutrients; our results suggest that the HHHQ and HFFQ can be used interchangeably with reasonable confidence in studies of diet and disease.

Adult↗
PubMed1998

Cell cross-contamination in cell cultures: the silent and neglected danger.

Cell cross-contamination in cell cultures is a common problem during cell culturing and use. Contamination invalidates research results, compromises the comparison of results between laboratories, reduces reproducibility required in industrial production of cell lines, and may lead to unusable therapeutic products. The problem can be solved by increasing the awareness of its seriousness and by introducing regular quality control of cell cross-contamination in every laboratory where cells are grown and used.

Animals↗