bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are amniotic fluid C-reactive protein and glucose levels, and white blood cell counts at the time of genetic amniocentesis related with preterm delivery?
Authors: Tarım Ebru , Bağış Tayfun , Kılıçdağ Esra Bulgan , Sezgin Nurzen , Yanık Filiz 
Published: December 2005

Abstract

Objective: To compare women with spontaneous preterm delivery before 37 weeks and women who delivered at term with respect to amniotic fluid C-reactive protein (CRP), glucose levels, and white blood cell counts at the time of genetic amniocentesis.

Study design: The study was conducted on 216 pregnant women who underwent genetic amniocentesis between the 15th and 18th weeks of gestation at Baskent University Obstetrics and Gynecology Department. All patients were followed until delivery for the occurrence of pregnancy complication. Indications for amniocentesis included abnormal triple test results showing increased risk for Down's syndrome, advanced maternal age and sonographic findings indicative for chromosomal abnormalities. The samples were carried immediately to the laboratory for cytogenetic and biochemical examination. Women with spontaneous preterm delivery before 37 weeks (n=20) and those who delivered at term (n=196) were compared with respect to some maternal and infant characteristics, amniotic fluid C-reactive protein, glucose levels, and amniotic fluid white blood cell counts.

Results: During the study period 244 patients underwent amniocentesis. A chromosomal abnormality was present in 11 patients. 1 patient had a spontaneous pregnancy loss within 3 weeks after the procedure and 16 patients were delivered for fetal or maternal indications (preeclampsia, fetal growth restriction, placenta previa). The remaining 216 women were included in the study and investigated for the risk of preterm delivery. The prevalence of spontaneous preterm delivery before 37 weeks was 9.3% (20/216). There were no significant differences between the preterm delivery and the term delivery groups with respect to C-reactive protein levels and white blood cell counts. Mean amniotic glucose levels were significantly lower in the preterm delivery group (P<0.05). Amniotic fluid glucose levels of ≤46 mg/dL had a sensitivity of 100% and NPV of 100%.

Conclusion: Amniotic fluid glucose levels at the time of genetic amniocentesis are lower in women with spontaneous preterm delivery before 37 weeks compared to those who delivered at term. Amniotic fluid glucose levels of ≤46 mg/dL at the time of genetic amniocentesis may be more sensitive, cheaper and have higher negative predictive value than C-reactive protein levels and white blood cell counts for the prediction of patients in spontaneous preterm labor. The greatest benefit of amniotic fluid glucose testing might be when the physician judges the patient to be at low risk for preterm delivery.
Characterization of the humoral immune response to glutamic acid decarboxylase in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and/or type 1 diabetes
Authors: Ronkainen Matti S , Härkönen Taina , Perheentupa Jaakko , Knip Mikael 
Published: December 2005

Objective: A humoral autoimmune response to glutamic acid decarboxylase (GAD65) is common both in patients with type 1 diabetes and in those with the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, while overt type 1 diabetes is relatively rarely diagnosed in APECED patients. The aim of this study was to assess whether this difference in the incidence of type 1 diabetes is associated with variability in the humoral immune response to GAD65, one of the major autoantigens in type 1 diabetes.
Methods: Epitope- and isotype-specific GAD65 autoantibodies were analysed in 20 patients with APECED and 20 patients with newly diagnosed type 1 diabetes alone by radiobinding assays.
Results: GAD65 autoantibodies targeted the middle and carboxy-terminal regions of GAD65 and occasionally the amino-terminal region in the APECED patients and comprised mainly the IgG1 subclass and less frequently the IgG2 and IgG4 subclasses. The profile of epitope- and isotype-specific GAD65 autoantibodies was similar in type 1 diabetes and APECED, except that IgG2 subclass antibodies were observed more often and at higher levels in the patients with type 1 diabetes alone (P < 0.05). None of the measured parameters separated APECED patients with type 1 diabetes from those without type 1 diabetes.
Conclusion: APECED-associated humoral autoimmunity to GAD65 does not differ markedly from that observed in type 1 diabetes; only IgG2-GAD65 antibodies may be more closely associated with the latter entity.
Functional analysis of the I.3, I.6, pII and I.4 promoters of CYP19 (aromatase) gene in human osteoblasts and their role in vitamin D and dexamethasone stimulation
Authors: Enjuanes Anna , Garcia-Giralt Natalia , Supervía August , Nogués Xavier , Ruiz-Gaspà Silvia , Bustamante Mariona , Mellibovsky Leonardo , Grinberg Daniel , Balcells Susana , Díez-Pérez Adolfo 
Published: December 2005

Objective: Current evidence suggests that extragonadal estrogens play an important role in bone metabolism. Estrogen biosynthesis is catalyzed by P450aromatase, encoded by the CYP19 gene. The aims of this paper were to study CYP19 gene expression in human osteoblasts under several hormone and cytokine treatments and to define promoter regions involved in this regulation.
Methods: CYP19 transcript levels were measured from primary human osteoblasts and MG-63 cells by real-time PCR in basal conditions, and in response to seven different hormones and cytokines. Four promoters of CYP19 gene were cloned upstream of the luciferase gene and transfected into MG-63 cells. The effect of vitamin D and dexamethasone in these promoter activities was evaluated.
Results: Vitamin D and dexamethasone were potent stimulators of CYP19 transcription, while testosterone and 17β-estradiol stimulated moderately. Promoter pII proved the most potent in driving transient luciferase expression. Promoter I.4 displayed moderate activity, while promoters I.3 and I.6 were weak. A region upstream of exon I.3, including exon I.6, was identified as containing repressor elements of promoter pII. Promoter I.3 activity was modulated by repressors located within exon I.3, while an enhancer of promoter I.4 was detected within exon I.4. In the absence of fetal calf serum, dexamethasone stimulation was observed on promoters I.3 and I.4, while vitamin D stimulation acted only on promoter I.3.
Conclusions: Four regulatory regions of promoters pII, I.3 and I.4 are relevant to CYP19 expression in human osteoblasts. Vitamin D and dexamethasone modulate transcription through these regions.
Sex-specific association of PTPN22 1858T with type 1 diabetes but not with Hashimoto’s thyroiditis or Addison’s disease in the German population
Authors: Kahles Heinrich , Ramos-Lopez Elizabeth , Lange Britta , Zwermann Oliver , Reincke Martin , Badenhoop Klaus 
Published: December 2005

Background: Endocrine autoimmune disorders share genetic susceptibility loci, causing a disordered T-cell activation and homeostasis (HLA class II genes, CTLA-4). Recent studies showed a genetic variation within the PTPN22 gene to be an additional risk factor.
Materials and Methods: Patients with type 1 diabetes (n = 220), Hashimoto’s thyroiditis (n = 94), Addison’s disease (n = 121) and healthy controls (n = 239) were genotyped for the gene polymorphism PTPN22 1858 C/T.
Results: Our study confirms a significant association between allelic variation of the PTPN22 1858 C/T polymorphism and type 1 diabetes mellitus (T1D). 1858T was observed more frequently in T1D patients (19.3% vs 11.3%, P = 0.0009; odds ratio for allele T = 1.88, 95% confidence interval [1.3–2.7]). Furthermore, we found a strong association in female patients with T1D (P = 0.0003), whereas there was no significant difference between male patients with type 1 diabetes and male controls. No significant difference was observed between the distribution of PTPN22 C/T in patients with Hashimoto’s thyroiditis or Addison’s disease and healthy controls.
Conclusion: The PTPN22 polymorphism 1858 C/T may be involved in the pathogenesis of type 1 diabetes mellitus by a sex-specific mechanism that contributes to susceptibility in females.
GH responsiveness varies during the menstrual cycle
Authors: Gleeson Helena K , Shalet Stephen M 
Published: December 2005

Objective: The GH–IGF-1 axis is affected by oestrogen. Both endogenous and exogenous oestrogen facilitates the central drive of pulsatile GH secretion. However, the effect on IGF-1 levels is more subtle, and a reduction in GH sensitivity has been proposed. The IGF generation test has confirmed reduced GH sensitivity with high doses of exogenous oestrogen. It is not known, however, whether fluctuant levels of endogenous oestrogen modify GH sensitivity. To investigate this further, women were challenged with the IGF-1 generation test at different stages of the menstrual cycle.
Methods: Nine women (age 38(6) years (mean (s.d.)) with regular menstrual cycles were recruited. An IGF-1 generation test, s.c. injection of 7 mg GH, was performed in the early-follicular (EF), periovulatory (PO) and midluteal (ML) phases. IGF-1, insulin-like growth factor binding protein (IGFBP)-3 and acid-labile subunit (ALS) levels were measured at baseline and 24 h after GH administration.
Results: Oestradiol levels were lower in the EF than PO or ML phases (32.6(7.8) vs 69.6(16.2) vs 66.6(23.6) pg/ml respectively (repeated measures ANOVA, P < 0.001)). Baseline IGF-1 was lower, but increment IGF-1 (peak minus baseline) was higher in the EF than PO or ML phases (baseline: 291.8(56.6) vs 335.0(55.2) vs 346.6(78.2) ng/ml (P = 0.008); increment IGF-1: 234.6(59.2) vs 194.7(37.8) vs 185.2(37.3) ng/ml (P = 0.008)).
Conclusions: Increased endogenous oestrogen levels are associated with only a modestly elevated baseline IGF-1 from midcycle onward despite a previously reported twofold increase in GH secretion. In parallel with this apparent GH insensitivity, increased endogenous oestrogen levels are associated with reduction in GH sensitivity evidenced by reduction in increment IGF-1. This may have clinical implications for women with isolated GH deficiency with regular menstrual cycles on a fixed dose of GH. This possibility requires further study.
Lithium stimulates proliferation in cultured thyrocytes by activating Wnt/β-catenin signalling
Authors: Rao A S , Kremenevskaja N , Resch J , Brabant G 
Published: December 2005

Background: Lithium, clinically used in the treatment of bipolar disorders, is well known to induce thyroid growth. However, the mechanism involved is only incompletely characterized. Although it is conventionally believed that thyroid proliferation depends on the thyroid-stimulating hormone (TSH)/cAMP/cAMP response element binding protein (CREB) pathway, recent data indicate that Wnt/β-catenin signalling may be of critical importance. In other cell types lithium activates canonical Wnt signalling by GSK-3β inhibition, which in turn stabilizes cytosolic free β-catenin. Here we investigated the potential modulation of Wnt/β-catenin signalling under lithium treatment in primary and neoplastic human thyrocytes.
Methods: Primary (S18) and neoplastic (NPA, FTC133) thyrocytes treated with and without LiCl were analysed using Western blotting, immunoprecipitation, reporter-gene assay, MTT proliferation assay and transfection studies.
Results: LiCl dose-dependently inhibited GSK-3β, stabilized free β-catenin and inhibited β-catenin degradation. Furthermore, LiCl altered the assembly of adherens junction by upregulating the E-cad-herin repressor, Snail, and downregulated E-cadherin expression. At a dose of 5 mM, LiCl significantly increased the proliferative potency of thyrocytes, which appeared to be mediated by β-catenin, since nuclear β-catenin stimulated T-cell factor/lymphoid enhancer factor (TCF/LEF)-mediated transcription and upregulated downstream targets like cyclin D1. To characterize the specificity of Wnt/β-catenin-driven thyrocyte proliferation, we transfected primary thyrocytes and FTC133 cells with dominant negative TCF4 to block Wnt-dependent pathways or with dominant negative CREB to inhibit the TSH/cAMP cascade. In cells transfected with dominant negative CREB lithium-stimulated proliferation was unchanged whereas blocking Wnt/β-catenin by dominant negative TCF4 reduced proliferation by approx. 50%.
Conclusion: Our data indicate that Wnt/β-catenin signalling is of major importance in the control of lithium-dependent thyrocyte proliferation.
Analysis of the interaction between human steroid 21-hydroxylase and various monoclonal antibodies using comparative structural modelling
Authors: Miguel Ricardo Núñez , Chen Shu , Nikfarjam Laleh , Kominami Shiro , Carpenter Byron , Dal Pra Chiara , Betterle Corrado , Zanchetta Renato , Nakamatsu Takashi , Powell Michael , Hewer Rachel , Blundell Tom L , Smith Bernard Rees , Furmaniak Jadwiga 
Published: December 2005

Objective: To study the interaction between human steroid 21-hydroxylase (21-OH) and monoclonal antibodies (MAbs) to 21-OH directed to 3 different epitopes recognised by 21-OH autoantibodies characteristic of autoimmune Addison’s disease.
Design: Build comparative structural models of 21-OH, 21-OH MAbs and complexes of 21-OH–21-OH MAbs and study the effects of 21-OH MAbs on 21-OH enzyme activity. Then, analyse the relationship between sites important for binding of 21-OH MAbs and 21-OH autoantibodies and sites important for 21-OH enzyme activity.
Methods: Variable (V) regions of 21-OH MAbs (M21-OH1, M21-OH3, M21-OH5) were sequenced and models of the MAbs built using structures of antibodies in the database as templates. A comparative model of 21-OH was built using the crystal structure of rabbit cytochrome p450 2c5/3LVdH as template. 21-OH enzyme activity was measured in terms of conversion of [3H]progesterone to deoxycorticosterone and the effect of purified MAb IgGs on 21-OH enzyme activity was assessed.
Results: M21-OH1, M21-OH3 and control MAb had no effect on 21-OH enzyme activity with 88.8% ± 24% (n = 6), 86.7% ± 7.6% (n = 6) and 86.5% ± 10.6% (n = 6) of activity remaining in the presence of the respective IgGs. This was consistent with the epitopes for M21-OH1 and M21-OH3 being located distant from 21-OH enzyme active sites in our 21-OH model. The epitope for M21-OH5 which inhibited 21-OH enzyme activity (48.5 ± 8.3% activity remaining; P < 0.001 compared with control MAb IgG) was found close to the redox protein binding site in our 21-OH model.
Conclusions: A comparative model of 21-OH has been produced. Analysis of experimental data in the context of the model suggests that M21-OH5 inhibits 21-OH enzyme activity through interference with redox protein binding.
Plasma calcitonin gene-related peptide is increased prior to obesity, and sensory nerve desensitization by capsaicin improves oral glucose tolerance in obese Zucker rats
Authors: Gram Dorte X , Hansen Anker J , Wilken Michael , Elm Torben , Svendsen Ove , Carr Richard D , Ahrén Bo , Brand Christian L 
Published: December 2005

Objective: It has earlier been demonstrated that capsaicin-induced desensitization improves insulin sensitivity in normal rats. However, whether increased capsaicin-sensitive nerve activity precedes the onset of insulin resistance in diet-induced obesity – and therefore might be involved in the pathophysiology – is not known. Further, it is of relevance to investigate whether capsaicin desensitization improves glycaemic control even in obese individuals and we therefore chose the obese Zucker rats to test this.
Design and methods: Plasma levels of calcitonin gene-related peptide (CGRP; a marker of sensory nerve activity) was assessed in 8-week-old Zucker rats. To investigate whether capsaicin desensitization (100 mg/kg at 9 weeks of age) would also ameliorate glycaemia in this non-diabetic model, we assessed oral glucose tolerance at 7 weeks after capsaicin.
Results: It was found that plasma CGRP levels were elevated in obese Zucker rats prior to the onset of obesity (16.1±3.4 pmol/l in pre-obese Zucker rats vs 6.9±1.1 pmol/l in lean littermates; P = 0.015) despite similar body weights. Furthermore, capsaicin desensitization reduced both fasting blood glucose (4.3±0.2 mmol/l vs 5.1±0.2 mmol/l in controls; P = 0.050) as well as the mean blood glucose level during an oral glucose tolerance test (OGTT) (6.8±0.3 mmol/l vs 8.6±0.5 mmol/l in control obese rats; P = 0.024) whereas the plasma insulin levels during the OGTT were unchanged. However this did not lead to an improvement in insulin resistance or to a reduction of tissue triglyceride accumulation in muscle or liver.
Conclusion: We concluded that capsaicin-induced sensory nerve desensitization improves glucose tolerance in Zucker rats. Since, in this study, plasma CGRP levels, a marker of sensory nerve activity, were increased in the pre-obese rats, our data support the hypothesis that increased activity of sensory nerves precedes the development of obesity and insulin resistance in Zucker rats.
Could cortisol explain the association between birth weight and cardiovascular disease in later life? A meta-analysis
Authors: van Montfoort N , Finken M J J , le Cessie S , Dekker F W , Wit J M 
Published: December 2005

Objective: Studies about the association between birth weight and circulating cortisol level have been published from 1998 onwards. However, their findings were inconsistent. To quantitatively assess the overall association between birth weight and circulating cortisol level, we aimed to perform a meta-analysis of the published literature.
Methods: A literature search was conducted in PubMed, and selected papers were systematically reviewed. A pooled regression coefficient was calculated for the entire group as well as for males and females separately.
Results: Data from 11 study populations were pooled (n = 2301). These populations differed with respect to geographical area, age, sex distribution, inclusion criteria and gestational age. We found a statistically significant inverse association between birth weight and circulating cortisol level: a 1 kg lower birth weight was associated with a 25.3 nmol/l (95% confidence interval (CI): 5.9–44.8) higher cortisol level. Separate results were reported for males and females in six study populations. The association in males was 20.6 nmol/l per kg (95% CI: 4.2–37.0) and in females it was 30.9 nmol/l per kg (95% CI: 7.4–54.4).
Conclusion: Differences between study populations hampered the comparability of the included studies. Although the majority of studies were underpowered, by using a meta-analytic approach we found an inverse association between birth weight and circulating cortisol level. Thus, our findings suggest that there is some evidence for a possible role of the hypothalamus–pituitary–adrenal axis in the epidemiological association between birth weight and cardiovascular disease. However, the strength of the overall association between birth weight and circulating cortisol level was weak.
Dynamics of Early Childhood Overweight
Authors: Salsberry Pamela J. , Reagan Patricia B. 
Published: December 2005

Objective. To study the dynamic processes that drive development of childhood overweight by examining the effects of prenatal characteristics and early-life feeding (breastfeeding versus bottle feeding) on weight states through age 7 years. We test a model to determine whether prenatal characteristics and early-life feeding influence the development of a persistent early tendency toward overweight and/or whether prenatal characteristics and early-life feeding factors influence the likelihood that children will change weight states as they get older.Methods. Data from the National Longitudinal Survey of Youth’s Child-Mother file were used to implement these analyses. A total of 3022 children were included in this sample. For inclusion in this sample, valid information on height and weight during 3 consecutive interviews when the child was aged 24 to 95 months as well as valid data on prenatal and birth characteristics were needed. The primary outcome measure was childhood overweight (BMI &gt;95th percentile). Multivariate logistic models and first-order Markov models were estimated.Results. Early development of childhood overweight was associated with race, ethnicity, maternal prepregnancy obesity, maternal smoking during pregnancy, and later birth years. In later years, the factor that contributed the most to being overweight was having been overweight in the previous observation period. However, with conditioning on the child’s having been overweight in the previous observation period, the prenatal factors that contributed to early childhood overweight, except for birth cohort, were also associated with development of overweight among children who had previously been normal weight and perpetuated the persistence of overweight over time.Conclusions. This research suggests that prenatal characteristics, particularly race, ethnicity, maternal smoking during pregnancy, and maternal prepregnancy obesity, exert influence on the child’s weight states through an early tendency toward overweight, which then is perpetuated as the child ages. These findings are intriguing as they provide additional clues to the genesis of childhood overweight and suggest that overweight prevention may need to begin before pregnancy and in early childhood.
Project 27/28: Inquiry Into Quality of Neonatal Care and Its Effect on the Survival of Infants Who Were Born at 27 and 28 Weeks in England, Wales, and Northern Ireland
Authors: Acolet Dominique , Elbourne Diana , McIntosh Neil , Weindling Michael , Korkodilos Marilena , Haviland Jo , Modder Jo , Macintosh Mary ,   on behalf of the Confidential Enquiry Into Maternal and Child Health
Published: December 2005

Objective. To identify variations in standards of neonatal care in the first week of life that might have contributed to deaths in infants who were born at 27 and 28 weeks' gestation.
Methods. A case-control study was conducted of infants who were born at 27 and 28 weeks' gestation in England, Wales, and Northern Ireland during a 2-year period. Cases were neonatal deaths; control subjects were randomly selected survivors at day 28. Main outcome measures were failures of prespecified standards of care or deficiencies in care reported by regional panels assessing anonymized medical records.
Results. Failures of standards of care relating to ventilatory support (adjusted odds ratio [OR]: 3.29; 95% confidence interval [CI]: 1.97–5.49), cardiovascular support (OR: 2.37; 95% CI :1.36–4.13), and thermal care (OR: 1.71; 95% CI: 1.21–2.43) were associated with neonatal death. Frequencies of unmet resuscitation standards (range: 3%–46%) and of delays in surfactant administration (range: 38%–40%) were similar in cases and control subjects. Panels identified significantly more deficiencies in all aspects of neonatal care in cases with the exception of the management of infection. Stratification by clinical condition of infants at birth showed a stronger association between overall standard of care and death when infants were in a good condition at birth.
Conclusions. Our findings suggest an association between quality of neonatal care and neonatal deaths, most marked for early thermal care and ventilatory and cardiovascular support. Poor overall quality of care was more strongly associated with deaths when the infant was in a good condition at birth.