bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of platelet-derived growth factor receptor α in breast cancer is associated with tumour progression
Authors: Carvalho Inês , Milanezi Fernanda , Martins Albino , Reis Rui M , Schmitt Fernando
Published: August 2005

Introduction

Receptor tyrosine kinases have been extensively studied owing to their frequently abnormal activation in the development and progression of human cancers. Platelet-derived growth factor receptors (PDGFRs) are receptors with intrinsic tyrosine kinase activity that regulate several functions in normal cells and are widely expressed in a variety of malignancies. After the demonstration that gastrointestinal stromal tumours without c-Kit mutations harbour PDGFR-α-activating mutations and that PDGFR-α is also a therapeutic target for imatinib mesylate, the interest for this receptor has increased considerably. Because breast cancer is one of the most frequent neoplasias in women worldwide, and only one study has reported PDGFR-α expression in breast carcinomas, the aim of this work was to investigate the potential significance of PDGFR-α expression in invasive mammary carcinomas.

Methods

We used immunohistochemistry to detect PDGFR-α overexpression on a series of 181 formalin-fixed paraffin-embedded invasive ductal breast carcinomas and in two breast cancer cell lines: MCF-7 and HS578T. We associated its expression with known prognostic factors and we also performed polymerase chain reaction–single-stranded conformational polymorphism and direct sequencing to screen for PDGFR-α mutations.

Results

PDGFR-α expression was observed in 39.2% of the breast carcinomas and showed an association with lymph node metastasis (P = 0.0079), HER-2 expression (P = 0.0265) and Bcl2 expression (P = 0.0121). A correlation was also found with the expression of platelet-derived growth factor A (PDGF-A; P = 0.0194). The two cell lines tested did not express PDGFR-α. Screening for mutations revealed alterations in the PDGFR-α gene at the following locations: 2500A→G, 2529T→A and 2472C→T in exon 18 and 1701G→A in exon 12. We also found an intronic insertion IVS17-50insA at exon 18 in all sequenced cases. None of these genetic alterations was correlated with PDGFR-α expression. The cell lines did not reveal any alterations in the PDGFR-α gene sequence.

Conclusion

PDGFR-α is expressed in invasive breast carcinomas and is associated with biological aggressiveness. The genetic alterations described were not correlated with protein expression, but other mechanisms such as gene amplification or constitutive activation of a signalling pathway inducing this receptor could still sustain PDGFR-α as a potential therapeutic target.
Tumoral and Immunologic Response After Vaccination of Melanoma Patients With an ALVAC Virus Encoding MAGE Antigens Recognized by T Cells
Authors: van Baren Nicolas , Bonnet Marie-Claude , Dréno Brigitte , Khammari Amir , Dorval Thierry , Piperno-Neumann Sophie , Liénard Danielle , Speiser Daniel , Marchand Marie , Brichard Vincent G. , Escudier Bernard , Négrier Sylvie , Dietrich Pierre-Yves , Maraninchi Dominique , Osanto Susanne , Meyer Ralf G. , Ritter Gerd , Moingeon Philippe , Tartaglia Jim , van der Bruggen Pierre , Coulie Pierre G. , Boon Thierry
Published: August 2005

Purpose

To evaluate the toxicity, antitumoral effectiveness, and immunogenicity of repeated vaccinations with ALVAC miniMAGE-1/3, a recombinant canarypox virus containing a minigene encoding antigenic peptides MAGE-3168-176and MAGE-1161-169, which are presented by HLA-A1 and B35 on tumor cells and can be recognized by cytolytic T lymphocytes (CTLs).

Materials and Methods

The vaccination schedule comprised four sequential injections of the recombinant virus, followed by three booster vaccinations with the MAGE-3168-176and MAGE-1161-169peptides. The vaccines were administered, both intradermally and subcutaneously, at 3-week intervals.

Results

Forty patients with advanced cancer were treated, including 37 melanoma patients. The vaccines were generally well tolerated with moderate adverse events, consisting mainly of transient inflammatory reactions at the virus injection sites. Among the 30 melanoma patients assessable for tumor response, a partial response was observed in one patient, and disease stabilization in two others. The remaining patients had progressive disease. Among the patients with stable or progressive disease, five showed evidence of tumor regression. A CTL response against the MAGE-3 vaccine antigen was detected in three of four patients with tumor regression, and in only one of 11 patients without regression.

Conclusion

Repeated vaccination with ALVAC miniMAGE-1/3 is associated with tumor regression and with a detectable CTL response in a minority of melanoma patients. There is a significant correlation between tumor regression and CTL response. The contribution of vaccine-induced CTL in the tumor regression process is discussed in view of the immunologic events that could be analyzed in detail in one patient.
Erythrocyte Zinc Protoporphyrin Is Elevated With Prematurity and Fetal Hypoxemia
Authors: Lott David G. , Zimmerman M. Bridget , Labbé Robert F. , Kling Pamela J. , Widness John A.
Published: August 2005

Objective. To examine the utility of red blood cell (RBC) zinc protoporphyrin/heme ratio (ZnPP/H) as an indicator of fetal iron status, because unfavorable neurodevelopmental outcomes have been associated with poor iron status at birth, as indicated by low serum ferritin, and because few reliable indicators of fetal and early neonatal iron status exist.

Methods. Consecutively studied preterm and term fetuses at delivery included the following groups: (1) control nonhypoxic, (2) fetuses with intrauterine growth retardation (IUGR), and (3) fetuses of insulin-treated mothers (FDM). We hypothesized (1) that rapid growth velocity associated with an accelerated erythropoiesis among normal fetuses will lead to reduced iron delivery to a rapidly expanding RBC mass and higher umbilical cord blood RBC ZnPP/H and (2) that fetuses that are exposed to pathologic hypoxemia will experience an additional increase in erythropoiesis and higher cord ZnPP/H. ZnPP/H was determined on saline-washed cord blood erythrocytes by hematofluorometry and was examined for its relationship with clinical factors and cord blood laboratory measurements indicative of tissue oxygenation (plasma erythropoietin [EPO] and reticulocyte count) and iron status (plasma ferritin and erythrocyte indices). Statistical testing included 1-way analysis of variance, 2-way analysis of variance with covariates, simple linear regression, and multiple regression analysis.

Results. Among control group subjects, gestational age at birth was inversely correlated with RBC ZnPP/H and reticulocyte count and positively correlated with ferritin and EPO. Relative to control subjects, IUGR and FDM fetuses at specified gestational age groupings had higher ZnPP/H, lower plasma ferritin, and higher plasma EPO. Statistical modeling of the relationship between ZnPP/H and plasma ferritin among all study groups demonstrated significant impacts of gestational age, plasma EPO, maternal hypertension, and maternal smoking.

Conclusions. The inverse association of fetal ZnPP/H with gestational age at birth among control subjects is attributable to erythropoietic stimulation likely as a result of increasing growth velocity at the earliest gestational ages. The relatively higher ZnPP/H observed among fetuses in the IUGR and FDM groups likely is attributable to increased erythropoietic activity secondary to pathologic hypoxemia. Decreased placental iron transfer may also have limited iron availability and contributed to elevated ZnPP/H in the IUGR group. These data support the concept that increased erythropoietic activity and/or limited iron transport may place infants of diabetic mothers and infants with growth retardation at risk for developing systemic iron deficiency later in infancy and in early childhood.
Randomized, Controlled Trial of Dexamethasone in Neonatal Chronic Lung Disease: 13- to 17-Year Follow-up Study: II. Respiratory Status, Growth, and Blood Pressure
Authors: Jones Rosamond A. K. ,   on behalf of the Collaborative Dexamethasone Trial Follow-up Group
Published: August 2005

Objectives. To study the growth, health status, and respiratory outcomes at 13 to 17 years of infants enrolled in a double-blind, randomized, controlled trial of dexamethasone for the treatment of neonatal chronic lung disease.

Participants. A total of 287 infants who were chronically dependent on supplementary oxygen between 2 and 12 weeks of age were recruited from 31 centers in 6 countries to a double-blind, randomized, controlled trial of dexamethasone base (0.5 mg/kg per day for 1 week) or placebo, and survivors were evaluated at 3 years. Children from the 25 British and Irish centers were traced for reassessment at 13 to 17 years of age.

Outcome Measures. Respiratory symptoms, lung-function testing, height, weight, head circumference, blood pressure, health resource usage, and school absences.

Results. There was no significant difference in respiratory outcomes between the dexamethasone and placebo groups. Lung function was impaired but with no difference between the 2 groups. Growth was also impaired in both groups, with height z score of −0.7, weight z score of −0.4, and head circumference z score of −1.1. Systolic blood pressure was >95th percentile for age and height for 15% of children, but with no difference between the 2 groups. There was no difference in the numbers of hospital admissions for respiratory causes or other causes.

Conclusions. Despite a shorter duration of neonatal assisted ventilation, there is no evidence that dexamethasone use is associated with long-term improvement in lung function. Impaired growth and poor health status are long-term consequences of neonatal chronic lung disease, irrespective of exposure to neonatal dexamethasone.
Childhood Obesity and Type 2 Diabetes Mellitus
Authors: Hannon Tamara S. , Rao Goutham , Arslanian Silva A.
Published: August 2005

Until recently, the majority of cases of diabetes mellitus among children and adolescents were immune-mediated type 1a diabetes. Obesity has led to a dramatic increase in the incidence of type 2 diabetes (T2DM) among children and adolescents over the past 2 decades. Obesity is strongly associated with insulin resistance, which, when coupled with relative insulin deficiency, leads to the development of overt T2DM. Children and adolescents with T2DM may experience the microvascular and macrovascular complications of this disease at younger ages than individuals who develop diabetes in adulthood, including atherosclerotic cardiovascular disease, stroke, myocardial infarction, and sudden death; renal insufficiency and chronic renal failure; limb-threatening neuropathy and vasculopathy; and retinopathy leading to blindness. Health care professionals are advised to perform the appropriate screening in children at risk for T2DM, diagnose the condition as early as possible, and provide rigorous management of the disease.
Early Respiratory Infections, Asthma, and Allergy: 10-Year Follow-up of the Oslo Birth Cohort
Authors: Nafstad Per , Brunekreef Bert , Skrondal Anders , Nystad Wenche
Published: August 2005

Objective. It has been hypothesized that early infections protect against the development of atopic disease, but there have been few long-term follow-up studies. We estimated the associations between early respiratory infections and doctor-diagnosed asthma, allergic rhinitis, and skin-prick sensitization in children at 10 years of age in the Oslo Birth Cohort, established in 1992–1993. We also considered birth order and attendance at a child care center as proxy measures of increased exposure to infections early in life.

Methods. A total of 2540 children were followed from birth to the age of 10 years. Experiences of respiratory infections were recorded in follow-up surveys at 6 and 12 months. At age 10, questions were asked about current symptoms of asthma and allergic rhinitis and about having ever received a doctor diagnosis for these diseases. A subsample (n = 1740) of the cohort was tested for skin-prick test reactivity.

Results. Current asthma was related to lower respiratory tract infection (adjusted odds ratio [OR]: 2.1; 95% confidence interval: 1.3–3.0) and croup (adjusted OR: 2.3; 95% confidence interval: 1.3–4.2) in the first year. ORs for allergic rhinitis and skin-prick sensitization were smaller but mainly positive. Birth order and child care attendance at age 1 year were not significantly associated with any of the studied outcomes.

Conclusions. Early respiratory infections did not protect against the development of asthma, allergic rhinitis, or sensitization to common allergens during the first 10 years of life but increased the risk for asthma symptoms at age 10 in this population.
Poor Predictive Validity of the Bayley Scales of Infant Development for Cognitive Function of Extremely Low Birth Weight Children at School Age
Authors: Hack Maureen , Taylor H. Gerry , Drotar Dennis , Schluchter Mark , Cartar Lydia , Wilson-Costello Deanne , Klein Nancy , Friedman Harriet , Mercuri-Minich Nori , Morrow Mary
Published: August 2005

Objective. The Bayley Scales of Infant Development, Second Edition (BSID II) are commonly used to assess outcomes of extremely low birth weight (ELBW) infants. We sought to assess the predictive validity of the BSID II Mental Developmental Index (MDI) for cognitive function at school age.

Design/Methods. Of 330 ELBW infants admitted in 1992–1995, 238 (72%) survived to the age of 8 years, of whom 200 (84%) were tested at both 20 months’ corrected age (CA) and 8 years. Mean birth weight was 811 g, mean gestational age was 26.4 weeks, 41% were boys, and 60% were black. Measures included the BSID II at 20 months’ CA and the Kaufman Assessment Battery for Children (KABC) Mental Processing Composite (MPC) at 8 years’ postnatal age. BSID II MDI and MPC scores were compared and the predictive validity calculated for all 200 ELBW children and for the 154 ELBW neurosensory-intact subgroup. Predictors of stability or change in cognitive scores were examined via logistic regression adjusting for gender and sociodemographic status.

Results. For all ELBW children, the mean MDI was 75.6 ± 16 versus a mean KABC of 87.8 ± 19. For the neurosensory-intact subgroup, the mean MDI was 79.3 ± 16 and the mean KABC was 92.3 ± 15. Rates of cognitive impairment, defined as an MDI or KABC of <70, dropped from 39% at 20 months’ CA to 16% at 8 years for the total ELBW population and from 29% to 7% for the neurosensory-intact subgroup. The positive predictive value of having an MPC of <70 given an MDI of <70 was 0.37 (95% confidence interval [CI]: 0.27, 0.49) for all ELBW infants, 0.20 (95% CI: 0.10, 0.35) for the neurosensory-intact subgroup, and 0.61 (95% CI: 0.42, 0.77) for the neurosensory-impaired subgroup. The negative predictive values were 0.98, 0.99, and 0.85 for the 3 groups, respectively. Neurosensory impairment at 20 months’ CA predicted lack of improvement of cognitive function (odds ratio: 6.9; 95% CI: 2.4, 20.2). Children whose cognitive scores improved between 20 months and 8 years had significantly better school performance than those whose scores stayed at <70, but they did less well than those whose scores were persistently >70.

Conclusions. The predictive validity of a subnormal MDI for cognitive function at school age is poor but better for ELBW children who have neurosensory impairments. We are concerned that decisions to provide intensive care for ELBW infants in the delivery room might be biased by reported high rates of cognitive impairments based on the use and presumptive validity of the BSID II MDI.
Dating Violence and Sexually Transmitted Disease/HIV Testing and Diagnosis Among Adolescent Females
Authors: Decker Michele R. , Silverman Jay G. , Raj Anita
Published: August 2005

Objective.Previous studies demonstrate significant associations between dating-violence victimization and sexual risk behaviors among adolescent girls; however, a relationship between dating violence and actual sexually transmitted disease (STD)/HIV testing and diagnosis has yet to be investigated among a representative sample. The present study assesses associations between dating violence and STD/HIV testing and diagnosis among a representative sample of sexually active adolescent girls.

Methods.Data from 9th- to 12th-grade female students completing the 1999 and 2001 Massachusetts Youth Risk Behavior Surveys and reporting having ever had sexual intercourse (N = 1641) were examined. Odds ratios for STD/HIV testing and diagnosis that were based on experiences of dating violence and adjusted for STD/HIV risk behaviors and demographics were calculated.

Results.More than one third (38.8%) of adolescent girls tested for STD or HIV and more than half (51.6%) of girls diagnosed with STD/HIV reported experiencing dating violence. Compared with nonabused girls, girls who experienced both physical and sexual dating violence were 3.0 times more likely to have been tested for STD and HIV, and 2.6 times more likely to report an STD diagnosis.

Conclusions.After adjusting for STD/HIV risk behaviors, dating violence remains significantly associated with STD/HIV testing and diagnosis among sexually active adolescent girls.
Novel RAG1 Mutation in a Case of Severe Combined Immunodeficiency
Authors: Zhang Junyan , Quintal Linda , Atkinson Adelle , Williams Brent , Grunebaum Eyal , Roifman Chaim M.
Published: August 2005

Objective. The recombination activating enzymes RAG1 and RAG2 are essential to the process of V(D)J rearrangement in B and T cells and thus to the development of normal immune function. Mutations in RAG1 or RAG2 can lead to a spectrum of disorders, ranging from typical B−T− severe combined immunodeficiency to Omenn's syndrome. We present a unique presentation of RAG1 deficiency.

Patient. We report on a 6-month-old girl who presented with severe respiratory distress, which continued to progress despite antibiotic therapy but seemed to respond to treatment with corticosteroids. The patient exhibited no erythroderma or eosinophilia, and her lymphoid organs were not enlarged.

Results. Investigation of the immune system showed normal numbers of CD3+ T cells, which expressed either CD4 or CD8. Subsequent analysis of the T-cell receptor demonstrated that nearly all CD3+ T cells were clonal; one clone expressed CD4, whereas the other expressed CD8. The extremely restricted T-cell repertoire and the lack of circulating B cells prompted analysis of the RAG1 gene, which revealed a novel homozygous thymine to cytosine substitution at nucleotide position 2686.

Conclusions. This case underscores the importance of more extensive evaluation of the immune system even when widely available, standard, flow cytometric analysis shows normal numbers of T cells that express CD4 or CD8, especially in the absence of circulating B cells.
The Effect of rhg1 on Reproduction of Heterodera glycines in the Field and Greenhouse and Associated Effects on Agronomic Traits
Authors: Brucker Eric , Niblack Terry , Kopisch-Obuch Friedrich J. , Diers Brian W.
Published: August 2005

The soybean cyst nematode (SCN) (Heterodera glycines Ichinohe) continues to be the most damaging soybean pest [Glycine max (L.) Merr.] in the USA. A major gene that provides partial resistance to SCN is rhg1, which is located on linkage group (LG) G. The objectives of this study were to test the effect of rhg1 on SCN reproduction in both the field and greenhouse and on agronomic traits in the field. Two populations of near isogenic lines (NILs) that segregated for rhg1 were developed to test the effect of the gene. These NIL populations were tested for their ability to support SCN cyst development in a thermo‐regulated water bath in a greenhouse and egg production estimated from soil samples taken from each plot in field tests. The NIL populations were evaluated for agronomic traits in field plots to determine the associated effects of rhg1 on these traits. In the greenhouse, NILs predicted to be carrying the resistance allele for rhg1 on the basis of a linked marker supported significantly (P < 0.01) fewer cysts than NILs carrying the susceptibility allele. In field tests, the final egg population density (Pf) was significantly lower and there was a smaller reproductive rate (Rf) in NILs carrying the resistance allele at rhg1 than susceptible NILs for both populations across and within environments in 2003. In only one population did the resistant NILs out‐yield the susceptible NILs, and this occurred only when the initial SCN pressure was high [>500 SCN eggs (100 cm3 soil)−1]. These results show that resistance at rhg1 can have a large effect on SCN reproduction and may result in a significant yield increase.
Genotype and Environment Affect Rhizome Growth of Birdsfoot Trefoil
Authors: Beuselinck P. R. , Brummer E. C. , Viands D. K. , Asay K. H. , Smith R. R. , Steiner J. J. , Brauer D. K.
Published: August 2005

Rhizome production has been transferred from wild germplasm of Lotus corniculatus L. (broadleafed birdsfoot trefoil) into domesticated germplasm to produce ‘ARS‐2620’ and ‘ARS‐2424’ (a L. corniculatus × L. uliginosus hybrid). The objective of this study was to determine if field environments in the United States differing in latitude affect rhizome expression in genotypes of ARS‐2620 and ARS‐2424. Ramets of rhizomatous genotypes of ARS‐2620 and ARS‐2424, and nonrhizomatous ‘Norcen’ were planted at seven locations in late July and August 1999. At five locations in 2000 and 2001, dormant plants were hand‐dug in late autumn or winter. Traits measured were mean crown‐plus‐root mass, crown circumference, and percentage survival for all entries, and rhizome mass for the two rhizomatous entries. Significant (P ≤ 0.001) location × genotype effects were observed for all traits in 2000, but only for percentage survival in 2001. In 2001, the effect of locations was significant for all traits (P ≤ 0.001), but genotype effects were significant (P ≤ 0.001) only for crown circumference and percentage survival. The rhizomatous entries were larger in circumference and had a greater crown‐plus‐root mass than Norcen. Rhizomes appeared to be beneficial to plant survival and plant growth, but rhizomes did not assure performance or survival, as we did not identify a genotype that performed well across locations. High plant mortality and extensive tissue necrosis caused by root and crown‐rot complex reduced overall plant performance and rhizome expression and masked the interpretive value of the data from the five locations. Plants grown in Logan, UT, were notable for their large size and rhizome production relative to the other locations, and as having advantageous, but undefined, environmental conditions beneficial to the performance of rhizomatous birdsfoot trefoil.
Dry Matter Accumulation Predictors for Optimal Yield in Soybean
Authors: Board James E. , Modali Harikrishna
Published: August 2005

Identification of predictors for soybean [Glycine max (L.) Merr.] optimal yield (4500 kg ha−1 for Louisiana growing conditions) would help farmers identify profitability and aid in determination of environmental factors limiting crop yield. Since environmental influences on yield act mainly through effects on total dry matter (TDM) accumulation during the emergence to R5 period (R5 = start of seed filling), TDM at R1 (first flowering) and TDM at R5 are promising predictors for optimal yield. Thus, the main objective of this study was to determine if TDM(R1) and TDM(R5) can be used as predictors for optimal yield. A secondary objective was to analyze relationships between yield components, TDM, and yield to explain why certain TDM levels can serve as predictors for optimal yield. Data for this study were collected from previous studies containing a variety of cultural treatments (planting dates, row spacings, plant populations, and waterlogging stress) conducted near Baton Rouge, LA (30° N Lat) between 1987 to 1996 and combined to make a single data set. The data represent a wide range of yield, yield component, and TDM values across which regression analyses were conducted to achieve our objectives. The study indicated that 200 g m−2 and 600 g m−2 at R1 and R5, respectively, were valid predictors for optimal yield. Environmental effects on yield were regulated by node and reproductive node number per area, pod number per area, and seed number per area. These yield components responded to TDM at R1 and R5 in a fashion similar to that shown for yield, thus supporting the use of TDM at R1 and R5 as predictors for optimal yield.
Planting Configuration × Cultivar Effects on Soybean Production in Low‐Yield Environments
Authors: Heitholt J. J. , Farr J. B. , Eason R.
Published: August 2005

Texas soybean [Glycine max (L.) Merr.] growers generally use row spacings ranging from 15 to 102 cm and seeding rates that provide 25 to 62 plants m−2 However, the interaction of cultivars with planting configuration is not well understood. The objectives of this research were to measure the yield response of selected cultivars to seeding population and row spacing in low‐yielding environments and to relate morphology to this response. In north Texas, on a highly calcareous clay soil with 10 maturity group (MG) III cultivars (where 2‐yr average yield was 1.22 Mg ha−1) and three seeding populations (25–75 m−2), only one cultivar, AG3702, showed consistent yield increases at 50 and 75 m−2 The row‐spacing tests were conducted in two north Texas environments where 14 MG IV cultivars varying in leaf size were grown in 36‐ vs. 71‐cm rows and two environments in southeast Texas where 21 cultivars varying in height and maturity (MG IV– MG VIII) were grown (18‐ vs. 76‐cm rows). In north Texas, yields were not significantly different between 71‐cm rows (1.31 Mg ha−1) and 36‐cm rows (1.02 Mg ha−1). Likewise, in southeast Texas, yield in 18‐cm rows (1.49 Mg ha−1) was similar to yield in 76‐cm rows (1.46 Mg ha−1). Cultivar × row spacing effects on yield were not significant and leaf size and plant height did not affect the yield response to row spacing. In general, our results demonstrated that management × genotype interactions within the range of these cultivars and management practices were not important in these low‐yielding environments and possibly were overwhelmed by the severity and timing of drought stress.
Total Dietary Fiber Variability in a Cross Section of Crotalaria juncea Genetic Resources
Authors: Morris J. B. , Kays S. E.
Published: August 2005

Sunn hemp seeds contain several phytochemicals including fiber with potential phytopharmaceutical use. A study of 15 sunn hemp, Crotalaria juncea L., accessions demonstrated that total dietary fiber and protein content are significantly variable. As dietary fiber increases in the sunn hemp seed, protein decreases. Differences in total dietary fiber suggest that sufficient variability exists in this trait to allow enhancement in sunn hemp cultivars through plant breeding.
Development of an Asymbiotic Reference Line for Pea cv. Bohatýr by De Novo Mutagenesis
Authors: Novák Karel , Šlajs Martin , Biedermannová Eva , Vondrys Josef
Published: August 2005

Comparison of asymbiotic and symbiotic pairs of lines (difference technique) is a reliable and accessible method for determining the contribution of symbiotic nitrogen fixation to the yield of legume crops. To obtain an isogenic reference line for a commercial pea (Pisum sativum L.) a mutagenesis program was initiated with cv. Bohatýr. Ethyl methanesulfonate (EMS) treatment of large seeds was optimized in a closed system to scale‐up the process and to improve safety. The 18‐h exposure of non‐presoaked seeds to 0.15% (w/w) EMS solution resulted in 30% field emergence in the M1 generation and in 1.04% of chlorophyll mutants and 3.64% of mutants classified as symbiotic in the M2 However, only 48.4% of the growth chamber‐detected and 21.6% of the field‐detected presumable symbiotic mutants were found to be stable genetic deviations in the M3 to M5 Twenty‐two preliminary characterized stable mutants comprised one nonnodulating, one with reduced nodulation, one with markedly delayed nodulation, and 19 lines with affected nodule development and function. Further evaluation under controlled conditions and in field trials identified the nonfixing line Budfix2 as a suitable reference line for field estimates of symbiotic nitrogen fixation. This line was shown to be physiologically equivalent to the original cultivar when grown under asymbiotic conditions, i.e., when the symbiotic fault was compensated for by exogenous mineral nitrogen. The availability of Budfix2 allows for direct application of the difference method in the particular pea cultivar Bohatýr, as well as in further varieties after trait introgression. The additional symbiotic mutants generated in the course of the search for a reference line are expected to enhance the variability available for the genetic dissection of rhizobial nodulation.
A QTL Analysis of White Clover Seed Production
Authors: Barrett B. A. , Baird I. J. , Woodfield D. R.
Published: August 2005

White clover (Trifolium repens L.) exhibits complex inheritance of seed production potential. Genome maps allow plant breeders to dissect the genetic control of complex traits into discreet factors with Mendelian inheritance, each of which is called a quantitative trait locus (QTL). A pair‐cross between two highly heterozygous white clover genotypes created an F1 mapping population (n = 182) used to investigate the genetic control of seed yield (SY) and three component traits: inflorescence density (ID), yield per inflorescence (YI), and thousand‐seed weight (TSW). Analysis of 3 yr of field data from a replicated trial in the primary seed production region of New Zealand indicated no strong correlations among the component traits. The ANOVA indicated significant genotype, year, and genotype × year effects for SY, ID, and YI; and genotype and genotype × year effects for TSW. Using genotype data for 209 microsatellite loci in the allotetraploid genome, the multiple QTL model analysis resulted in the discovery of 23 QTLs related to seed production in white clover. Both parent plants harbored beneficial alleles for SY and the three component traits. A region of the genome at the distal end of linkage group D2 was implicated in a number of traits related to seed production, and was strongly implicated in the control of YI and SY. The central region of linkage group C2 was strongly implicated in the control of ID and SY. Parent trait values were similar for ID, yet the population was highly variable for this trait and segregated for multiple QTLs, indicating the utility of this experimental design for QTL discovery in crosses among heterozygous individuals with similar phenotypes. Most QTLs were dominant, suggesting suitability for marker‐assisted selection (MAS) in white clover.
Phospholipid Acyl Chain and Phospholipase Dynamics during Cold Acclimation of Winter Wheat
Authors: Skinner D. Z. , Bellinger B. S. , Halls S. , Baek K.-H. , Garland-Campbell K. , Siems W. F.
Published: August 2005

Phospholipid (PL) composition is known to change in plants exposed to cold temperature. The dynamics of PL acyl chain pairs and genes encoding phospholipase enzymes were studied in winter wheat (Triticum aestivum L.) during cold acclimation. Mass spectrometry was used to characterize PL dynamics, and quantitative real‐time PCR was used to characterize phospholipase gene mRNA transcript dynamics during cold acclimation. The proportion of PLs with mismatched acyl chains decreased concomitantly with an increase in total PLs during the first week of cold exposure. Proportions of mismatched acyl chains then increased, while total PLs varied little. Numbers of mRNA transcripts of phospholipase (PL)D, PLC, and PLA2 increased in response to cold and remained at elevated levels throughout a 4‐wk period. Lysophosphatidylcholine (LPC) increased as much as 14‐fold over the 5‐wk period and increased significantly less in a less cold tolerant cultivar than more tolerant cultivars. It appeared that newly synthesized PLs with equal‐length acyl chains form a part of the initial response to cold temperature; they are then modified to contain near‐initial levels of mismatched acyl chains during acclimation. LPC is a highly active signal molecule and PLA2, PLC, and PLD are involved in generation of phospholipid‐based signaling molecules; hence, it appeared PL signaling is involved in initial and continuing responses to cold temperature.
Biotype 2 Russian Wheat Aphid Resistance among Wheat Germplasm Accessions
Authors: Collins Meghan B. , Haley Scott D. , Peairs Frank B. , Rudolph Jeffrey B.
Published: August 2005

The Russian wheat aphid [Diuraphis noxia (Mordvilko), RWA] is an important pest of wheat (Triticum aestivum L.) in the western Great Plains region of the United States. The recent identification of a RWA biotype (provisionally denoted as Biotype 2) that is virulent on currently deployed RWA‐resistant cultivars necessitates the rapid identification of resistance to the new biotype. The objective of this study was to identify Biotype 2 RWA resistance among a collection of germplasm accessions previously determined to be resistant to the original North American biotype of RWA (provisionally denoted as Biotype 1). A collection of 761 germplasm accessions was evaluated in standard seedling screening tests with Biotype 2 RWA. ‘TAM 107’ (carries no RWA resistance genes) and ‘Halt’ (Dn4 resistance gene) were used as susceptible checks while the germplasm line 94M370 (Dn7 resistance gene) was used as a resistant check. Evaluation of accessions showing at least a moderate level of resistance in unreplicated tests was repeated with three replications in a randomized complete block design. Forty‐four germplasm accessions were identified as having high to moderate levels of resistance to Biotype 2 RWA. Most of these accessions originated from areas of the world where RWA is endemic or were derived from germplasm accessions that originated from these areas. Ten accessions showed a level of resistance comparable with the 94M370 check. These accessions should prove useful in future genetic studies and for breeding for resistance to Biotype 2 RWA.
Urinary iodine excretion from the 125i-ria laboratory personnel in inep
Authors: Nedic Olgica , Stojanovic Dimitrije , Savin-Zegarac Svetlana , Cvejic Dubravka
Published: August 2005

The aim of this study was to examine urinary iodine excretion from the 125I-RIA-INEP laboratory personnel. Radiodosimetric measurements have shown that people received ionization energy doses that were significantly bellow the permissible levels, i.e. 0.15 - 0.45 mSv. The amount of iodide in urine varied from 123 to 396 mg/L (1.0 - 3.2 mmol/L) and the mean value was 264 mg/L (2.1 mmol/L; n = 25, SD = 75.3 mg/L or 0.60 mmol/L, CV = 28.5 %). On the basis of the obtained data it can be concluded that professionaly exposed individuals in the examined laboratory consume sufficient amount of dietary iodine, thus minimizing a risk of internal accumulation of 125I.
Effects of prolonged atherogenic diet on lipid status and some antioxidant parameters in rat blood
Authors: Velkovski Sasko , Milosevic Verica , Ristic Snezana , Pavlovic Sladjan , Saicic Zorica , Starcevic Vesna
Published: August 2005

In this study we measured the effects of eight-week atherogenic diet on plasma lipid status, glutathione- S-transferase activity, red blood cells-catalase activity, and glutathione and vitamin E plasma level adult male Wistar albino rats. The animals were sacrificed by decapitation 24 h after the end of the diet. Triglycerides, total cholesterol, and LDL cholesterol plasma levels, as well as LDL/HDL ratio, and vitamin E plasma level significantly raised (p<0,05) after the diet in comparison with the controls. HDL cholesterol plasma level glutathione- -S-transferase and red blood cells-catalase activities, and glutathione plasma level remained unchanged (p>0,05). These findings demonstrated that prolonged specific atherogenic diet in rats induced significant raise of the lipid parameters, but did not affect blood antioxidant status.
The role of evidence-based laboratory medicine in health service
Authors: Majkic-Singh Nada
Published: August 2005

Evidence-based laboratory medicine (EBLM) is the use of the current best evidence of the utility of laboratory tests in making decisions about the care of individual patients. This practice means integrating laboratory and clinical experience with the last available external evidence from systematic research. It means that the definition of EBLM focuses on two key elements: experience and evidence from systematic research. Although the term evidence-based medicine (EBM) was created in Canada at Mc Master University by a group lad by Dr Gard Guyatt, there are various claims as to the origin of its practice. Regardless of its origins, many factors have come together over the past 30 years to drive the movement to EBM. One factor is those individual physicians, faced with numerous medical informations; the second factor is the global phenomenon of increasing health care costs and third is that patients who have generally more education, want the best in diagnostics and therapies. It means that evidence-based medicine has been driven by the need to cape with information overload, by costcontrol, and by public impatient for the best in diagnostics and treatment. Clinical guidelines care maps, and outcome measures are quality improvement tools for the appropriateness, efficiency and effectiveness of health services. Laboratory professionals must direct more effort to demonstrating the impact of laboratory tests on a greater variety of clinical outcomes. Evidence-based laboratory medicine aims to advise clinical diagnosis and management of disease through systematic researching and disseminating generalisible new knowledge that meets the standard of critical review on clinically effective practice of laboratory investigations. In laboratory medicine, the use of tests increases; new tests are constantly introduced, but "old" tests are seldom removed from the repertoire. This, together with limited public funds for the health care should underline the challenge for laboratory professionals to provide evidence for the utility of different tests. This practice means integrating laboratory and clinical experience with the best available external evidence from systematic research therefore, it is important that advice given by laboratory medicine professionals are sound and based on evidence in the pre-analytical, analytical, and post-analytical phases of the diagnostic process. This paper provides an insight into the rationale, methodology and the phases of the EBLM.
Rapid characterization of b-thalassemia mutations by reverse dot blot and allele-specific pcr analysis
Authors: Pavlovic Sonja , Urosevic Jelena , Djureinovic Tatjana , Janic Dragana , Krivokapic-Dokmanovic Lidija
Published: August 2005

This paper reports a case of b-thalassaemia major whose molecular diagnosis was achieved by using modern methods of molecular genetics. This example demonstrates the strategy we chose to detect b-thalassaemia mutations in the Republic of Serbia in order to complete molecular screening in our population and to make prenatal diagnosis in pregnancies at risk. The analysis of genomic DNA isolated from the blood of patient affected with thalassaemia major is carried out by the methods: RDB (reverse dot blot) and ARMS (amplification refractory mutation system). It is shown that the patient is a compound heterozygote for two b- -thalassaemic mutations: b+IVSI-110 and b+IVSI-6.
Hypothalamo-pituitary-adrenocortical and sympatho-adrenomedullar systems in stress response
Authors: Cvijic Gordana , Djordjevic Jelena
Published: August 2005

The hypothalamic-pituitary-adrenocortical and sympatho-adrenomedullar systems are major effectors systems that serve to maintain homeostasis during exposure to various stressors. The neurochemical pathways controlling activation of hypothalamic-pituitary-adrenocortical and sympatho-adrenomedullar systems are of special interest. Catecholamines present in specific brain areas as well as in peripheral tissues are responsible for adequate stress response regulating the relationships between the hypothalamic-pituitary-adrenocortical and sympatho-adrenomedullar functions. In last decade, numerous studies have demonstrated differential sympathoneural and adrenomedullary responses during exposure to different stressors. Some stressors provoke the strongest reaction of adrenocortical activity than that of adrenomedularry, while others do the opposite. Each type of stressor has its own central neurochemical and peripheral neuroendocrine "signature" with quantitative and qualitative distinct mechanisms.
Characteristics of the pituitary immunopositive ACTH cells in rat females after chronic exposure to constant light
Authors: Milosevic Verica , Nestorovic Natasa , Negic Natasa , Filipovic Branko , Brkic Branislava , Starcevic Vesna
Published: August 2005

The effects of chronic exposure to light of adult female Wistar rats on growth and function of pituitary adrenocorticotropes (ACTH cells) were examined. The animals were exposed to continuous light of 600 lux for 95 days, starting on day 30 of age. Control rats were kept under a 12:12 h light-dark cycle, at ambient temperature. ACTH-producing cells were studied using the peroxidase-antiperoxidase immunohistochemical procedure and blood samples were collected for hormone analyses. In animals exposed to a chronic light-treatment all morphometric parameters measured throughout the present study i.e.: ACTH cell volume, nuclear volume and relative volume density were increased by 22% and the differences between this group and the controls were statistically significant (p<0.05). The concentration of plasma ACTH was elevated by 13% in light-exposed group in comparison with the control and this difference was statistically significant (p<0.05), as well. These findings suggest that continuous exposure to light is specifically involved in growth and secretory activity of ACTH cells of adenohypophysis of rat females.
Hemostatic parameters as hypercoagulability indicators in pregnancy
Authors: Vodnik Tatjana , Ignjatovic Svetlana , Majkic-Singh Nada
Published: August 2005

The concentrations of plasma proteins involved in the process of coagulation are changed during the normal pregnancy, interfering with balance between procoagulant and anticoagulant systems. These changes include the increased activity of coagulation factors, the increased fibrin production and suppression of fibrinolysis. In this way, the risk of blood loss is reduced by physiological mechanisms, but the risk of thrombosis becomes higher. Thrombosis of placental blood vessels gives rise to placental insufficiency causing the repeated miscarriages, retardation of fetal growth, eclampsia intrauterine death of fetus and pre-term delivery. The causes of these incidents are the changes occurring within protein C coagulation system. The central anticoagulant enzyme is APC, which inactivates the activated factors V and VIII by proteolysis and, in that manner, inhibits the production of thrombin. The resistance to APC is the impairment of blood coagulation characterized by lower sensitivity to anticoagulant activity of APC. This disorder is in 95% of cases, caused by specific factor V gene point mutation and designated as F V Leiden. It is point mutation on locus 1691 where guanin is replaced by adenine what will lead to synthesis of modified F V molecule in which arginine is replaced by glutamine on locus 506. Arginine 506 is the locus of factor Xa binding, and it inhibits the inactivation of factor Va by the action of APC. The testing performed in pregnant women with regular and complicated pregnancy, in different periods, has shown that fibrinogen, fibrin monomer, TAT complex and PAI were good markers of hipercoagulability in pregnancy. The values of protein C activity were within normal limits. Protein S values were below lower limits. Global activity of protein C-anticoagulant pathway and its relation with procoagulant system were presented by quantitative measurement using Pro C Global test, while determination of activated protein C by means of APC sensitivity test was used for identification of persons with APC resistance e.g. with higher risk of thrombosis. Significantly lower PC-NR and APC-NR values were found in pregnant women with repeated miscarriages and in pregnant women with hypertension in relation to pregnant women with regular pregnancy. The results revealed significantly lower APC-anticoagulant activity in pregnancy, particularly in pregnancy associated with complications. Diagnostic accuracy of these parameters as markers of thrombotic changes in pregnancy was tested by ROC analysis. PC-NR and APC-NR showed satisfactory diagnostic accuracy as markers of thrombotic changes in pregnant women, more precisely, they were found to be good indicators of resistance to activated protein C in pregnancy.
Homocysteine: Chemistry, metabolism and roles in pathophysiology processes
Authors: Mirkovic Dusko , Majkic-Singh Nada , Ignjatovic Svetlana
Published: August 2005

In 1962, 30 years after chemical structure discovery of homocysteine, Carson and Neil reported work in which they described cases of two young people with severe mental retardation and high homocysteinuria. In 1975 McCully emphasized the association between homocysteinuria and thrombus-occlusive vascular changes. Period 1991-98, is the time of very extensive comparative studies, with aim of establishing links between premature coronary artery disease and high homocysteine level in plasma. These results in a whole show that biochemical findings of a mild increase of homocysteine plasma levels in span of 15-45 mmol/L, are independent risk factor for premature coronary artery disease appearance. So far mechanism of direct homociysteine uninfluenced on endothelial vascular vessels cells, or influence of any other factor, which play role in methionine-homocysteine-cysteine path (vitamins B6, B12, folic acid) are not strictly elucidated.
Mannose binding lectin in sera and synovial fluids of patients with rheumatoid arthritis
Authors: Mijuskovic Zoran , Colic Miodrag , Zgradic Ivan , Rackov Ljiljana , Radunovic Goran , Pilipovic Nada , Nikolajevic Radmila , Stojanovic Jelica
Published: August 2005

It has been supposed that low levels of mannose binding lectin (MBL) may be involved in protection of rheumatoid arthritis associated with agalactosil forms of GOIgG immunoglobilins found in rheumatoid synovial fluid and lead to enhanced complement activation and joint cartilage damages. In order to examine the possible link between MBL and mediated complement activation its concentration was measured in sera and synovial fluids of 59 patients classified in moderate and severe activity RA groups and compared with the levels in the same biological fluids of the control group with menisci lesions. No patients had undetectable or lowered MBL in both RA groups. Mean values were either normal or elevated depending on the severity of the disease as a response to inflammation. This finding does not exclude a possible role of MBL-GOIgG mediated complement activation, but provides no support to mitigating RA severity.