bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal diagnosis of factor X deficiency using a combination of direct mutation detection and linkage analysis with an intragenic single nucleotide polymorphism
Authors: Camire Rodney , Ann Denchy Ruth , Day George A. , Lanzano Patricia , Sheth Sujit , Brown Stephen 
Published: June 2003

AbstractObjectiveTo present a family in which it was possible to perform prenatal diagnosis for recessively inherited factor X deficiency using both direct mutation detection as well as linkage analysis.MethodsIn a family where both parents were known to be carriers of factor X deficiency, fetal DNA was obtained from an ongoing pregnancy by CVS in the first trimester. Direct DNA sequencing was used to detect a previously identified factor X mutation, and linkage analysis using a single nucleotide polymorphism (SNP) was used to follow the segregation of the other parent's factor X alleles.ResultsOur studies predicted the fetus in question to be a heterozygote carrier of factor X deficiency, and this was demonstrated to be correct at birth.ConclusionsThis is the first reported case of prenatal diagnosis of factor X deficiency. In addition, this case demonstrates the remarkable utility of SNPs in linkage analysis of rare genetic disorders. Copyright © 2003 John Wiley & Sons, Ltd.
Cystic fibrosis: selecting the prenatal screening strategy of choice
Authors: Wald N. J. , Morris J. K. , Rodeck C. H. , Haddow J. E. , Palomaki G. E. 
Published: June 2003

AbstractCystic fibrosis is a serious disorder. Research into the treatment of affected individuals is in progress, but a cure is not expected in the near future. In this review, we demonstrate that prenatal screening for cystic fibrosis meets the requirements for a worthwhile screening programme. We explain the reasons that have led us to conclude that one approach (‘couple screening’) is the method of choice. The couple‐based approach calls for reporting results to the couple as a unit. Only if both parents are found to be carriers is the result designated screen‐positive and an amniocentesis or chorionic villus sampling offered. This offers a substantial reduction in the proportion of women with unaffected pregnancies with positive results (the false‐positive rate) compared with other methods without reducing the detection of affected pregnancies. It also avoids creating a screen‐positive group for which no definitive diagnosis is available. This is a problem with other screening methods. The couple method can achieve a 72% detection rate for a 0.1% false‐positive rate. The screening method is simple, non‐invasive, reliable, safe and reasonably cost effective. Existing programmes have shown that screening using this method is acceptable to health care professionals and patients. Setting up a national prenatal screening programme for cystic fibrosis is timely and should be implemented using the couple screening method. Copyright © 2003 John Wiley & Sons, Ltd.
Absence of fetal nasal bone and aneuploidies at first‐trimester nuchal translucency screening in unselected pregnancies
Authors: Zoppi Maria Angelica , Ibba Rosa Maria , Axiana Carolina , Floris Marcella , Manca Fabiola , Monni Giovanni 
Published: June 2003

AbstractObjectivesThe absence of nasal bone (NB) has been noted in trisomy 21 fetuses at first‐trimester ultrasound, in high‐risk pregnancies. In this study, the nasal bone was evaluated in relation to fetal karyotype, in unselected pregnancies.MethodsFrom September 2001 to September 2002, the fetal facial profile was examined at the 11 to 14 weeks' scan for screening by nuchal translucency (NT). Risks for trisomy 21 were calculated using the Fetal Medicine Foundation's software, and the presence or absence of NB was noted. Prenatal karyotype and pregnancy outcomes were recorded.ResultsNT screening was performed in 5532 fetuses from 5425 pregnancies (85 twins, 8 triplets, 2 quadruplets). The visualization of fetal profile was obtained in 5525 fetuses (99.8%), and in 5491 fetuses (99.4%) the NB was present and in 34 cases (0.6%) it was absent. Fetal karyotype and pregnancy outcome were available in 3503 pregnancies, and 40 chromosomal abnormalities were diagnosed (27 trisomies 21, 5 trisomies 18, 2 trisomies 13, 3 Turner syndromes, 1 partial trisomy 9 and 2 others). The NB was absent in 19 (70%) trisomies 21, 4 trisomies 18 (80%), 2 Turner syndromes (66%), in the partial trisomy 9, in 7 normal karyotype fetuses (0.2%), and in a case with spontaneous first‐trimester abortion before prenatal diagnosis. A significant difference was found between NT thickness, expressed as a multiple of the median, in trisomy 21 fetuses with present and absent nasal bone.ConclusionsThe absence of NB at 11 to 14 weeks is more frequent in fetuses with trisomy 21 and other aneuploidies than in normal karyotype fetuses. Copyright © 2003 John Wiley & Sons, Ltd.
Prenatal diagnosis of congenital rubella infection in the second trimester of pregnancy
Authors: Tang Julian W. , Aarons Emma , Hesketh Louise M. , Strobel S. , Schalasta Gunnar , Jauniaux Eric , Brink Nicola S. , Enders Gisela 
Published: June 2003

AbstractObjectivesThis case report describes the clinical presentation, diagnosis and management of a case of acute rubella infection in the second trimester. The complex issues of prenatal diagnosis of a congenital rubella infection are discussed.MethodsA 30‐year‐old woman presented with a fine macular rash at 15 weeks' gestation. Laboratory testing included maternal rubella‐specific IgG and IgM detection (booking blood and acute‐phase sample) together with measurement of IgG avidity. Prenatal diagnosis at 19 weeks (amniocentesis) and 23 weeks (amniocentesis and fetal blood) was done using a reverse‐transcriptase polymerase chain reaction to detect rubella‐specific RNA. The fetal blood sample was also tested for rubella‐specific IgM.ResultsMaternal serological results confirmed an acute rubella infection at 15 weeks' gestation. Rubella‐specific RNA and IgM were detected in the fetal blood taken at 23 weeks' gestation. However, no rubella RNA was detected in either of the amniotic fluid samples collected at 19 and 23 weeks.ConclusionIn second‐trimester rubella where risk of fetal damage is low, prenatal diagnosis can identify the rubella‐infected fetus, allowing the parents to make a more informed decision about their options. The optimal sample for prenatal diagnosis is fetal blood as no rubella‐specific RNA was detected in the amniotic fluid. Copyright © 2003 John Wiley & Sons, Ltd.
Visualization of AS paths on the Internet
Authors: Kimura Takumi 
Published: June 2003

AbstractContent distribution via Internet applications such as the World Wide Web or streaming applications has become very common. The quality of such content distribution greatly depends on the performance of the distribution paths which are constructed from one or more autonomous systems (ASs). We focus on understanding the content distribution path topology, by which a content service provider (CSP) can improve the content distribution quality in a network environment using one or more ASs. This paper proposes a measurement and visualization procedure for the content distribution path topology in terms of ASs. We show that this procedure is scalable for various numbers of destination users, and that it converges faster than previous methods. © 2003 Wiley Periodicals, Inc. Syst Comp Jpn, 34(9): 20–26, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10426
Advancing systems engineering for systems‐of‐systems challenges
Authors: Chen Pin , Clothier Jennie 
Published: June 2003

AbstractEngineering activities in future organization development, including various information‐based systems, vary, but all result in evolutions of an organization, its capabilities and systems. These evolutions occur in a context of Systems‐of‐Systems (SoS) where the organization must maintain a sustained, sustainable, and controlled SoS evolution as a whole. This paper presents an understanding of SoS challenges to the application of Systems Engineering (SE) in organizational evolutionary development and discusses the difference between “developing a SoS” and “developing systems in a SoS context” from an SE management perspective. A new approach to SE process organization and management is presented in order to help an organization cope with the high complexity of SoS evolutions and improve its architecture practice. Philosophically different from many SoS SE studies that consider mainly how to develop a SoS, the new approach is to add a dimension or components of SE practice at the organization level that is aimed at creating a better engineering environment to enable effective applications of traditional SE practice in implementing SoS evolutions. © 2003 Wiley Periodicals, Inc. Syst Eng 6: 170–183, 2003
Organizational architectures and mission requirements: A model to determine congruence
Authors: Handley Holly A. H. , Levis Alexander H. 
Published: June 2003

AbstractIn order to determine congruence between proposed organizational architectures and evolving mission requirements, an executable model was developed in support of a subject experiment testing the hypothesis that an organization congruent with an expected mission results in better performance than a noncongruent organization. The model is based on the task process, the sequence of stages that occur in order to complete a task, where the delays of each stage are based on the interactions of the task with decision‐makers and resources; in this case, tasks are limited to simple tasks completed by a single decision‐maker with a single resource. The model is configured to a particular organizational design and simulated with a scenario, a list of tasks and their parameters that characterize the mission. Congruence is determined by using regression analysis to fit a linear equation to the output of the simulation and computing the coefficient of determination to evaluate the fit. The model was developed with trial experiment data and validated with post‐experimental results. This model provides the foundation for a future, second order model that will include multiple decision‐makers interacting with multiple resources to complete complex tasks. © 2003 Wiley Periodicals, Inc. Sys Eng 6: 184–194, 2003
Cognitive functioning in patients with a small infarct in the brainstem
Authors: Van Zandvoort Martine , De Haan Edward , Van Gijn Jan , Jaap Kappelle Laurens 
Published: June 2003

AbstractEarlier findings in patients with a small supratentorial white matter infarct demonstrated subtle impairments of cognition. This is in line with reported difficulties in regaining premorbid level of functioning in daily life activities, even though any physical neurological deficits are no longer present. Either a “bystander effect” of adjoining gray matter or a long distance effect through hypometabolism or other neurochemical changes might underlie these impairments. To find the best explanation, a group of 17 patients with a lacunar infarct in the brainstem was neuropsychologically evaluated and compared with a closely matched control group. The patients demonstrated significantly impaired task performance on a constellation of neuropsychological tasks that was very similar to the findings previously found in patients with a supratentorial lacunar infarct (Boston Naming Test, TEA visual elevator, category fluency, Trailmaking Test). We conclude that a small white-matter infarct may affect cognitive functioning in a nonspecific way independently of its location. (JINS, 2003, 9, 490–494.)
A differential response to nortriptyline and fluoxetine in melancholic depression: the importance of age and gender
Authors: Joyce P. R. , Mulder R. T. , Luty S. E. , McKenzie J. M. , Rae A. M. 
Published: June 2003

Objective: To consider the impact of age and gender on the antidepressant response to nortriptyline and fluoxetine in melancholic depression.Method: Of 191 depressed patients, 113 met study criteria for melancholia. All patients were randomized to receive either fluoxetine or nortriptyline. Response rates, defined as an improvement of 60% or more on the Montgomery Asberg Depression Rating Scale over 6 weeks of antidepressant treatment on an intention to treat basis, were examined by age, and by age and gender.Results: Melancholic depressed patients 40 years or older, especially men, had a markedly superior response to nortriptyline compared with fluoxetine. Conversely, melancholic depressed patients, age18–24 years, especially women, had a markedly superior response to fluoxetine.Conclusion: Age and gender appear to be critical variables in understanding differential antidepressant responses to tricyclic antidepressants and selective serotonin reuptake inhibitors in melancholic depression.
Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid‐type CB2 receptor
Authors: Klegeris Andis , Bissonnette Christopher J , McGeer Patrick L 
Published: June 2003

Two cannabinoid receptors, CB1 and CB2, have been identified. The CB1 receptor is preferentially expressed in brain, and the CB2 receptor in cells of leukocyte lineage. We identified the mRNA for the CB1 receptor in human neuroblastoma SH‐SY5Y cells, and the mRNA and protein for the CB2 receptor in human microglia and THP‐1 cells.
Δ9‐and Δ8‐tetrahydrocannabinol (THC) were toxic when added directly to SH‐SY5Y neuroblastoma cells. The toxicity of Δ9‐ THC was inhibited by the CB1 receptor antagonist SR141716A but not by the CB2 receptor antagonist SR144528. The endogenous ligand anandamide was also toxic, and this toxicity was enhanced by inhibitors of its enzymatic hydrolysis.
The selective CB2 receptor ligands JWH‐015 and indomethacin morpholinylamide (BML‐190), when added to THP‐1 cells before stimulation with lipopolysaccharide (LPS) and IFN‐γ, reduced the toxicity of their culture supernatants to SH‐SY5Y cells. JWH‐015 was more effective against neurotoxicity of human microglia than THP‐1 cells. The antineurotoxic activity of JWH‐015 was blocked by the selective CB2 receptor antagonist SR144528, but not by the CB1 receptor antagonist SR141716A. This activity of JWH‐015 was synergistic with that of the 5‐lipoxygenase (5‐LOX) inhibitor REV 5901.
Cannabinoids inhibited secretion of IL‐1β and tumor necrosis factor‐α (TNF‐α) by stimulated THP‐1 cells, but these effects could not be directly correlated with their antineurotoxic activity.
Specific CB2 receptor ligands could be useful anti‐inflammatory agents, while avoiding the neurotoxic and psychoactive effects of CB1 receptor ligands such as Δ9‐THC.

British Journal of Pharmacology (2003) 139, 775–786. doi:10.1038/sj.bjp.0705304
Endocannabinoids protect the rat isolated heart against ischaemia
Authors: Lépicier Philippe , Bouchard Jean‐François , Lagneux Caroline , Lamontagne Daniel 
Published: June 2003

The purpose of this study was to determine whether endocannabinoids can protect the heart against ischaemia and reperfusion.
Rat isolated hearts were exposed to low‐flow ischaemia (0.5–0.6 ml min−1) and reperfusion. Functional recovery as well as CK and LDH overflow into the coronary effluent were monitored. Infarct size was determined at the end of the experiments. Phosphorylation levels of p38, ERK1/2, and JNK/SAPK kinases were measured by Western blots.
None of the untreated hearts recovered from ischaemia during the reperfusion period. Perfusion with either 300 nM palmitoylethanolamide (PEA) or 300 nM 2‐arachidonoylglycerol (2‐AG), but not anandamide (up to 1 μM), 15 min before and throughout the ischaemic period, improved myocardial recovery and decreased the levels of coronary CK and LDH. PEA and 2‐AG also reduced infarct size.
The CB2‐receptor antagonist, SR144528, blocked completely the cardioprotective effect of both PEA and 2‐AG, whereas the CB1‐receptor antagonist, SR141716A, blocked partially the effect of 2‐AG only. In contrast, both ACEA and JWH015, two selective agonists for CB1‐ and CB2‐ receptors, respectively, reduced infarct size at a concentration of 50 nM.
PEA enhanced the phosphorylation level of p38 MAP kinase during ischaemia. PEA perfusion doubled the baseline phosphorylation level of ERK1/2, and enhanced its increase upon reperfusion. The cardioprotective effect of PEA was completely blocked by the p38 MAP kinase inhibitor, SB203580, and significantly reduced by the ERK1/2 inhibitor, PD98059, and the PKC inhibitor, chelerythrine.
In conclusion, endocannabinoids exert a strong cardioprotective effect in a rat model of ischaemia–reperfusion that is mediated mainly through CB2‐receptors, and involves p38, ERK1/2, as well as PKC activation.

British Journal of Pharmacology (2003) 139, 805–815. doi:10.1038/sj.bjp.0705313
Two novel mutations in the gene encoding thyroxine‐binding globulin (TBG) as a cause of complete TBG deficiency in Taiwan
Authors: Su Ching‐Chieh , Wu Yi‐Chi , Chiu Chih‐Yang , Won Justin Ging‐Shing , Jap Tjin‐Shing 
Published: June 2003

Summaryobjective Thyroxine‐binding globulin (TBG) encoded by the TBG gene on chromosome Xq22 is the major transport protein, carrying approximately 75% of circulating T4. Inherited defects in TBG are associated with three phenotypes based on the level of TBG in serum of affected hemizygous males: complete TBG deficiency (TBG‐CD), partial TBG deficiency (TBG‐PD) and TBG excess (TBG‐E). In this study, we report two unrelated Han Chinese males with complete TBG deficiency who carry different mutations in the TBG gene.patients Two index cases of Han males who were diagnosed as having TBG deficiency on the basis of undetectable serum TBG and an additional 75 (50 males and 25 females) normal Han Chinese.measurement Serum thyroid hormones were measured by chemiluminescent immunoassay, thyroid autoantibodies by an agglutination test, and TSH receptor antibody and TBG by radioimmunoassay. Genomic DNA extraction, polymerase chain reaction (PCR) and DNA sequence analysis of the TBG gene were performed with standard methods.results One index case had one missense mutation in his copy of the gene, a G → A transition in codon 52 that results in the replacement of serine by asparagine, and a known polymorphism in codon 283 (TTG → TTt) that results in the replacement of leucine by phenylalanine. The allelic frequency of TBG‐Poly allele in 75 normal Han Chinese (100 chromosomes) was 31%. A second index case was hemizygous for a nonsense mutation in codon 280 of exon 3 (TGG → TGa). This mutation, located in the C‐terminal of TBG, predicts a markedly truncated protein.conclusions This is the first report of complete thyroxine‐binding globulin deficiency (TBG‐CDT1 and TBG‐CDT2) due to TBG gene mutations in Taiwan.
Effects of low‐iodide diet on postsurgical radioiodide ablation therapy in patients with differentiated thyroid carcinoma
Authors: Pluijmen Maurice J. H. M. , Eustatia‐Rutten Carmen , Goslings Bernard M. , Stokkel Marcel P. , Arias Alberto M. Pereira , Diamant Michaela , Romijn Johannes A. , Smit Jan W. A. 
Published: June 2003

Summaryobjective Most patients with differentiated thyroid carcinoma (DTC) undergo total thyroidectomy followed by routine radioiodide thyroid remnant ablation. Most centres that routinely perform radioiodide ablation prescribe a low‐iodide diet (LID) to increase the radioiodide accumulation in thyroid remnants. The efficacy of an LID on thyroid remnant ablation, however, has never been demonstrated convincingly.design and methods In a retrospective study, we studied two groups of DTC patients without distant metastases, who had received either a standard diet or an LID during ablation (LID group, n = 59, and control group, n = 61). Both groups were compared for radioiodide uptake in thyroid remnants during ablation and efficacy parameters of remnant ablation, 6 months after ablation. A subgroup without extrathyroidal tumour growth was analysed separately (stages T1–3, N0).results In the total group, the LID during ablation decreased the 24‐h urinary iodide excretion to 26·6 µg compared with 158·8 µg in controls whereas radioiodide uptake in thyroid remnants was increased by 65% (P < 0·001). Six months after ablation, patients were investigated after thyroid hormone withdrawal. In the total group, no significant effects of the LID during ablation were observed on thyroglobulin (Tg) or the percentage of patients with persistent neck activity after 185 MBq 131I. However, in the LID group, 65% of patients without Tg antibodies had undergone successful ablation (defined by absent neck activity and Tg < 2 µg/l) compared with 48% in the control group (P < 0·001). In the subgroup (T1–3, N0), 8% of the patients who had undergone the LID had Tg ≥ 2 µg/l vs. 32% in the control group (P = 0·012), whereas successful ablation was achieved in 71% of patients without Tg antibodies in the LID vs. 45% in the control group (P < 0·001).conclusion We conclude from this study that a low‐iodide diet during thyroid remnant ablation improves the efficacy of this treatment.
GH‐secreting pituitary adenomas infrequently contain inactivating mutations of PRKAR1A and LOH of 17q23–24
Authors: Yamasaki Hiroyuki , Mizusawa Noriko , Nagahiro Shinji , Yamada Shozo , Sano Toshiaki , Itakura Mitsuo , Yoshimoto Katsuhiko 
Published: June 2003

Summaryobjective The molecular events leading to the development of GH‐secreting pituitary tumours remain largely unknown. Gsα (GNAS1) mutations are found in 27–43% of sporadic GH‐secreting adenomas in the Caucasian population, but the frequency of GNAS1 mutations in Japanese and Korean acromegalic patients was reported to be lower, 4–9% and 16%, respectively. Other genes responsible for the tumourigenesis of GH‐secreting pituitary adenomas have not been detected yet. PRKAR1A, which codes for the RIα regulatory subunit of cyclic AMP‐dependent protein kinase A (PKA) on 17q23–24, was recently reported to contain inactivating mutations in some Carney complex families, which involved GH‐secreting adenomas in about 10%. We re‐evaluated the frequency of GNAS1 mutations and investigated PRKAR1A on the hypothesis that it might play a role in the tumourigenesis of GH‐secreting adenomas.design We analysed exons 8 and 9 of GNAS1 and all exons and the exon–intron boundaries of PRKAR1A with the PCR and by direct sequencing using genomic DNA extracted from 32 GH‐secreting pituitary adenomas (30 GH‐secreting adenomas, two GH and PRL‐secreting adenomas) and 28 corresponding peripheral blood samples, and performed loss of heterozygosity (LOH) analysis of 17q23–24 with four microsatellite markers and intragenic markers of PRKAR1A.results Seventeen of 32 (53·1%) tumours showed somatic‐activating mutations of GNAS1: 16 (53·3%) of 30 GH‐secreting adenomas and one of two GH and PRL‐secreting adenomas. Neither inactivating somatic mutations of PRKAR1A nor LOH of 17q23–24 were detected in any of the tumours examined.conclusion We reconfirm the important role of activating mutations of GNAS1 in GH‐secreting adenomas, and conclude that PRKAR1A does not play a significant role in the tumourigenesis.