1,720,969 research outputs found
FAOD (Malattie ossidazione degli acidi grassi): Indagini Biochimiche e Genetico-Molecolari in ambito di un programma di Screening Neonatale
Full text linkLa ricerca si è resa possibile grazie al conferimento della borsa di studio -Anno 2011/2012- da parte della Fondazione Achille Lattuc
HLA class I expression on human platelets is highly variable and correlates with distinct allele group frequencies
Full text linkBackground: Human leukocyte antigen (HLA) class I molecules are expressed on platelets and can represent a source of alloimmunization in recipients of platelet transfusions. HLA mismatch between donors and recipients may be associated with the induction of anti-HLA antibodies, which can culminate in refractoriness to platelet transfusions. In the present study we analyzed HLA allele group frequencies and HLA expression levels on human platelets from blood donors.
Materials and methods: Platelet-rich plasma was collected from 139 donors to monitor platelet HLA class I expression by flow cytometry. DNA from donors with high and low platelet HLA expression was used in the genotype studies. Frequencies of large and normal-sized platelet subpopulations were determined and HLA class I expression was studied. Mean platelet volume (MPV) and platelet large-cell ratio (P-LCR) were analyzed in both groups of donors.
Results: The analysis showed variable platelet HLA class I expression with significant differences among donors. HLA class I allele group frequencies in donors with high and low platelet HLA expression showed distinctive genotypic features strictly related to expression level. The main allele groups found in samples with high platelet HLA class I expression were HLA-A*02, -A*68, -B*15, -B*49, and -C*03. Platelet HLA class I expression did not change over time or during freezing-thawing cycles. The analysis of platelet subpopulations showed a statistically significant higher expression of HLA class I molecules on large platelets than on normal-sized platelets. Moreover, donors with high HLA class I expression showed a higher frequency of large platelets (p<0.0001). The analysis of P-LCR in both groups of donors showed a statistically significant difference (p<0.05) within high HLA-expressing donors.
Discussion: Our data suggest an allele-dependent expression of HLA class I molecules on human platelets with distinct HLA allele group frequencies and different platelet subpopulation frequencies among blood donors
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
A new asymptomatic case of methylmalonic acidemia (MMA) identified by MS/MS newborn screening
No full textA newborn screening pilot study using tandem mass spectrometry has been set up since 2003. To date more than 15000 newborns have been screened.
We reported a newborn affected by benign MMA identified by MS/MS. The analysis of derivatized acylcarnitines and amino acids in dried blood spot was performed using PerkinElmer NeoGram MS2 Kit. The analysis of patient’s blood sample obtained at 3 days of life showed an elevation of propionylcarnitine (C3: 4.38 μM) slightly below the cut-off value (4.6 μM) and a C3/C2 ratio higher than cutoff ( C3/C2 0.20, cutoff 0.18), therefore a repeat of blood spot collection was requested. This second sample, obtained at the age of 28 days, showed a marked increase of C3 and C3/C2. The organic acid analysis in urine demonstrated an increase of methylmalonic acid. The (hydroxy)cobalamin administration (loading) test was carried out and no significant reduction of methylmalonic acid excretion in urine was found. Therefore a deficiency of methylmalonyl-CoA mutase (EC 5.4.99.2) enzyme was suspected. Molecular genetic analysis was performed on the 13 exons and intron- exon boundaries of methylmalonyl-CoA mutase gene (c.DNA NM_00025; g.DNA NT_007592) were analyzed by direct sequencing. The patient resulted compound heterozygote for two already described mutations: N219Y (c.655A>T) and R694W (c.2080C>T). The mutations were confirmed in the parents.
The N219Y is a quite frequent mutation in MMA (19% alleles in Caucasians). It was already described associated to severe phenotype (mut0) with low or absent residual enzymatic activity. The Asn 219 is a conserved amino acid and is located at the fourth β strand of the substrate binding (α/β)8 barrel. Modelling analysis suggests that this mutation gives impaired folding and/or poor stability of the protein. The R264W mutation was associated to a milder phenotype (mut-). This residue is located in the protein pocket binding dimethylbenzimidazole portion of cobalamin molecule. Being the protein an homodimer, we suppose that the compound heterozigosity mut0/mut- gives enough molecules with residual enzymatic activity to manifest a milder phenotype.
Conclusions: 1- Benign MMAs can be identified using MS/MS in newborn screening. MMA disorders may not produce significant concentrations of C3 and will not be detected. The evaluation of C3/C2 ratio is important to reduce the number of false positive and false negative results.
2- Molecular analysis could be an important tool to predict clinical phenotype
3-The early detection and therapy have had a favorable effect on prevention of metabolic decompensation. However, a long-term study is necessary to assess whether the early detection and intervention may improve the outcome
Analysis of Children and Adolescents with Familial Hypercholesterolemia
No full textObjective To evaluate the effectiveness of criteria based on child-parent assessment in predicting familial hypercholesterolemia
(FH)-causative mutations in unselected children with hypercholesterolemia.
Study design LDLR, APOB, and PCSK9 genes were sequenced in 78 children and adolescents (mean age 8.4 ± 3.7
years) with clinically diagnosed FH. The presence of polygenic hypercholesterolemia was further evaluated by genotyping
6 low-density lipoprotein cholesterol (LDL-C)-raising single-nucleotide polymorphisms.
Results Thirty-nine children (50.0%) were found to carry LDLR mutant alleles but none with APOB or PCSK9
mutant alleles. Overall, 27 different LDLR mutations were identified, and 2 were novel. Children carrying mutations
showed higher LDL-C (215.2 ± 52.7 mg/dL vs 181.0 ± 44.6 mg/dL, P < .001) and apolipoprotein B levels
(131.6 ± 38.3 mg/dL vs 100.3 ± 30.0 mg/dL, P < .004), compared with noncarriers. A LDL-C of ~190 mg/dL was the
optimal value to discriminate children with and without LDLR mutations. When different diagnostic criteria were
compared, those proposed by the European Atherosclerosis Society showed a reasonable balance between sensitivity
and specificity in the identification of LDLR mutations. In children without mutation, the FH phenotype was
not caused by the aggregation of LDL-C raising single-nucleotide polymorphisms.
Conclusions In unselected children with hypercholesterolemia, LDL-C levels >190 mg/dL and a positive family history
of hypercholesterolemia appeared to be the most reliable criteria for detecting FH. As 50% of children with suspected
FH did not carry FH-causing mutations, genetic testing should be considere
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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