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G Daniels

Publications and source records attributed to G Daniels.

At least 19 recordsLinked to original sources
PubMed2006

Sequence variation in the 5' untranslated region of the human A4GALT gene is associated with, but does not define, the P1 blood-group polymorphism.

BACKGROUND AND OBJECTIVE: The gene responsible for the P1 polymorphism of the P blood-group system remains unidentified, although the A4GALT gene, whose product is responsible for the production of P(k), has been implicated. No coding differences in A4GALT account for the P1 polymorphism, but homozygosity for two polymorphisms (-551_-550insC and -160A>G) in the 5' untranslated region of the gene has been reported to be unique to Japanese P1- individuals. This study aimed to confirm this correlation in a larger number of British individuals. MATERIALS AND METHODS: Serologically confirmed P1+ (n = 35) and P1- (n = 15) individuals were genotyped for polymorphisms in the 5' untranslated region of A4GALT. RESULTS: In addition to those previously reported, a further polymorphism, -164C>T, was identified. All P1- individuals were homozygous for -551_-550insC and -160G as compared with 10 of 35 (29%) P1+ individuals (P = 0.000003, two-tailed Fisher's exact test). Allele frequencies for all polymorphisms and estimated haplotype frequencies across the region differed significantly between P1+ and P1- groups. CONCLUSIONS: Homozygosity for the A4GALT-551_-550insC and -160G allele is significantly associated with, but not restricted to, the P1- phenotype. No single A4GALT genotype or haplotype was unique to P1- individuals. Thus, A4GALT cannot be unequivocally confirmed as the gene responsible for the P1 phenotype.

5' Untranslated Regions↗
PubMed2005

Late onset neonatal anaemia due to maternal anti-Ge: possible association with destruction of eythroid progenitors.

There have been no reports of severe haemolytic disease of the newborn (HDN) due to Gerbich (Ge) antibodies. Two babies with HDN due to anti-Ge3, both born to the same mother, are described. The anti-Ge appeared in the first pregnancy and was not detectable in the first trimester, the babies' reticulocyte and bilirubin values were not greatly elevated (similar to HDN due to Kell antibodies), and the anaemia in both cases was either not apparent or not severe until 2 to 4 weeks after birth. Ge antigens are found on glycophorins (GPs) C and D; GPC, like Kell, has been shown to be expressed early on erythroid progenitor cells. The maternal anti-Ge3 was shown to promote phagocytosis of Ge+ early erythroid progenitors by monocytes (similar to what has been reported with anti-K and K+ progenitor cells). Thus, anti-Ge3 may cause immune destruction of erythroid progenitors and possibly suppression of erythropoiesis (which would explain the reticulocyte and bilirubin values seen in both cases). Anti-Ge3 appears to be capable of causing severe HDN. We suggest that babies born to mothers with anti-Ge should have their haemoglobin concentrations monitored for signs of anaemia for several weeks after birth. Functional assays may prove useful.

Anemia, Hemolytic↗
PubMed2005

Report of the First International Workshop on molecular blood group genotyping.

The use of molecular genetic technology for blood group typing is becoming routine procedure in many reference laboratories worldwide. A First International Workshop was organized on behalf of the International Society of Blood Transfusion (ISBT) and the International Council for Standardization in Haematology (ICSH). Thirty laboratories that provide a molecular diagnostic service participated in the workshop. Six samples were distributed: two represented DNA from transfusion-dependent patients for testing for multiple polymorphisms; two represented fetal DNA prepared from amniotic fluid for RhD, Rhc and K-testing; and two represented plasma from RhD-negative pregnant women for fetal RhD testing. Error rates varied from 0 to 11% for different polymorphisms. A consensus arising from discussion on the workshop results between participants at a feedback meeting and by e-mail has resulted in seven recommendations for molecular blood group genotyping. Further international workshops will take place every 2 years, with a more limited exercise being organized in the intervening years.

Blood Group Antigens↗
PubMed2004

LU21: a new high-frequency antigen in the Lutheran blood group system.

BACKGROUND AND OBJECTIVES: The Lutheran blood group system comprises 18 antigens numbered LU1 to LU20, with two numbers obsolete. Thirteen antigens are of high frequency. MATERIALS AND METHODS: Serological tests were performed by conventional methods. The monoclonal antibody-specific immobilization of erythrocyte antigens (MAIEA) assay was carried out with monoclonal antibodies to Lutheran glycoprotein. All exons of the LU gene were amplified by the polymerase chain reaction (PCR) and directly sequenced from genomic DNA. RESULTS: A patient was found to have an antibody to a high-frequency red cell antigen during her second pregnancy. The antibody was shown to be Lutheran-related and was distinguished from all reported Lutheran antibodies. MAIEA suggested the antibody was defining a novel epitope in domain 1 of the Lu-glycoprotein. Sequencing of the LU gene revealed a new homozygous single-point mutation, C282G, in exon 3, encoding an Asp94Glu change in the first domain of the Lu-glycoprotein. CONCLUSIONS: The antibody detected a new high-frequency Lutheran antigen, numbered LU21, that appears to result from an Asp94Glu substitution in the first, N-terminal domain of the Lu-glycoprotein.

Antibodies, Monoclonal↗
PubMed2004

Fetal blood group genotyping from DNA from maternal plasma: an important advance in the management and prevention of haemolytic disease of the fetus and newborn.

The cloning of blood group genes and subsequent identification of the molecular bases of blood group polymorphisms has made it possible to predict blood group phenotypes from DNA with a reasonable degree of accuracy. The major application of this technology, which has now become the standard of care, is the determination of a fetal RHD genotype in women with anti-D, to assess whether the fetus is at risk of haemolytic disease of the fetus and newborn (HDFN). Initially, the procurement of fetal DNA required the invasive procedures of amniocentesis or chorionic villus sampling. Since the discovery of fetal DNA in maternal plasma in 1997, the technology of detecting an RHD gene in this very small quantity of fetal DNA has developed rapidly, so that non-invasive fetal D typing can now be provided as a diagnostic service for D-negative pregnant women with anti-D. Within a few years, it is probable that fetuses of all D-negative pregnant women will be tested for RHD, to establish whether the mother requires antenatal anti-D immunoglobulin prophylaxis.

Blood Group Antigens↗
PubMed2002

Flux flow of Abrikosov-Josephson vortices along grain boundaries in high-temperature superconductors.

Low-angle grain boundaries (GBs) in superconductors exhibit intermediate Abrikosov vortices with Josephson cores, whose length l along GB is smaller than the London penetration depth, but larger than the coherence length. We found an exact solution for a periodic vortex structure moving along GBs in a magnetic field H and calculated the flux flow resistivity R(F)(H), and the nonlinear voltage-current characteristics. The predicted R(F)(H) dependence describes well our experimental data on 7 unirradiated and irradiated YBa(2)Cu(3)O(7) bicrystals, from which the core size l(T), and the intrinsic depairing density J(b)(T) on nanoscales of a few GB dislocations were measured for the first time. The observed J(b)(T) = J(b0)(1-T/T(c))(2) indicates a significant order parameter suppression on GB.

Journal Article↗
PubMed2002

JAHK: a low frequency antigen associated with the rG complex of the Rh blood group system.

We have investigated a 'new' low frequency antigen JAHK, which is a marker for the rare Rh gene complex rG. The rG haplotype does not produce any D, c or E antigens, but does produce a strong G antigen. The rG haplotype [d(C)(e)G] is associated with weak C and weak e antigens. Three unrelated rG/dce individuals and one rG/rG propositus were JAHK+. In addition, three propositi whose red cells had a typical expression of C and/or e antigen, which could not be shown to be rG because of a normal D antigen produced by the haplotype in trans, were also JAHK+. Families of three of the propositi demonstrate the inheritance of JAHK as a Mendelian dominant character. It is likely that the JAHK antigen results from conformational changes in an RhCcEe protein that has the amino acid characteristic of c antigen at position 16 and the amino acid residues characteristic of C antigen at positions 60, 68, and 103. JAHK has been assigned the number RH53.

Blood Grouping and Crossmatching↗
PubMed2001

A century of human blood groups.

During the course of the twentieth century, at least 270 authenticated alloantigens have been recognised on the red cell surface. Most of these have been classified into 26 blood group systems, each of which represents a single gene or a cluster of two or three closely-linked homologous genes. Most blood group polymorphisms result from single nucleotide changes encoding amino acid substitutions in cell surface proteins. Many other mechanisms, including recombination between homologous genes, are also involved, especially in the complex Rh and MNS systems. There are at least three common molecular backgrounds to the RhD-negative phenotype. Some blood group antigens are carbohydrates, the polymorphisms resulting from mutations within genes encoding glycosyltransferases. Red cell surface proteins perform a variety of functions. For some the functions are well understood, but for most they can only be surmised from the structure of the protein. Putative functions include, membrane transport, cell adhesion, complement inactivation, binding chemokines, and anchoring the plasma membrane to the cytoskeleton. Some erythroid cell surface antigens may serve their primary purpose during erythropoiesis. Analysis of the development of these proteins on erythroid cells during erythropoiesis, ex vivo, has provided clues to their functions and a useful set of markers for the study of erythropoiesis.

Blood Group Antigens↗
PubMed2001

McLeod neuroacanthocytosis: genotype and phenotype.

McLeod syndrome is caused by mutations of XK, an X-chromosomal gene of unknown function. Originally defined as a peculiar Kell blood group variant, the disease affects multiple organs, including the nervous system, but is certainly underdiagnosed. We analyzed the mutations and clinical findings of 22 affected men, aged 27 to 72 years. Fifteen different XK mutations were found, nine of which were novel, including the one of the eponymous case McLeod. Their common result is predicted absence or truncation of the XK protein. All patients showed elevated levels of muscle creatine phosphokinase, but clinical myopathy was less common. A peripheral neuropathy with areflexia was found in all but 2 patients. The central nervous system was affected in 15 patients, as obvious from the occurrence of seizures, cognitive impairment, psychopathology, and choreatic movements. Neuroimaging emphasized the particular involvement of the basal ganglia, which was also detected in 1 asymptomatic young patient. Most features develop with age, mainly after the fourth decade. The resemblance of McLeod syndrome with Huntington's disease and with autosomal recessive chorea-acanthocytosis suggests that the corresponding proteins--XK, huntingtin, and chorein--might belong to a common pathway, the dysfunction of which causes degeneration of the basal ganglia.

Adult↗
PubMed2001

Six unaffected livebirths following preimplantation diagnosis for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a severe neurodegenerative autosomal recessive disorder, second only in frequency to cystic fibrosis. In its most severe form, SMA type I (Werdnig-Hoffman), death invariably ensues before age 2 years from respiratory failure or infection. Around 98% of clinical cases of SMA are caused by the homozygous absence of a region of exons 7 and 8 of the telomeric copy of the SMN gene (SMN1) on chromosome 5. We have developed a novel means of preimplantation diagnosis of SMA using a nested polymerase chain reaction (PCR) amplification of exon 7 of SMN, followed by a HinfI restriction digest of the PCR product enabling the important SMN1 gene to be distinguished from the centromeric SMN2 gene which has no clinical phenotype. This method was designed to reduce the likelihood of misdiagnosis. Five couples were treated using this method. Four proceeded to embryo transfer which resulted in six liveborns (one singleton, one twin and one triplet), all free of SMA. Embryo transfer was not performed in one cycle because of PCR contamination.

Adult↗
PubMed2001

McLeod syndrome: a novel mutation, predominant psychiatric manifestations, and distinct striatal imaging findings.

The McLeod syndrome is an X-linked disorder caused by mutations of the XK gene encoding the XK protein. The syndrome is characterized by absent Kx erythrocyte antigen, weak expression of Kell blood group system antigens, and acanthocytosis. In some allelic variants, elevated creatine kinase, myopathy, neurogenic muscle atrophy, and progressive chorea are found. We describe a family with a novel point mutation in the XK gene consisting of a C to T base transition at nucleotide position 977, introducing a stop codon. Among seven affected males, five manifested with psychiatric disorders such as depression, bipolar disorder, or personality disorder, but only two presented with chorea Positron emission tomography and magnetic resonance volumetry revealed reduced striatal 2-fluoro-2-deoxy-glucose (FDG) uptake and diminished volumes of the caudate nucleus and putamen that correlated with disease duration. In contrast, none of 12 female mutation carriers showed psychiatric or movement disorders. However, a semidominant effect of the mutation was suggested by erythrocyte and blood group mosaicism and reduced striatal FDG uptake without structural abnormalities. Therefore, patients with psychiatric signs or symptoms segregating in an X-linked trait should be examined for acanthocytosis and Kell/Kx blood group serology.

Adolescent↗
PubMed2000

The presence of an RHD pseudogene containing a 37 base pair duplication and a nonsense mutation in africans with the Rh D-negative blood group phenotype.

Antigens of the Rh blood group system are encoded by 2 homologous genes, RHD and RHCE, that produce 2 red cell membrane proteins. The D-negative phenotype is considered to result, almost invariably, from homozygosity for a complete deletion of RHD. The basis of all PCR tests for predicting fetal D phenotype from DNA obtained from amniocytes or maternal plasma is detection of the presence of RHD. These tests are used in order to ascertain the risk of hemolytic disease of the newborn. We have identified an RHD pseudogene (RHD psi) in Rh D-negative Africans. RHDpsi contains a 37 base pair (bp) insert in exon 4, which may introduce a stop codon at position 210. The insert is a sequence duplication across the boundary of intron 3 and exon 4. RHDpsi contains another stop codon in exon 6. The frequency of RHDpsi in black South Africans is approximately 0.0714. Of 82 D-negative black Africans, 66% had RHDpsi, 15% had the RHD-CE-D hybrid gene associated with the VS+ V- phenotype, and only 18% completely lacked RHD. RHDpsi is present in about 24% of D-negative African Americans and 17% of D-negative South Africans of mixed race. No RHD transcript could be detected in D-negative individuals with RHDpsi, probably as a result of nonsense-mediated mRNA decay. Existing PCR-based methods for predicting D phenotype from DNA are not suitable for testing Africans or any population containing a substantial proportion of people with African ethnicity. Consequently, we have developed a new test that detects the 37 bp insert in exon 4 of RHDpsi. (Blood. 2000; 95:12-18)

Amino Acid Sequence↗
PubMed2000

Induction or suppression of a B cell-specific response to self antigen in vivo is dependent upon dendritic cell activation via the TNF-alpha receptor at the time of antigen uptake.

In this study we show that the retinal autoantigen, S-antigen, contains a functional TNF-alpha homologous domain which stimulates maturation and differentiation of cultured dendritic cells (DC) or tissue DC via the p55 TNF-alpha receptor. Tissue DC became more dendritiform in shape, and migrated into culture supernatant. S-antigen also stimulated accumulation of cell surface MHC class II antigen with a corresponding loss of acidic intracellular vesicles, and induced IL-1beta and IL-12 mRNA expression in cultured bone marrow-derived DC. In addition, cultured splenic DC primed immune responses to S-antigen in vivo in the absence of other, exogenous cytokine sources. DC pulsed with either retinal S-antigen or another retinal autoantigen, interphotoreceptor retinoid binding protein (IRBP), were able to stimulate naive T cell proliferation in vitro, but only S-antigen-pulsed DC were able to induce an immune response in vivo and initiate antibody class switching. In contrast, IRBP-pulsed DC had no detectable in vivo priming effect and IgG antibody levels remained suppressed even after immunization with IRBP in complete Freund's adjuvant. These results indicate that DC from the same precursor population can either induce or suppress a B cell-specific response to self antigen in vivo, the outcome being dependent upon DC activation at the time of antigen uptake and presentation.

Animals↗
PubMed2000

HNA-1a, HNA-1b, and HNA-1c (NA1, NA2, SH) frequencies in African and American Blacks and in Chinese.

The granulocyte antigens HNA-1a, -1b, and -1c (formerly named NA1, NA2 and SH) which reside on the neutrophil FcgammaReceptor IIIb (FcgammaRIIIb) play a major role in immune neutropenias and pulmonary transfusion reactions. In an attempt to shed some light on the origin and history of these antigens we typed the DNA of Blacks from South Africa (n=99), and Ghana (n=27), of 56 African Americans, and of 138 Chinese from Taiwan for HNA-1a,-1b, and -1c antigens using polymerase chain reaction with sequence-specific primers (PCR-SSP). In African and American Blacks, the HNA-1b antigen was more frequent than HNA-1a (77 vs. 67% and 77 vs. 59%, respectively). In contrast, in Chinese HNA-1a was more frequent than HNA-1b (91 vs. 54%). We observed 3 individuals with FcgammaRIIIB deficiency among the 126 tested African Blacks indicating a higher frequency of FcgammaRIIIB deficiency in Blacks than the reported 0.1% in Europeans. In addition, the frequency of HNA-1c in African and American Blacks (38 and 23%, respectively) was higher than the reported 5% in Europeans. Among the 57 HNA-1c (+) Blacks, all were HNA-1b (+) but only 26 were HNA-1a (+) supporting the idea that the HNA-1c antigen is the result of an additional point mutation in the allele coding for HNA-1b. Recently, HNA-1a, -1b, and -1c (+) Europeans have been reported to have three distinct FcgammaRIIIB genes. Among 26 Blacks who had been typed HNA-1a,b,c (+) by PCR-SSP we identified only 7 having three FcgammaRIIIB genes by DNA sequencing. When we sequenced the DNA of 6 HNA-1a,b,c (+) Europeans we found 4 of the individuals had three FcyRIIIB genes. Therefore, we assume that in Africa the point mutation occurred first in the HNA-1b allele resulting in the HNA-1c allele and the FcgammaRIIIB gene duplication took place later.

Asian People↗