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P Tippett

Publications and source records attributed to P Tippett.

At least 19 recordsLinked to original sources
PubMed1996

The Rh antigen D: partial D antigens and associated low incidence antigens.

The expression of the Rh antigen D varies quantitatively and qualitatively (partial D); published information and 15 years' work studying D variants are discussed in this review. D epitopes correspond to the reaction patterns of monoclonal anti-D with partial D antigens. Partial D antigens can be reported in terms of their D epitopes but the epitope profile of cells with a quantitative variant of D (weak D) is difficult to determine reliably by haemagglutination tests. Nine partial D antigens, categories II-VII, DFR and two not previously reported, are identified by their epitope profiles and by association with low incidence antigens. Monoclonal anti-D recognize 16 D epitopes and more epitopes are anticipated. The specificities of polyclonal anti-D made by people with partial D antigens are considered in terms of possible D epitope specificities: recognized epitope specificities, or combination thereof, were not able to account for all observed reaction patterns of anti-D made by immunized individuals with partial D phenotypes. An attempt is made to understand partial D antigens and their associated low incidence antigens in terms of the molecular genetic information available.

Antibodies, Monoclonal↗
PubMed1996

The D antigen characteristic of RoHar is a partial D antigen.

The results of testing RoHarr cells with panels of monoclonal anti-D suggest that the D antigen (referred to as DHar) encoded by the haplotype (D)c(e) Rh33 is a partial D antigen. IgM monoclonal anti-D are more efficient than IgG monoclonal anti-D in detecting DHar.DHar expresses some but not all of both epD5 and epD6/7 and appears to lack epD1-epD4, epD8 and epD9.

Epitopes↗
PubMed1995

Investigation of the biochemical relationship between the blood group antigens Xga and CD99 (12E7 antigen) on red cells.

The biochemical relationship between the red cell antigens Xga and the MIC2 gene product, CD99--previously designated the 12E7 antigen--has been examined by immunoblotting and immunoprecipitation analyses of the protein molecules bearing these antigens. Immunoblotting of membrane components and Xga-immunoprecipitates with anti-Xga has shown that Xga antigen is carried on a broad band of apparent molecular weight (Mr)) 24,500-29,500, which consists of a dark stained component at M(r)24,500 and a more diffusely stained component at approximately M(r) 26,500-29,500. Immunoblotting of membrane components and 12E7-immunoprecipitates with 12E7, and RFB-1 and NaM123 which also recognise CD99, distinguished two bands of M(r) 30,000 and 32,000. A non-radioactive immunoprecipitation technique was employed, which uses chemiluminescence detection of biotin-labelled red cell proteins. The protein of M(r) 32,000, which carries CD99, was identified by this method and the red cell quantitative polymorphism of CD99 was demonstrated. When the Xga protein was precipitated from biotin-labelled red cells, a protein of M(r) 32,000 was coprecipitated. This suggests that the proteins carrying the Xga antigen and CD99 are associated in the membrane.

12E7 Antigen↗
PubMed1995

Pulsatile GnRH stimulates normal cyclic ovarian function in amenorrheic lactating postpartum women.

The postpartum period is characterized hormonally by elevated levels of PRL and low levels of gonadotropins and sex steroids. In breast feeding, this state of postpartum amenorrhea can persist for an extended period, even though PRL levels decrease slowly. Although the action of PRL on multiple target sites has frequently been suggested as the cause of this ovarian quiescence, a suckling-induced alteration in hypothalamic gonadotropin-releasing hormone (GnRH) production has also been hypothesized. To test this latter hypothesis, we provided a uniform pulsatile GnRH stimulus to eight exclusively breast-feeding women for an 8-week duration beginning at 4 weeks postpartum. Five women with functional hypothalamic amenorrhea served as a comparison group. All women received GnRH administered at a dose of 200 ng/kg every 90 min sc via a portable infusion pump. Serial blood sampling for LH, FSH, and PRL was performed weekly for 5 h at 10-min intervals beginning immediately before initiation of GnRH, during the period of GnRH, and 1 week after the cessation of GnRH. The women collected daily urine aliquots for estrone-3-glucuronide, pregnanediol-3-glucuronide, and LH determinations. Serial transvaginal sonography was used to monitor follicular development. Before GnRH treatment the urinary steroid and serum gonadotropin levels of the two groups were low and similar. As expected, PRL levels were higher in the postpartum women (87 micrograms/mL vs. 4.25 micrograms/L, P < 0.05). After initiation of pulsatile GnRH, LH values increased and FSH values decreased in both groups. The LH increase with GnRH was significantly greater in the breast-feeding group than in the hypothalamic amenorrhea group (19.75 mIU/mL vs. 12.34 mIU/mL, P < 0.05). Analysis of pulse frequency and amplitude revealed a nearly complete 1:1 induction of LH pulses by the exogenous GnRH in both groups, with the breast-feeding group showing a greater amplitude (12.26 mIU/mL vs. 5.34 mIU/mL, P < 0.05). The cycle lengths, urinary steroids, and vaginal ultrasonography demonstrated a more rapid initial ovarian responsiveness in the breast-feeding group, as determined by the length of the first follicular phase. The breast-feeding group also showed a brisker ovarian response, as evidenced by a greater number of follicles that were 12 mm or greater (2.3 vs. 1.2, P < 0.05), and a greater luteal phase peak and integrated pregnanediol excretion, respectively (3.02 micrograms/L creatinine and 39.87 micrograms/L creatinine/cycle vs. 1.89 micrograms/L creatinine and 7.69 micrograms/L creatinine/cycle, P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

PBDX is the XG blood group gene.

We have identified the Xga antigen, encoded by the XG blood group gene, by employing rabbit polyclonal and mouse monoclonal antibodies raised against a peptide derived from the N-terminal domain of a candidate gene, referred to earlier as PBDX. In indirect haemagglutination assays, these anti-peptide antibodies react with Xg(a+) but not Xg(a-) erythrocytes. In antibody-specific immobilization of antigen (ASIA) and immunoblot assays, the anti-peptide antibodies react with the same molecule as does human anti-Xga. Therefore, by its identity with PBDX, Xga is identified as a cell-surface protein that is 48% homologous to CD99 (previously designated the 12E7 antigen), the product of MIC2 which is tightly linked to XG. PBDX is renamed here XG.

12E7 Antigen↗
PubMed1994

FPTT is a low-incidence Rh antigen associated with a "new" partial Rh D phenotype, DFR.

BACKGROUND: Several Rh D phenotypes with partial D antigens are recognized. Some partial D antigens are associated with low-incidence Rh antigens. New partial D antigens are revealed by an atypical pattern of reactions with anti-D. STUDY DESIGN AND METHODS: The reactions of D variant cells with panels of monoclonal anti-D and with antibodies to low-incidence antigens were compared to those of known D categories to identify a new Rh D phenotype. The inheritance of partial D antigens was studied by Rh phenotyping of the families of the probands. Standard serologic methods were used and family data were analyzed. RESULTS: A new Rh D phenotype, to be called DFR, was identified in 17 probands, two of whom had made anti-D. The partial D antigen carries epD3, epD4, and epD9 and lacks epD8. The presence of other D epitopes is ambiguous; different answers were obtained for the same sample with different monoclonal anti-D of the same apparent epitope specificity. The immunoglobulin class of the anti-D was important: IgG were more successful than IgM monoclonal anti-D in detecting the partial D of DFR. Family studies showed that DFR traveled with Ce more frequently than with cE. The low-incidence antigen FPTT (International Society of Blood Transfusion number 700048) was found on all DFR samples. Family studies demonstrated that FPTT is, as suspected, part of the complex Rh system. CONCLUSION: The partial D of the Rh D phenotype, DFR, is recognized by its pattern of reactions with monoclonal anti-D and its association with the low-incidence antigen FPTT, FPTT has now been numbered Rh50.

Antibodies, Monoclonal↗
PubMed1994

Application of the MAIEA assay to the Kell blood group system.

The monoclonal antibody-specific immobilisation of erythrocyte antigens (MAIEA) test has been employed to investigate the Kell system using five monoclonal antibodies which recognise high frequency epitopes on the 93,000-molecular weight Kell glycoprotein: BRIC 18, BRIC 68, BRIC 107, BRIC 203 and 6-22. BRIC 107, which has anti-k-like (KEL2) specificity, identifies a distinct epitope, whilst competitive binding assays suggested that BRIC 203 (anti-Kpbc), BRIC 18, BRIC 68 and 6-22 (anti K14) comprise an overlapping set of epitopes. The MAIEA assay has been very successful in confirming the assignment of most of the Kell and para-Kell antigens to the Kell protein. Due to the competitive nature of the assay and the fact that the monoclonal antibodies bind to different regions, the results also suggest the relative positions of some of the Kell antigens on the Kell protein; these appear to be located in at least five spatially distinct regions.

Antibody Specificity↗
PubMed1994

Production of a murine monoclonal antibody to the low-incidence red cell antigen Wra: characterisation and comparison with human anti-Wra.

The production of a monoclonal antibody which detects the low-incidence red cell antigen Wra is described. The antibody (BGU1-WR) was isolated following immunization of BALB/tk mice with Wr(a+) cells. BGU1-WR is an IgG1 antibody and reacted in a manner similar to human polyclonal anti-Wra with untreated, protease treated and chemically modified Wr(a+) cells.

Animals↗
PubMed1994

Comparative immunochemical analysis of Wra and Wrb red cell antigens.

This paper describes immunoblotting and immunoprecipitation studies using monoclonal anti-Wra and anti-Wrb antibodies to investigate the nature of the low-incidence blood group antigen, Wra and its high-incidence allelic antigen Wrb. No membrane components were identified by the immunoblotting experiments. Immunoprecipitation studies confirmed that the Wrb antigen involves both glycophorin A and band 3. The monoclonal anti-Wra, BGU1-WR, failed to immunoprecipitate these or any othe red cell membrane component. The significance of these findings is discussed.

Alleles↗
PubMed1994

Mg+ MNS blood group phenotype: further observations.

Red cells carrying the low-frequency MNS antigen Mg reacted with the only example of anti-DANE, an antibody which had previously defined the GP. Dane (Mi.IX) phenotype. Furthermore, Mg+ cells reacted with the original anti-Mur (serum of Mrs. Murrell), but with none of 14 other anti-Mur. Therefore, Mg+ cells carry both DANE antigen and an atypical Mur antigen. Immunoblotting of membranes from Mg+ cells with anti-M, and with eluates prepared from anti-Mg and Mrs. Murrell's serum demonstrated a glycophorin A (GPA) molecule whose mobility was increased by an apparent M(r) of about 3,000 presumably due to the loss of the three O-glycans known to be absent from Mg-active GPA.

Amino Acid Sequence↗
PubMed1993

Quantitation of D sites on selected 'weak D' and 'partial D' red cells.

Measurements have been made of the number of available sites on 10 examples of red cells in which the only abnormality appeared to be a quantitative reduction in the expression of D (weak D cells); these estimates were carried out using three monoclonal anti-D antibodies, Fog-1, Brad-3 and Los-2. The values varied with the monoclonal antibody that was used and fell within the range of 170-1,870 sites/cell. A further 3 examples of weak D cells which had brought about immunisation following transfusion were found to have between 390 and 1,470 sites per red cell. The implications of the D site density on the immunogenicity of weak D cells are discussed. The number of sites on red cells with structurally abnormal D (partial D cells) were also estimated, using the antibody Fog-1. Four of the 5 examples of cells of category IVa (probable phenotype Ror) were found to have a high expression of D (range 29,300-41,300), but the available D sites of categories DVa, DVIa, and DVII were considerably reduced (< 500, < 500 and 2,400-7,500 sites/cell, respectively). As a working hypothesis, it is suggested that there are two types of genetic abnormality leading to an abnormal expression of D. First, a defect in genomic DNA leading only to a quantitative reduction in the number of available D sites; this genomic lesion should be termed 'weak D'. Secondly, genomic defects leading to amino acid sequence abnormalities and structural change in the D polypeptide; these lesions should be collectively known as 'partial D'.

Antibodies, Monoclonal↗
PubMed1993

Use of the MAIEA technique to confirm the relationship between the Cromer antigens and decay-accelerating factor and to assign provisionally antigens to the short-consensus repeats.

The MAIEA (monoclonal-antibody-specific immobilisation of erythrocyte antigens) assay has recently been developed for the assignment of red cell antigens, recognised by human alloantisera, to particular membrane components of the red cell membrane. This technique detects trimolecular complexes formed by the reaction of a human antibody and a mouse antibody with a particular red cell protein. A positive reaction, in an ELISA-type detection procedure, occurs if the epitopes to the human and mouse antibodies are present on the same membrane component but at different regions. In this report, we show how the MAIEA assay can be used to confirm the relationship between Cromer system antigens and the complement-regulatory protein, decay-accelerating factor (DAF, CD 55). In addition, the location of the antigens along the protein is postulated by using three anti-DAF monoclonal antibodies with specificities to different regions of DAF. Tca and Esa are assigned provisionally to the first short-consensus repeat (SCR), UMC to the second SCR, Dra to the third SCR and Cra, WESa and WESb to the fourth SCR or to the serine/threonine rich region of the DAF protein.

Antibodies, Monoclonal↗
PubMed1993

Low-incidence red cell antigen ELO (700.51): evidence for exclusion from thirteen blood group systems.

Genetic studies of the families of two unrelated propositi prove that the low-incidence antigen ELO (ISBT No. 700.51) is not part of the MNS, Rh, Duffy, Kidd, Xg, Kx and Gerbich blood group systems and indicate that it is probably not part of the Lutheran, Scianna, Dombrock or Colton systems. Serological studies indicate exclusion from the Kell and Chido/Rodgers systems. Although the ELO antigen is rare, anti-ELO is not uncommon in sera containing at least one specificity for a low-incidence antigen.

Blood Group Antigens↗
PubMed1992

Molecular analysis of human glycophorin MiIX gene shows a silent segment transfer and untemplated mutation resulting from gene conversion via sequence repeats.

The human glycophorin (HGp) loci that define the red blood cell surface antigens of the MNSs blood group system exhibit considerable allelic variation. Previous studies have identified gene conversion events involving HGpA(alpha) and HGpB(delta) that produced delta-alpha-delta hybrid genes which differ in the location of breakpoints. This report presents the molecular analysis of HGpMilX, the first example of a reverse alpha-delta-alpha hybrid gene that specifies a newly described phenotype of the Miltenberger complex. A novel restriction fragment unique to the HGpMilX gene was detected by Southern blot hybridization. The structure of the genomic region encoding the entire extracellular domain of the MilX protein was determined. Nucleotide sequencing of amplified genomic DNA showed that a silent segment of the HGpB(delta) gene had been transposed to replace the internal part of exon III in the HGpA(alpha) gene, thereby resulting in the formation of the MilX allele with an alpha-delta-alpha configuration. The proximal alpha-delta breakpoint was found to be flanked by a direct repeat of the acceptor splice site, whereas the distal delta-alpha breakpoint was localized to a palindromic region. This DNA rearrangement, with a minimal transfer of 16 templated nucleotides and a single mutation of untemplated adenyl nucleotide, not only created two intraexon hybrid junctions but transactivated the expression of a new stretch of amino acid residues in the MilX protein. Such a segment replacement may have occurred through the directional transfer from one duplex to the other via the mechanism of gene conversion. The occurrence of HGpMilX as another hybrid derived from parts of parent genes underlines the role of the recombinational "hotspot" in the generation of allelic diversity in the glycophorin family.

Amino Acid Sequence↗