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B Brewer

Publications and source records attributed to B Brewer.

16 recordsLinked to original sources

Fine mapping of a gene responsible for regulating dietary cholesterol absorption; founder effects underlie cases of phytosterolaemia in multiple communities.

Sitosterolaemia (also known as phytosterolaemia, MIM 210250) is a rare recessive autosomal inherited disorder, characterised by the presence of tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. The defective gene is hypothesised to play an important role in regulating dietary sterol absorption and biliary secretion, thus defining a molecular mechanism whereby this physiological process is carried out. The disease locus was localised previously to chromosome 2p21, in a 15 cM interval between microsatellite markers D2S1788 and D2S1352 (based upon 10 families, maximum lodscore 4.49). In this study, we have extended these studies to include 30 families assembled from around the world. A maximum multipoint lodscore of 11.49 was obtained for marker D2S2998. Homozygosity and haplotype sharing was identified in probands from non-consanguineous marriages from a number of families, strongly supporting the existence of a founder effect among various populations. Additionally, based upon both genealogies, as well as genotyping, two Amish/Mennonite families, that were previously thought not to be related, appear to indicate a founder effect in this population as well. Using both homozygosity mapping, as well as informative recombination events, the sitosterolaemia gene is located at a region defined by markers D2S2294 and Afm210xe9, a distance of less than 2 cM.

Arteriosclerosis↗

An ATP-binding cassette gene (ABCG5) from the ABCG (White) gene subfamily maps to human chromosome 2p21 in the region of the Sitosterolemia locus.

We characterized a new human ATP-binding cassette (ABC) transporter gene that is highly expressed in the liver. The gene, ABCG5, contains 13 exons and encodes a 651 amino acid protein. The predicted protein is closely related to the Drosophila white gene and a human gene, ABCG1, which is induced by cholesterol. This subfamily of genes all have a single ATP-binding domain at the N-terminus and a single C-terminal set of transmembrane segments. ABCG5 maps to human chromosome 2p21, between the markers D2S117 and D2S119. The abundant expression of this gene in the liver suggests that the protein product has an important role in transport of specific molecule(s) into or out of this tissue.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

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Journal Article↗

Correction of the PNH defect by GPI-anchored protein transfer.

Hemolytic anemia is a major feature of paroxysmal nocturnal hemoglobinuria (PNH). Intravascular red blood cell (RBC) destruction is caused by increased sensitivity of the abnormal erythrocyte to complement-mediated lysis, due to the GPI absence of a membrane-bound glycosylphosphatidylinositol (GPI)-linked protein, which functions as an inhibitor of reactive lysis (CD59). Both in vivo and in vitro models have suggested the feasibility of cell-to-cell transfer of GPI proteins, and patients with hemolysis could potentially benefit from transfer of CD59 to their deficient erythrocytes. We studied the ability of RBC components prepared from outdated packed RBC collections, as well as high-density lipoprotein (HDL) preparations, rich in CD55 and CD59, to promote protein transfer, as assessed by flow cytometry, immunoblotting, and susceptibility to complement-mediated lysis. By flow cytometry, CD55 and CD59 were present on RBC-derived microvesicles that stained with an antiglycophorin antibody Ab; in addition, soluble CD59 and CD55 were detected by immunoblot in soluble fractions eluated from RBC units stored for more than 35 days, but not in fresh blood. Both commercial HDL preparations and those prepared in our laboratory contained CD55 and CD59, as assayed by immunoblot. When RBC that were deficient (GPI)-anchored protein, obtained from five patients, with PNH were incubated with HDL preparations for 2 to 4 hours, there was significant transfer of both proteins to the cell surface, as demonstrated by flow cytometry. Washed RBC microvesicles, prepared by ultrasonification, also mediated transfer of GPI-linked proteins to deficient RBC. Pretreatment of microvesicles, RBC eluate preparations, and HDL with phosphatidylinositol-specific, phospholipase C, abrogated protein transfer to deficient cells, indicating that increased cell-associated CD55 and CD59 levels were related to insertion of the intact GPI moiety, rather than to simple adhesion. PNH RBC that were exposed to HDL, RBC eluate preparations, or microvesicles demonstrated decreased in vitro complement-mediated hemolysis in the Ham test. Transfer of GPI-linked proteins from soluble preparations containing CD55 and CD59 to PNH erythrocytes is feasible and may have clinical utility.

CD55 Antigens↗

Closing the distance.

Geriatric technicians work in the field, providing a link between care providers and rural elderly patients. In this study, the new role enhanced patient outcomes and satisfaction.

Aged↗

A multicenter study to evaluate a novel assay for quantitation of soluble interleukin 2 receptor in renal transplant recipients.

The clinical utility of monitoring soluble interleukin 2 receptor (sIL-2R) as an indicator of immune stimulation in renal transplant patients was evaluated in a retrospective study at 3 centers. Serum samples (n = 2360) were obtained from 86 (17 living related donor, 69 cadaver) transplant recipients. The patients had received either triple therapy (n = 35) or antilymphocyte antibody induction therapy followed by triple therapy (n = 51). The mean period of postoperative observation was 118 days (range, 6-349 days). Serum sIL-2R concentrations were quantitated by an automated microparticle enzyme immunoassay (MEIA) (Abbott Diagnostics) in which sIL-2R was captured by 7G7/B6 monoclonal antibody-coated microparticles and detected by an immunospecific rabbit antihuman sIL-2R-alkaline phosphatase conjugate. A distinct advantage of the technique was rapid turn-around time: 1-24 results were obtained in less than 50 min. Cyclosporine trough concentrations were determined by radioimmunoassay or high-performance liquid chromatography. Diagnosis of rejection was established by clinical and histological criteria. The mean sIL-2R concentration in patients receiving antilymphocyte antibody induction therapy increased from 3486 +/- 1729 U/ml (+/- SD) at the time of transplant to a maximum of 7395 +/- 7101 U/ml on the third day posttransplant; this increase was not observed in patients receiving triple therapy (P less than 0.0001). By the sixth day of posttransplant, there were no differences in sIL-2R levels in the two groups. Fifty rejection episodes were observed in 29 patients on triple therapy. The mean sIL-2R concentration rose from 3022 U/ml at the data point prior to rejection to 3524 U/ml at the time of rejection. Thirty-four rejection episodes were observed in 26 patients receiving induction therapy. The mean sIL-2R concentration was 3015 U/ml at the data point prior to rejection and 4815 U/ml at the time of rejection. The sIL-2R concentrations began increasing earlier and rose higher in rejecting patients who received induction therapy than in those receiving triple therapy. Early posttransplant sIL-2R levels increased significantly more in cadaver recipients than in LRD recipients, reaching a maximum on day 2 posttransplant (P less than 0.001). Prerejection sIL-2R concentrations were significantly lower in LRD recipients than in cadaver recipients (2248 U/ml vs. 4290 U/ml, P less than 0.02), as were sIL-2R levels at the time of diagnosis of rejection (2800 U/ml vs. 4832 U/ml, P = 0.01). The mean sIL-2R level in stable long-term graft recipients was 2110 U/ml, with approximately 90% of values less than 3000 U/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Prevention and control of infection.

Foal septicemia is a major cause of neonatal morbidity and mortality. In order to improve success rates, earlier diagnosis and treatment are essential. This article stresses methods to prevent and treat infections in the compromised equine neonate.

Animals↗

Deaths associated with warfarin in elderly patients.

The four cases presented illustrate fatal errors in the management of elderly patients at different stages in the chain of their anticoagulation treatment. As indications for anticoagulation increase in the elderly, more care needs to be taken.

Aged↗