Children's Hospital Oakland Research Institute

About: Children's Hospital Oakland Research Institute is a based out in . It is known for research contribution in the topics: Population & Human leukocyte antigen. The organization has 1568 authors who have published 2480 publications receiving 203418 citations.

Microchimerism and tolerance following intrauterine transplantation and transfusion for α-thalassemia-1

Abstract: A fetus homozygous for α-thalassemia-1 was given haploidentical paternal CD34 cells at 13, 19 and 24 weeks’ gestation and supported through pregnancy by blood transfusion. The fetal hematocrit ranged between 27 and 47% and between one half and three quarters of this hemoglobin was of recipient (Bart’s) type. Intrauterine growth proceeded normally and no significant fetal hydrops was detected. Tests for donor HLA antigens, and α-globin DNA, were negative on fetal blood samples drawn before birth. A positive signal for α-globin DNA was obtained from cord blood and from marrow obtained at 3 months of age, suggesting that some donor stem cells had persisted in the recipient. The infant’s blood mononuclear cells showed little proliferative and no cytotoxic response to the donor while responses to a third party were present. Additional paternal CD34 cells given at 3 months age did not reduce transfusion dependency in the subsequent 6 months. Our results show that repeated transfusions can support an α-thalassemia-1 fetus through pregnancy, in this instance without significant birth defects or apparent hypoxic tissue injury. The donor stem cells did not have a survival advantage compared with endogenous stem cells, but appeared to survive in the recipient as judged by the persistence of an α-globin DNA signal. In vitro studies of alloreactivity suggest tolerization of the host to the donor’s MHC disparity. Future efforts will focus on exploiting this tolerance to improve the level of donor chimerism.

Extracellular virulence factors of Streptococcus pneumoniae.

Abstract: Streptococcus pneumoniae is one of the major human bacterial pathogens Current prophylactic agents against this pathogen are limited in their protective abilities and the role of therapeutics has been inadequate as resistant strains emerge The development of new and improved therapies to combat the pneumococcal disease is necessary In order to accomplish this, an understanding of the interactions between this bacterium and the host tissues is essential Such interactions largely involve extracellular virulence factors that are expressed by the pathogen to interact with the host These virulence factors include those based on sugars (glycome-based) as their building blocks, and proteins that are built from amino acids (proteome-based) The first group includes primarily the capsule, teichoic and lipoteichoic acids The second group is diverse and includes numerous surface proteins that are attached to the cell wall of pneumococci utilizing a variety of methods For the purpose of this review these surface proteins were divided into three categories, proteins bound to peptidoglycan, those bound to choline residues present on the surface of penumococci, and those bound to the lipids of the cytoplasmic membrane Both the glycome-based and protein-based virulence factors are described, analyzed, and represented graphically Whenever possible, structural properties of these molecules were introduced

Somatic Hypermutation and Diverse Immunoglobulin Gene Usage in the Human Antibody Response to the Capsular Polysaccharide of Streptococcus pneumoniae Type 6B

Abstract: Combinatorial cloning and expression library analysis were used to determine the expressed human antibody repertoire specific for the capsular polysaccharide (PS) of Streptococcus pneumoniae serotype 6B. Sequence analysis of 55 6B-specific antibody Fab fragments isolated from six vaccinated donors reveal that different individuals used a variety of heavy and light chain germ line variable (V) region genes to form pneumococcal capsular PS (PPS) 6B-specific paratopes. Within each donor, however, the response was more restricted, with five of the six donors using at most one or two gene pairs to form combining sites. Analysis also indicated that although the response in each donor was oligoclonal in terms of variable gene usage, the combination of extensive somatic hypermutation, deletion of germ line-encoded residues, insertion of non-germ line-encoded residues, and intraclonal isotype switching generated a surprising degree of paratope diversity within the individuals analyzed. In contrast to previously studied PS-specific responses, we find that the PPS 6B repertoire makes use of a diverse collection of heavy-chain and light-chain V region gene products to form specific paratopes, with no apparent tendency for conservation of immunoglobulin gene usage between individuals.

Ath-2, a second gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice.

Abstract: Strain C57BL/6J and A/J differ at two genes determining atherosclerosis susceptibility. The first gene, Ath-1, was described earlier and this report characterizes Ath-2. The alleles at Ath-2 are r for resistance and s for susceptibility to atherosclerosis. The resistant phenotype in female mice is characterized by high plasma high density lipoprotein-cholesterol levels (74 mg/dl +/- SEM 2) and very few lesions/mouse after 14 weeks of consumption of an atherogenic diet (0.1 +/- SEM 0.1 in a predetermined region of the aorta). The susceptible phenotype in female mice is characterized by low levels of high density lipoprotein-cholesterol (35 mg/dl +/- SEM 1) and 1.2 lesions/mouse +/- SEM 0.2 in the same region of the aorta. In Ath-2 heterozygotes, resistance is dominant to susceptibility. Recombinant inbred strains derived from C57BL/6 and A were characterized for Apoa 1, Apoa 2 and susceptibility to atherosclerosis. Ath-1 and Ath-2 interact with each other so that resistant alleles at either locus confer a resistant phenotype to the animal. The map position of Ath-2 is not known, but Ath-2 does not map near genes determining the apolipoproteins for A-I, A-II, or E.

LPA Variants Are Associated With Residual Cardiovascular Risk in Patients Receiving Statins.

Abstract: Background: Coronary heart disease (CHD) is a leading cause of death globally. Although therapy with statins decreases circulating levels of low-density lipoprotein cholesterol and the incidence of...