Long-term complications in classic galactosemia are not progressive.

Classic galactosemia (CG) is a potentially lethal genetic disorder that results from profound deficiency of galactose-1-P uridylyltransferase. Despite early detection and life-long dietary restriction of galactose, which is the current standard of care, many patients with CG grow to experience a range of long-term developmental complications that can include difficulties with speech/voice/language, cognitive, motor, and psychosocial outcomes, among other problems. That these complications are common in CG is well-documented, but whether they are also progressive has been a point of controversy for decades.

Long-term effects of a toddler-focused caries prevention programme among Northwestern US tribal children: The TOTS-to-Tweens study.

Objectives: We sought to determine whether American Indian tribe-based interventions that successfully prevented toddler dental caries in a 2005 cohort study (the Toddler Overweight and Tooth Decay Prevention Study, or TOTS) influenced the prevalence of dental caries in children ages 11 to 13 in the same communities ten years later (the TOTS-to-Tweens study).

Methods: We recruited original TOTS participants and conducted school- and community-based dental screenings at tribal communities that received family plus community-wide interventions (F + CW), community interventions only (CW) or were control communities. We also enrolled children who did not participate in TOTS, but were exposed to CW interventions or to the control environment.

Marginal Zone B Cells Induce Alloantibody Formation Following RBC Transfusion.

Red blood cell (RBC) alloimmunization represents a significant immunological challenge for some patients. While a variety of immune constituents likely contribute to the initiation and orchestration of alloantibodies to RBC antigens, identification of key immune factors that initiate alloantibody formation may aid in the development of a therapeutic modality to minimize or prevent this process. To define the immune factors that may be important in driving alloimmunization to an RBC antigen, we determined the specific immune compartment and distinct cells that may initially engage transfused RBCs and facilitate subsequent alloimmunization.

Complement serves as a switch between CD4+ T cell-independent and -dependent RBC antibody responses.

RBC alloimmunization represents a significant immunological challenge for patients requiring lifelong transfusion support. The majority of clinically relevant non-ABO(H) blood group antigens have been thought to drive antibody formation through T cell-dependent immune pathways. Thus, we initially sought to define the role of CD4+ T cells in formation of alloantibodies to KEL, one of the leading causes of hemolytic transfusion reactions.

Antigen Density Dictates Immune Responsiveness following Red Blood Cell Transfusion.

Although RBC transfusion can result in the development of anti-RBC alloantibodies that increase the probability of life-threatening hemolytic transfusion reactions, not all patients generate anti-RBC alloantibodies. However, the factors that regulate immune responsiveness to RBC transfusion remain incompletely understood. One variable that may influence alloantibody formation is RBC alloantigen density.

Riboflavin-ultraviolet light pathogen reduction treatment does not impact the immunogenicity of murine red blood cells.

Background: Ultraviolet (UV) illumination/pathogen reduction effectively inactivates white blood cells (WBCs) in whole blood. Given that cotransfused WBCs may impact recipient immune responses, we hypothesized that pathogen reduction of whole blood may alter responses to RBC antigens.

Study Design And Methods: Transgenic mice expressing a model (HOD) antigen, authentic human (hGPA or KEL) antigens, or natural fluorescence (uGFP) on their RBCs were utilized as blood donors.

Antigen modulation confers protection to red blood cells from antibody through Fcγ receptor ligation.

Autoantibodies and alloantibodies can damage self-tissue or transplanted tissues through either fixation of complement or ligation of FcγRs. Several pathways have been described that imbue self-tissues with resistance to damage from complement fixation, as a protective measure against damage from these Abs. However, it has been unclear whether parallel pathways exist to provide protection from FcγR ligation by bound Abs.

A novel role for C3 in antibody-induced red blood cell clearance and antigen modulation.

Hemolytic transfusion reactions (HTRs) due to incompatible red blood cell (RBC) transfusions are a leading cause of transfusion associated death. Although many transfused incompatible RBCs are cleared, some remain in circulation despite the presence of RBC-specific antibodies, potentially due to "antigen modulation." With a goal of better understanding incompatible RBC clearance, we generated a murine model with RBC-specific expression of a clinically significant human antigen (KEL2) known to be involved in antigen modulation as well as in HTRs.

Alloantibodies to a paternally derived RBC KEL antigen lead to hemolytic disease of the fetus/newborn in a murine model.

Exposure to nonself red blood cell (RBC) antigens, either from transfusion or pregnancy, may result in alloimmunization and incompatible RBC clearance. First described as a pregnancy complication 80 years ago, hemolytic disease of the fetus and newborn (HDFN) is caused by alloimmunization to paternally derived RBC antigens. Despite the morbidity/mortality of HDFN, women at risk for RBC alloimmunization have few therapeutic options.

Addition of ascorbic acid solution to stored murine red blood cells increases posttransfusion recovery and decreases microparticles and alloimmunization.

Background: The storage of red blood cells (RBCs) results in numerous changes, which over time result in decreased recovery of transfused RBCs. In addition (at least in animal models), stored RBCs can be more immunogenic and also stimulate the systemic release of inflammatory cytokines in transfusion recipients. One component of the RBC storage lesion is the accumulation of oxidative damage.

Trends and correlates of child passenger restraint use in 6 Northwest tribes: the Native Children Always Ride Safe (Native CARS) project.

Objectives: We compared proportions of children properly restrained in vehicles in 6 Northwest American Indian tribes in 2003 and 2009, and evaluated risks for improper restraint.

Methods: During spring 2009 we conducted a vehicle observation survey in Oregon, Washington, and Idaho tribal communities. We estimated the proportions of children riding properly restrained and evaluated correlates of improper restraint via log-binomial regression models for clustered data.

Initiation and regulation of complement during hemolytic transfusion reactions.

Hemolytic transfusion reactions represent one of the most common causes of transfusion-related mortality. Although many factors influence hemolytic transfusion reactions, complement activation represents one of the most common features associated with fatality. In this paper we will focus on the role of complement in initiating and regulating hemolytic transfusion reactions and will discuss potential strategies aimed at mitigating or favorably modulating complement during incompatible red blood cell transfusions.

Generation of transgenic mice with antithetical KEL1 and KEL2 human blood group antigens on red blood cells.

Background: KEL1, also known as "K", is one of the most immunogenic red blood cell (RBC) antigens. KEL2, also known as "k," differs from KEL1 by a single amino acid. Anti-Kell system antibodies can lead to significant adverse clinical outcomes in humans, including hemolytic complications in alloimmunized transfusion recipients or in infants of alloimmunized mothers.

Transfusion in the absence of inflammation induces antigen-specific tolerance to murine RBCs.

Most human transfusion recipients fail to make detectable alloantibodies to foreign RBC antigens ("nonresponders"). Herein, we use a murine model to test the hypothesis that nonresponders may be immunologically tolerant. FVB mice transfused with RBCs expressing transgenic human glycophorin A (hGPA) antigen in the absence of inflammation produced undetectable levels of anti-hGPA immunoglobulins, unlike those transfused in the presence of polyinosinic:polycytidylic acid-induced inflammation.

Alloimmunization against RBC or PLT antigens is independent of TRIM21 expression in a murine model.

Generation of alloantibodies to transfused RBCs can be a serious medical problem for patients who require chronic RBC transfusion therapy. Patients with sickle cell disease have a substantially increased rate of alloimmunization compared to other chronically transfused populations. A recent study has forwarded the hypothesis that a polymorphism in an immunoregulatory gene in close proximity to beta-globin (TRIM21 rs660) plays a role in the increased rates of RBC alloimmunization in sickle cell patients.

Restraint use among northwest American Indian children traveling in motor vehicles.

Objectives: We sought to estimate motor vehicle passenger restraint use among Northwest American Indian children 8 years old or younger and to determine factors associated with using proper (i.e., age and weight appropriate) passenger restraint systems.

Causes of visual impairment and common eye problems in Northwest American Indians and Alaska Natives.

Objectives: Little information exists regarding the causes of visual impairment and the most common eye problems in American Indians/Alaska Natives.

Methods: We randomly sampled American Indians/Alaska Natives older than 40 years from 3 tribes within the Northwest region.

Results: We found a higher prevalence of visual impairment and normal-tension glaucoma, as well as a lower prevalence of ocular hypertension, in American Indians/Alaska Natives compared with previous results in other racial/ethnic groups.