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Biomedical subjects

D E Anderson

Publications and source records attributed to D E Anderson.

At least 19 recordsLinked to original sources

Comparison of antibody- and cell-mediated immune responses after intramuscular hepatitis C immunizations of BALB/c mice.

Current treatments for hepatitis C infection have limited efficacy, and there is no vaccine available. The goal of this study was to compare the immune response to several immunization combinations against hepatitis C virus (HCV). Six groups of mice were immunized at weeks 0, 4, and 8 with different combinations of a candidate HCV vaccine consisting of 100 microg recombinant HCV core/E1/E2 (rHCV) DNA plasmid and/or 25 microg rHCV polyprotein and 50 microL Montanide ISA- 51. Four weeks after the last injection, all groups of mice were sacrificed and blood samples and spleens were collected for measuring the levels of specific HCV antibodies (total IgG, IgG1, and IgG2a). Cell proliferation and intracellular interferon-gamma were also measured. Among the groups of immunized mice, only the mice immunized with rHCV DNA plasmid, rHCV polyprotein, and montanide (group D) and mice immunized with rHCV polyprotein and montanide (group F) demonstrated a significant increase in the total IgG titer after immunization. IgG1 was the predominant antibody detected in both groups D and F. No IgG2a was detected in any of the groups. Proliferation assays demonstrated that splenocytes from group D and group C (rHCV DNA primed/rHCV polyprotein boost) developed significant anti-HCV proliferative responses. The combination of an rHCV DNA plasmid, rHCV polyprotein, and montanide induced a high antibody titer with a predominance of IgG1 antibodies and recognized the major neutralization epitopes in HVR1. In contrast, group C did not show an increase in anti-HCV antibodies, but did show a proliferative response.

Adjuvants, Immunologic↗

An unaddressed issue of agricultural terrorism: a case study on feed security.

In the late winter of 2003, a number of livestock animals in the Midwest were poisoned due the accidental contamination of a popular commercial feed with a lethal additive. Although all the evidence indicates this incident had no malicious or terrorist intent, it is informative as a case study highlighting potential security implications with respect to a terrorist event directed at U.S. agriculture.

Agriculture↗

Polyflex stent: is it radiopaque enough?

We report a case of tracheal stenosis in which a migrated Polyflex (Rusch AG, Germany) stent entered the right main bronchus but could not be identified on the chest radiograph. The stent was identified at bronchoscopy and removed under general anaesthesia. Polyflex stents are radiopaque but may not always show up on radiograph. We recommend reliance on clinical symptoms rather than imaging to diagnose migration. If stent migration is suspected then imaging should include thoracic inlet films that incorporate a lateral view.

Bronchi↗

Immunological memory: contribution of memory B cells expressing costimulatory molecules in the resting state.

Traditionally, emphasis has been placed on the roles of Th cells in generating and amplifying both cellular and humoral memory responses. Little is known about the potential contributions of B cell subsets to immunological memory. Resting memory B cells have generally been regarded as poor APC, attributed in part to the relative paucity of costimulatory molecules identified on their surface. We describe a novel subpopulation of human memory B cells that express CD80 in their resting state, are poised to secrete particularly large amounts of class switched Igs, and can efficiently present Ag to and activate T cells. This functionally distinct B cell subset may represent an important mechanism by which quiescent human B cells can initiate and propagate rapid and vigorous immune memory responses. Finally, these studies extend recent observations in the murine system and highlight the phenotypic and functional diversity that exists within the human B cell memory compartment.

Antigen Presentation↗

Unusual molecular architecture of the Yersinia pestis cytotoxin YopM: a leucine-rich repeat protein with the shortest repeating unit.

Many Gram-negative bacterial pathogens employ a contact-dependent (type III) secretion system to deliver effector proteins into the cytosol of animal or plant cells. Collectively, these effectors enable the bacteria to evade the immune response of the infected organism by modulating host-cell functions. YopM, a member of the leucine-rich repeat protein superfamily, is an effector produced by the bubonic plague bacterium, Yersinia pestis, that is essential for virulence. Here, we report crystal structures of YopM at 2.4 and 2.1 A resolution. Among all leucine-rich repeat family members whose atomic coordinates have been reported, the repeating unit of YopM has the least canonical secondary structure. In both crystals, four YopM monomers form a hollow cylinder with an inner diameter of 35 A. The domain that targets YopM for translocation into eukaryotic cells adopts a well-ordered, alpha-helical conformation that packs tightly against the proximal leucine-rich repeat module. A similar alpha-helical domain can be identified in virulence-associated leucine-rich repeat proteins produced by Salmonella typhimurium and Shigella flexneri, and in the conceptual translation products of several open reading frames in Y. pestis.

Amino Acid Sequence↗

Structure of the Rad50 x Mre11 DNA repair complex from Saccharomyces cerevisiae by electron microscopy.

The RAD50 gene of Saccharomyces cerevisiae is one of several genes required for recombinational repair of double-strand DNA breaks during vegetative growth and for initiation of meiotic recombination. Rad50 forms a complex with two other proteins, Mre11 and Xrs2, and this complex is involved in double-strand break formation and processing. Rad50 has limited sequence homology to the structural maintenance of chromosomes (SMC) family of proteins and shares the same domain structure as SMCs: N- and C-terminal globular domains separated by two long coiled-coils. However, a notable difference is the much smaller non-coil hinge region between the two coiled-coils. We report here a structural analysis of full-length S. cerevisiae Rad50, alone and in a complex with yeast Mre11 by electron microscopy. Our results confirm that yeast Rad50 does have the same antiparallel coiled-coil structure as SMC proteins, but with no detectable globular hinge domain. However, the molecule is still able to bend sharply in the middle to bring the two catalytic domains together, indicating that the small hinge domain is flexible. We also demonstrate that Mre11 binds as a dimer between the catalytic domains of Rad50, bringing the nuclease activities of Mre11 in close proximity to the ATPase and DNA binding activities of Rad50.

DNA↗

Bimodal activation of SMC ATPase by intra- and inter-molecular interactions.

Structural maintenance of chromosomes (SMC) proteins play fundamental roles in higher-order chromosome dynamics from bacteria to humans. It has been proposed that the Bacillus subtilis SMC (BsSMC) homodimer is composed of two anti-parallel coiled-coil arms, each having an ATP-binding domain at its distal end. It remains totally unknown, however, how the two-armed structure supports ATP-dependent actions of BsSMC. By constructing a number of mutant derivatives including 'single-armed' BsSMC, we show here that the central hinge domain provides a structural flexibility that allows opening and closing of the two arms. This unique structure brings about bimodal regulation of the SMC ATPase cycle. Closing the arm can trigger ATP hydrolysis by allowing an end-end interaction within a dimer (intramolecular mode). When bound to DNA, ATP promotes a dimer-dimer interaction, which in turn activates their DNA-dependent ATPase activity (intermolecular mode). Our results reveal a novel mechanism of ATPase regulation and provide mechanistic insights into how eukaryotic SMC protein complexes could mediate diverse chromosomal functions, such as chromosome condensation and sister chromatid cohesion.

Adenosine Triphosphatases↗

Structural basis for oligosaccharide recognition by Pyrococcus furiosus maltodextrin-binding protein.

A maltodextrin-binding protein from Pyrococcus furiosus (PfuMBP) has been overproduced in Escherichia coli, purified, and crystallized. The crystal structure of the protein bound to an oligosaccharide ligand was determined to 1.85 A resolution. The fold of PfuMBP is very similar to that of the orthologous MBP from E. coli (EcoMBP), despite the moderate level of sequence identity between the two proteins (27 % identity, 46 % similarity). PfuMBP is extremely resistant to heat and chemical denaturation, which may be attributed to a number of factors, such as a tightly packed hydrophobic core, clusters of isoleucine residues, salt-bridges, and the presence of proline residues in key positions. Surprisingly, an attempt to crystallize the complex of PfuMBP with maltose resulted in a structure that contained maltotriose in the ligand-binding site. The structure of the complex suggests that there is a considerable energy gain upon binding of maltotriose in comparison to maltose. Moreover, isothermal titration calorimetry experiments demonstrated that the binding of maltotriose to the protein is exothermic and tight, whereas no thermal effect was observed upon addition of maltose at three temperatures. Therefore, PfuMBP evidently is designed to bind oligosaccharides composed of three or more glucopyranose units.

Amino Acid Sequence↗

Propylene glycol toxicosis in a llama.

Propylene glycol toxicosis in llamas can result from overzealous administration of propylene glycol-containing gels formulated and labeled for use in cattle. Treatment of ketosis in llamas requires re-establishment of stomach flora and stimulation of appetite.

3-Hydroxybutyric Acid↗

Overcoming original (antigenic) sin.

Original antigenic sin describes a phenomenon in which the antibody response elicited in an individual after a secondary viral infection reacts more strongly to the viral variant that originally infected the individual. As T helper cells play critical roles in promoting antibody responses, a similar phenomenon may hold true for T helper cell responses. This concept is particularly relevant to the development of vaccines against viruses such as human immunodeficiency virus and hepatitis C virus, in which myriad viral variants are present throughout the human population. We have compared the effects of priming the immune system with a single peptide epitope or with a cocktail of related peptides based on the epitope. Our data demonstrate that immunization with multiple peptide variants expands a more broadly reactive and durable T helper cell response than does immunization with a single peptide. This vaccine strategy may circumvent original antigenic sin.

AIDS Vaccines↗

The flip side of perception-action coupling: locomotor experience and the ontogeny of visual-postural coupling.

The possible role of motor development on psychological function is once again a topic of great theoretical and practical importance. The revival of this issue has stemmed from a different approach to the topic, away from Gesell's interest in the long-term prediction of psychological functions from early motoric assessments, toward an attempt to understand how the acquisition of motor skills orchestrates psychological changes. This paper describes how the acquisition of one motor skill, prone locomotion, has been linked to developmental changes in an infant's ability to regulate posture based on information available in patterns of optic flow. It is argued that the onset of prone locomotion presses the infant to differentiate spatially delimited regions of optic flow to effectively and efficiently control the important subtasks nested within the larger task of locomotion, namely, steering, attending to the surface of support, and maintaining postural control. Following this argument, a research program is described that aims to determine if locomotor experience is causally linked to improvements in the ability to functionalize peripheral optic flow for postural control or whether locomotor experience is merely a maturational forecaster of such improvements. Finally, a hypothesis is put forward that links the emergence of wariness of heights to infants' ability to regulate posture on the basis of peripheral optic flow. The paper's overarching theoretical point is the principle of probabilistic epigenesis, which states that one developmental acquisition produces experiences that bring about a host of new developmental changes in the same and different domains.

Humans↗

Anatomy of the distal limb.

A detailed knowledge of anatomy is essential to understand the various pathologic processes and to perform different surgical techniques involving the limbs of cattle. This article reviews macroscopic anatomy of the distal limb, muscle-tendon units, neurovascular anatomy, and external and microanatomy of the claw.

Animals↗

Lameness examination in cattle.

Veterinarians are often asked to examine cattle for lameness. A good history, observation of stance and stride, and physical examination are critical to the diagnosis of lameness in cattle. Methods of examination, including observation of the animal at a distance and during movement, are described. Lameness grading systems and ancillary diagnostic tests are also discussed.

Animals↗

Surgical treatment of lameness.

Digital diseases are commonly seen in cattle. Cattle affected by digital disorders do not always respond to conservative therapy and require surgery. Surgical procedures for the common digital disorders are described, with emphasis on the different approaches to the distal interphalangeal joint.

Amputation, Surgical↗

Prevention of lameness in cow-calf operations.

Lameness is a significant cause of economic loss, premature culling, and loss of genetics in cow-calf operations. In recent years, attention to treatment and prevention of lameness has increased. Veterinarians must be aware of factors associated with lameness such as genetics, environment, and nutrition so that preventive measures can be instituted in consultation with ranchers.

Animal Husbandry↗

Racial differences in resting end-tidal CO2 and circulating sodium pump inhibitor.

Previous studies have shown that high end-tidal CO2 (PetCO2) is a marker for sodium sensitivity of blood pressure (BP) in White Americans, and that the BP of African Americans is more sensitive to high sodium intake than that of whites. The present study tested the hypothesis that resting PetCO2 is higher in normotensive African Americans than in whites. Resting end-tidal CO2 of 395 white and 125 African American participants in the Baltimore Longitudinal Study on Aging was monitored for 20 min with a respiratory gas monitor, and BP and heart rate were recorded every 5 min by oscillometric methodology. Twenty-four-hour urinary excretion of a circulating sodium pump inhibitor marinobufagenin-like compound (MBG), which increases when plasma volume is expanded, was also analyzed by fluoroimmunoassay in racial groups. Mean resting PetCO2 of African American men was higher than that of white men (38.1+/-0.5 v 36.4+/-0.3 mm Hg), and resting PetCO2 of African American women was higher than that of white women (37.7+/-0.3 v 36.2+/-0.3 mm Hg). The differences were not significant in either men or women less than 50 years old, but were substantial in both men and women more than 50 years. Twenty-four-hour urinary excretion of MBG was higher in white (2.7+/-0.2 pmol) than in African American (2.1+/-0.2 pmol) participants, and high PetCO2 was a significant independent predictor of high MBG excretion in African Americans. These data are consistent with the hypothesis that the higher resting PetCO2 in African Americans plays a role in slower urinary excretion of sodium, greater BP sensitivity to high sodium intake, and increased prevalence of chronic hypertension.

Age Distribution↗

Molecular targets for nutrients involved with cancer prevention.

Dietary nutrients can influence cancer risk by inhibiting or enhancing carcinogenesis through diverse mechanisms of action. The identification and elucidation of their sites of action have been a focus of nutrition and cancer research for more than four decades. Transforming nutrition and cancer research from a predominantly observational to a molecular approach offers exciting opportunities for truly identifying those who will and will not benefit from dietary intervention strategies. The emerging field of nutritional genomics, defined here as the study of any genetic or epigenetic interaction with a nutrient, will be key to this evolution. Unraveling which genetic upregulation or downregulation leads to subsequent phenotype changes will not be easy. There is evidence that genetic polymorphisms can influence the dynamics between nutrients and molecular targets and, thus, contribute to variation in response among individuals. Because many molecular targets will likely be identified, it may be necessary to credential nutrients, that is, to determine which specific nutrient-related genetic and epigenetic changes bring about phenotypic changes, to establish which interactions are the most important and under what circumstances. Vitamin D, calcium, folate, selenium, genistein, and resveratrol are highlighted, because they represent specific classes of nutrients and illustrate the need to credential various nutrients to understand their physiological significance in cancer prevention. As the science of nutrition unfolds, a clearer understanding will emerge about how nutrients can modulate cancer risk through molecular interactions and how foods might be changed by agronomic approaches and/or biotechnology. Undeniably, embracing new genomic technologies offers exciting opportunities for advances in the broad area of nutrition, especially those related to cancer prevention.

Anticarcinogenic Agents↗