Search

Introduction: Adverse reactions are relatively common during peanut oral immunotherapy. To reduce the risk to the patient, some researchers have proposed modifying the allergen to reduce IgE reactivity, creating a putative hypoallergen. Analysis of recently cloned human IgG from patients treated with peanut immunotherapy suggested that there are three common conformational epitopes for the major peanut allergen Ara h 2. We sought to test if structural information on these epitopes could indicate mutagenesis targets for designing a hypoallergen and evaluated the reduction in IgE binding via immunochemistry and a mouse model of passive cutaneous anaphylaxis (PCA)., Methods: X-ray crystallography characterized the conformational epitopes in detail, followed by mutational analysis of key residues to modify monoclonal antibody (mAb) and serum IgE binding, assessed by ELISA and biolayer interferometry. A designed Ara h 2 hypoallergen was tested for reduced vascularization in mouse PCA experiments using pooled peanut allergic patient serum., Results: A ternary crystal structure of Ara h 2 in complex with patient antibodies 13T1 and 13T5 was determined. Site-specific mutants were designed that reduced 13T1, 13T5, and 22S1 mAbs binding by orders of magnitude. By combining designed mutations from the three major conformational bins, a hexamutant (Ara h 2 E46R, E89R, E97R, E114R, Q146A, R147E) was created that reduced IgE binding in serum from allergic patients. Further, in the PCA model where mice were primed with peanut allergic patient serum, reactivity upon allergen challenge was significantly decreased using the hexamutant., Conclusion: These studies demonstrate that prior knowledge of common conformational epitopes can be used to engineer reduced IgE reactivity, an important first step in hypoallergen design., (© 2024 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Evidence for inequitable advancement and salary disparity for women in academia is compelling, but only a marginal amount of research has explored this in the field of Marriage and Family Therapy (MFT) specifically. Current research provides preliminary evidence that women remain underrepresented at the Full Professor rank and are paid less than men MFT faculty. This study collected publicly available data for MFT faculty in public universities to explore gender differences in advancement between ranks, salary disparity, and the representation of women and men in the highest and lowest paying niches of MFT academia. Results showed that, despite being 60.15% of MFTs in public universities, women were paid an average of $5596.25 less than men. Men were 1.40 times more likely than women to be promoted to Full Professor on time-within 13 years of their terminal degree. Implications for addressing inequitable advancement and salary disparity for women MFT faculty are discussed., (© 2022 American Association for Marriage and Family Therapy.)

Learning to sequence movements is necessary for skillful interaction with the environment. Neuroplasticity, particularly long-term potentiation (LTP), within sensorimotor networks underlies the acquisition of motor skill. Short-term immobilization of the arm, even less than 12 hours, can reduce corticospinal excitability and increase the capacity for LTP-like plasticity within the contralateral primary motor cortex. However, it is still unclear whether short-term immobilization influences motor skill acquisition. The current study aimed to evaluate the effect of short-term arm immobilization on implicit, sequence-specific motor skill acquisition using a modified Serial Reaction Time Task (SRTT). Twenty young, neurotypical adults underwent a single SRTT training session after six hours of immobilization of the non-dominant arm or an equivalent period of no immobilization. Our results demonstrated that participants improved SRTT performance overall after training, but there was no evidence of an effect of immobilization prior to task training on performance improvement. Further, improvements on the SRTT were not sequence-specific. Taken together, motor skill acquisition for sequential, individuated finger movements improved following training but the effect of six hours of immobilization was difficult to discern., Competing Interests: The authors have declared that no competing interests exist.

Previous research has suggested that short-term immobilization of the arm may be a low-cost, non-invasive strategy to enhance the capacity for long-term potentiation (LTP)-like plasticity in primary motor cortex (M1). Short-term immobilization reduces corticospinal excitability (CSE) in the contralateral M1, and interhemispheric inhibition (IHI) from ipsi- onto contralateral M1 is increased. However, it is unclear whether reduced CSE and increased IHI are associated with changes in intracortical inhibition, which has been shown to be important for regulating neuroplasticity in M1. The current study used transcranial magnetic stimulation to evaluate the effects of short-term (6 h) arm immobilization on CSE, IHI, and intracortical inhibition measured bilaterally in 43 neurotypical young adults (23 immobilized). We replicated previous findings demonstrating that immobilization decreased CSE in, and increased IHI onto, the immobilized hemisphere, but a significant change in intracortical inhibition was not observed at the group level. Across individuals, decreased CSE was associated with a decreased short-interval intracortical inhibition, an index of GABA A -ergic inhibition, within the immobilized hemisphere only in the immobilization group. Previous research has demonstrated that decreases in GABA A -ergic inhibition are necessary for the induction of LTP-like plasticity in M1; therefore, decreased intracortical inhibition after short-term arm immobilization may provide a novel mechanism to enhance the capacity for LTP-like plasticity within M1 and may be a potential target for strategies to augment plasticity capacity to enhance motor learning in health and disease., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

This study explored how individual- and community-based resilience factors operated together in order to reduce risk of suicide for a sample of transgender therapy clients. We collected cross-sectional survey data from 106 transgender therapy clients at a local community center, including demographic information, experiences of relational support, participants' emotional stability, and risk for suicide. Results from our mediation analysis indicated that high levels of perceived relational support are related to reduced risk for suicide and that this happens by way of a person's emotional stability. Clinical implications for family therapists are discussed based on the significant indirect effect found in this study., (© 2019 Family Process Institute.)

Background: Small, basic peanut proteins are often poorly extracted in pH-neutral buffers that are optimal for the extraction of peanut storage proteins such as Ara h 1. As a result, such proteins are easily missed as potential allergens., Objective: To analyse the allergenic composition of the basic peanut protein (BPP) fraction., Methods: A peanut extract prepared at pH 4 was fractionated by physicochemical procedures. Chemical analysis was performed by SDS-PAGE and mass spectrometry. Because immunoblotting was found to be inefficient for most of these small basic proteins, IgE-binding activity was measured by coupling the fractions to CNBr-activated Sepharose, followed by incubation with sera from 55 Dutch peanut-allergic children and 125 I-labelled anti-IgE., Results: Most IgE reactivity of the BPP fraction was due to the 5-7 kDa amino-terminal fragment of Ara h 1. This finding was confirmed by the use of the fragment in recombinant form, to which 25/55 of the sera was IgE-positive., Conclusion: The amino-terminal fragment of Ara h 1, a member of a family of small anti-microbial proteins, is an allergen independent of the carboxy-terminal fragment of Ara h 1., (© 2019 John Wiley & Sons Ltd.)

Integration of sensory and motor information is one-step, among others, that underlies the successful production of goal-directed hand movements necessary for interacting with our environment. Disruption of sensorimotor integration is prevalent in many neurologic disorders, including stroke. In most stroke survivors, persistent paresis of the hand reduces function and overall quality of life. Current rehabilitative methods are based on neuroplastic principles to promote motor learning that focuses on regaining motor function lost due to paresis, but the sensory contributions to motor control and learning are often overlooked and currently understudied. There is a need to evaluate and understand the contribution of both sensory and motor function in the rehabilitation of skilled hand movements after stroke. Here, we will highlight the importance of integration of sensory and motor information to produce skilled hand movements in healthy individuals and individuals after stroke. We will then discuss how compromised sensorimotor integration influences relearning of skilled hand movements after stroke. Finally, we will propose an approach to target sensorimotor integration through manipulation of sensory input and motor output that may have therapeutic implications.

Middle school youth (N = 1472) in Central Indiana completed a survey about parent-adolescent sexual communication. Being older, female, mixed race, ever had sex, ever arrested, and higher HIV knowledge were associated with more frequent sexual communication., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Mast cells are well established as divergent modulators of inflammation and immunosuppression, but their role in inflammatory bowel disease (IBD) remains to be fully defined. While previous studies have demonstrated a proinflammatory role for mast cells in acute models of chemical colitis, more recent investigations have shown that mast cell deficiency can exacerbate inflammation in spontaneous colitis models, thus suggesting a potential anti-inflammatory role of mast cells in IBD. Here, we tested the hypothesis that in chronic, spontaneous colitis, mast cells are protective. We compared colitis and intestinal barrier function in IL10 -/- mice to mast cell deficient/IL10 -/- (double knockout (DKO): Kit Wsh/Wsh  × IL10 -/- ) mice. Compared with IL10 -/- mice, DKO mice exhibited more severe colitis as assessed by increased colitis scores, mucosal hypertrophy, intestinal permeability, and colonic cytokine production. PCR array analyses demonstrated enhanced expression of numerous cytokine and chemokine genes and downregulation of anti-inflammatory genes (e.g., Tgfb2 , Bmp2 , Bmp4 , Bmp6 , and Bmp7 ) in the colonic mucosa of DKO mice. Systemic reconstitution of DKO mice with bone marrow-derived mast cells resulted in significant amelioration of IL10 -/- -mediated colitis and intestinal barrier injury. Together, the results presented here demonstrate that mast cells exert anti-inflammatory properties in an established model of chronic, spontaneous IBD. Given the previously established proinflammatory role of mast cells in acute chemical colitis models, the present findings provide new insight into the divergent roles of mast cells in modulating inflammation during different stages of colitis. Further investigation of the mechanism of the anti-inflammatory role of the mast cells may elucidate novel therapies.

Background: Early life adversity (ELA) is a risk factor for development of gastrointestinal disorders later in life. The underlying mechanisms through which ELA and sex interact to influence disease susceptibility remains poorly understood., Methods: Utilizing a porcine early weaning stress (EWS) model to mimic ELA, we investigated the long-term effects of EWS on functional diarrhea, ileal permeability, mast cell activity and mast cell relationship with enteric ganglia., Key Results: Juvenile and adult EWS pigs exhibited chronic, functional diarrhea (EWS 43.6% vs late wean control(LWC) 4.8%, P<.0001), increased intestinal permeability (2 fold increase EWS vs LWC, P<.0001), and mast cell numbers (at 7 weeks and 20 weeks ~1.6 fold increase EWS vs LWC, P<.05). Compared with EWS male castrates (Male-C), females EWS pigs exhibited more frequent diarrhea (58.8% vs 29.9%, P=.0016), and increased intestinal permeability (1-2 fold higher in EWS females, P<.001). Increased mast cell numbers and their enhanced co-localization with neuronal ganglia were observed in both Male-C and female EWS pigs; however, female pigs exhibited greater release of mast cell tryptase upon activation with c48/80 (~1.5 fold increase, P<.05), compared with Male-C pigs., Conclusions and Inferences: These data demonstrate that pigs exposed to ELA exhibit increased vulnerability to functional diarrhea, intestinal permeability and mast cell activity. Further, these studies also showed that EWS female and Male-C pigs exhibited dimorphic responses to EWS with female piglets exhibited greater susceptibility and severity of diarrhea, intestinal permeability and mast cell tryptase release. Together, these findings mimic some of the key pathophysiologic findings in human functional GI disorders functional gastrointestinal disorders (FGIDs) suggesting that the EWS porcine model could be a valuable preclinical translational model for FGID research associated with ELA., (© 2017 John Wiley & Sons Ltd.)

Background: Early life adversity (ELA) is a risk factor for the later-life onset of gastrointestinal (GI) diseases such as irritable bowel syndrome (IBS); however, the mechanisms are poorly understood. Here, we utilized a porcine model of ELA, early weaning stress (EWS), to investigate the influence of ELA on the development and function of the enteric nervous system (ENS)., Methods: Female and castrated male (Male-C) piglets were weaned from their sow either at 15 days of age (EWS) or 28 days of age (late weaning control, LWC). At 60 and 170 days of age, ileal mucosa-submucosa preparations were mounted in Ussing chambers and veratridine- and corticotropin releasing factor (CRF)-releasing factor-evoked short circuit current (Isc ) responses were recorded as indices of secretomotor neuron function. Enteric neuron numbers and the expression of select neurotransmitters and their receptors were also measured., Key Results: Compared with LWC pigs, female, but not Male-C EWS, pigs exhibited heightened veratridine-induced Isc responses at 60 and 170 days of age that were inhibited with tetrodotoxin and atropine. Ileum from EWS pigs had higher numbers of enteric neurons that were choline acetyltransferase positive. Markers of increased cholinergic signaling (increased acetylcholinesterase) and downregulated mucosal muscarinic receptor 3 gene expression were also observed in EWS pigs., Conclusions & Inferences: This study demonstrated that EWS in pigs induces lasting and sex-specific hypersensitivity of secretomotor neuron function and upregulation of the cholinergic ENS. These findings may represent a mechanistic link between ELA and lifelong susceptibility to GI diseases such as IBS., Competing Interests: The authors declare no conflicts of interest., (© 2016 John Wiley & Sons Ltd.)

Background: Der p 23 was recently identified in a European population as a major allergen and potentially a chitin binding protein., Objective: This study sought to assess the importance of Der p 23 among other Dermatophagoides allergens in a North American population and to determine the structure for functional characterization., Methods: IgE binding to Der p 23, Der p 1, Der p 2, Der p 5, Der p 7 and Der p 8 was measured by ELISA. RNA-seq data from D. pteronyssinus were compared as estimates of allergen expression levels. The structure was analysed by X-ray crystallography and NMR., Results: Despite a high prevalence of Der p 23, (75% vs. 87% and 79% for Der p 1 and Der p 2, respectively), the anti-Der p 23 IgE levels were relatively low. The patient response to the 6 allergens tested was variable (n = 47), but on average anti-Der p 1 and anti-Der p 2 together accounted for 85% of the specific IgE. In terms of abundance, the RNA expression level of Der p 23 is the lowest of the major allergens, thirty fold less than Der p 1 and sevenfold less than Der p 2. The structure of Der p 23 is a small, globular protein stabilized by two disulphide bonds, which is structurally related to allergens such as Blo t 12 that contain carbohydrate binding domains that bind chitin. Functional assays failed to confirm chitin binding by Der p 23., Conclusions and Clinical Relevance: Der p 23 accounts for a small percentage of the IgE response to mite allergens, which is dominated by Der p 1 and Der p 2. The prevalence and amount of specific IgE to Der p 23 and Der p 2 are disproportionately high compared to the expression of other Dermatophagoides allergens., (Published 2015. This article is a U.S. Government work and is in the public domain in the USA.)

Background: It is not clear whether cross-reactivity or cosensitization to glutathione S-transferases (GSTs) occurs in tropical and subtropical environments. In the United States, Bla g 5 is the most important GST allergen and lack of coexposure to GSTs from certain species allows a better assessment of cross-reactivity., Objectives: To examine the molecular structure of GST allergens from cockroach (Bla g 5), dust mites (Der p 8 and Blo t 8), and helminth (Asc s 13) for potential cross-reactive sites, and to assess the IgE cross-reactivity of sensitized patients from a temperate climate for these allergens for molecular diagnostic purposes., Methods: Four crystal structures were determined. Sera from patients allergic to cockroach and mite were tested for IgE reactivity to these GSTs. A panel of 6 murine anti-Bla g 5 mAb was assessed for cross-reactivity with the other 3 GSTs using antibody binding assays., Results: Comparisons of the allergen structures, formed by 2-domain monomers that dimerize, revealed few contiguous regions of similar exposed residues, rendering cross-reactivity unlikely. Accordingly, anti-Bla g 5 or anti-Der p 8 IgE from North American patients did not recognize Der p 8 or Bla g 5, respectively, and neither showed binding to Blo t 8 or Asc s 13. A weaker binding of anti-Bla g 5 IgE to Der p 8 versus Bla g 5 (∼ 100-fold) was observed by inhibition assays, similar to a weak recognition of Der p 8 by anti-Bla g 5 mAb. Patients from tropical Colombia had IgE to all 4 GSTs., Conclusions: The lack of significant IgE cross-reactivity among the 4 GSTs is in agreement with the low shared amino acid identity at the molecular surface. Each GST is needed for accurate molecular diagnosis in different geographic areas., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Mn/Fe-superoxide dismutase (SOD) is a family of enzymes essential for organisms to be able to cope with oxygen. These enzymes bound to their classical metals catalyze the dismutation of the free radical superoxide anion (O2(-)) to H2O2 and molecular oxygen. E. coli has the manganese-dependent SOD A and the iron-dependent SOD B., Methods: Strains of E. coli overexpressing SOD A or SOD B were grown in media with different metal compositions. SODs were purified and their metal content and SOD activity were determined. Those proteins were incubated with H2O2 and assayed for oxidation of Amplex red or o-phenylenediamine, consumption of H2O2, release of iron and protein radical formation. Cell survival was determined in bacteria with MnSOD A or FeSOD A after being challenged with H2O2., Results: We show for the first time that the bacterial manganese-dependent SOD A when bound to iron (FeSOD A) has peroxidase activity. The in vivo formation of the peroxidase FeSOD A was increased when media had higher levels of iron because of a decreased manganese metal incorporation. In comparison to bacteria with MnSOD A, cells with FeSOD A had a higher loss of viability when exposed to H2O2., General Significance: The biological occurrence of this fundamental antioxidant enzyme in an alternative iron-dependent state represents an important source of free radical formation., (Published by Elsevier B.V.)

Increasing evidence supports the concept that early-life environmental influences, including nutrition and stress, have an impact on long-term health outcomes and disease susceptibility. The objective of the present study was to determine whether dietary spray-dried plasma (SDP), fed during the first 2 weeks post-weaning (PW), influences subsequent immunological and intestinal injury responses to Salmonella typhimurium challenge. A total of thirty-two piglets (age 16-17 d) were weaned onto nursery diets containing 0, 2·5 % SDP (fed for 7 d PW) or 5 % SDP (fed for 14 d PW), and were then fed control diets (without SDP), for the remainder of the experiment. At 34 d PW (age 50 d), pigs were challenged with 3 × 10⁹ colony-forming units of S. typhimurium. A control group (non-challenged) that was fed 0 % SDP in the nursery was included. At 2 d post-challenge, the distal ileum was harvested for the measurement of inflammatory, histological and intestinal physiological parameters. S. typhimurium challenge induced elevated ileal histological scores, myeloperoxidase (MPO), IL-8 and TNF, and increased intestinal permeability (indicated by reduced transepithelial voltage (potential difference) and elevated 4 kDa fluorescein isothiocyanate dextran (FD4) flux rates). Compared with S. typhimurium-challenged controls (0 % SDP), pigs fed the 5 % SDP-14 d diet exhibited reduced ileal histological scores, MPO levels, IL-8 levels and FD4 flux rates. Pigs fed the 5 % SDP-14 d nursery diet exhibited increased levels of plasma and ileal TNF-α in response to the challenge, compared with the other treatments. These results indicate that inclusion of SDP in PW diets can have an influence on subsequent immunological and intestinal injury responses induced by later-life S. typhimurium challenge.

Cyclophilin (Cyp) allergens are considered pan-allergens due to frequently reported cross-reactivity. In addition to well studied fungal Cyps, a number of plant Cyps were identified as allergens (e.g. Bet v 7 from birch pollen, Cat r 1 from periwinkle pollen). However, there are conflicting data regarding their antigenic/allergenic cross-reactivity, with no plant Cyp allergen structures available for comparison. Because amino acid residues are fairly conserved between plant and fungal Cyps, it is particularly interesting to check whether they can cross-react. Cat r 1 was identified by immunoblotting using allergic patients' sera followed by N-terminal sequencing. Cat r 1 (∼ 91% sequence identity to Bet v 7) was cloned from a cDNA library and expressed in Escherichia coli. Recombinant Cat r 1 was utilized to confirm peptidyl-prolyl cis-trans-isomerase (PPIase) activity by a PPIase assay and the allergenic property by an IgE-specific immunoblotting and rat basophil leukemia cell (RBL-SX38) mediator release assay. Inhibition-ELISA showed cross-reactive binding of serum IgE from Cat r 1-allergic individuals to fungal allergenic Cyps Asp f 11 and Mala s 6. The molecular structure of Cat r 1 was determined by NMR spectroscopy. The antigenic surface was examined in relation to its plant, animal, and fungal homologues. The structure revealed a typical cyclophilin fold consisting of a compact β-barrel made up of seven anti-parallel β-strands along with two surrounding α-helices. This is the first structure of an allergenic plant Cyp revealing high conservation of the antigenic surface particularly near the PPIase active site, which supports the pronounced cross-reactivity among Cyps from various sources., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Bla g 1 is a major allergen from Blatella germanica and one of the primary allergens used to assess cockroach allergen exposure. The epitope of an anti-Bla g 1 scFv was mapped in order to better understand cross reactivity with other group 1 cockroach allergens and patient IgE epitopes. X-ray crystallography was used to determine the structure of the scFv. The scFv epitope on Bla g 1 was located by alanine scanning site-directed mutagenesis and ELISA. Twenty-six rBla g 1-GST alanine mutants were evaluated for variations in binding to the scFv compared to the wild type allergen. Six mutants showed a significant difference in scFv binding affinity. These mutations clustered to form a discontinuous epitope mainly comprising two helices of Bla g 1. The allergen-scFv complex was modeled based on the results, and the epitope region was found to have low sequence similarity with Per a 1, especially among the residues identified as functionally important for the scFv binding to Bla g 1. Indeed, the scFv failed to bind Per a 1 in American cockroach extract. The scFv was unable to inhibit the binding of IgE antibodies from a highly cockroach allergic patient to Bla g 1. Based on the surface area of Bla g 1 occluded by the scFv, putative regions of patient IgE-Bla g 1 interactions can be inferred. This scFv could be best utilized as a capture antibody in an IgE detection ELISA, or to differentiate Bla g 1 from Per a 1 in environmental exposure assays., (Published by Elsevier Ltd.)

Parents with HIV/AIDS are confronted with unique challenges when discussing HIV-related information with their children. Strategies for navigating these challenges effectively have not been systematically examined. In this study, we conducted in-depth interviews with 76 parents with HIV/AIDS who had children ages 10-18 years. Guided by O'Keefe and Delia's definition of a complex communication situation and Goldsmith's normative approach to interpersonal communication, we examined parents' goals for discussing HIV-related information, factors that made conversations challenging, and instances where these conversational purposes conflicted with one another. Our data reveal the following parent-adolescent communication predicaments: relaying safety information about HIV while minimizing child anxiety, modeling open family communication without damaging one's parental identity, and balancing parent-child relational needs amid living with an unpredictable health condition. Parents also described a variety of strategies for mitigating challenges when discussing HIV-related topics. Strategies parents perceived as effective included reframing HIV as a chronic, manageable illness; keeping talk educational; and embedding HIV-related topics within more general conversations. The theoretical and practical applications of these findings are discussed with regard to their relevance to health communication scholars and HIV care professionals.

Aim: This study investigated how parents living with HIV communicated about HIV prevention with their 10-18 year old children., Methods: Interviews with 76 mothers and fathers were analyzed for (1) their experiences discussing HIV prevention with adolescents, and (2) advice on how to best broach HIV-related topics., Results: Interactive conversations, where both parents and adolescents participated, were regarded as effective. Parents emphasized that adolescents should have a "voice" (be able to voice their concerns) and a "choice" (have a variety of effective prevention strategies to choose from) during HIV-related talks., Discussion: A five step process for interactive communication emerged as a result of these discussions., Implications: Health care professionals can facilitate adolescent sexual health by encouraging parents to actively involve their children in discussions about HIV prevention., Conclusion: Future HIV prevention programs could benefit by providing parents with appropriate tools to foster interactive discussions about sexual health with adolescents.

Background: Recent immunological data demonstrated that dendritic cells preferentially recognize advanced glycation end product (AGE)-modified proteins, upregulate expression of the receptor for AGE (RAGE), and consequently bias the immune response toward allergy., Methods: Peanut extract was characterized by mass spectrometry (MS) to elucidate the specific residues and specific AGE modifications found in raw and roasted peanuts and on rAra h 1 that was artificially glycated by incubation with glucose or xylose. The binding of the RAGE-V1C1 domain to peanut allergens was assessed by PAGE and Western analysis with anti-Ara h 1, 2, and 3 antibodies. IgE binding to rAra h 1 was also assessed using the same methods., Results: AGE modifications were found on Ara h 1 and Ara h 3 in both raw and roasted peanut extract. No AGE modifications were found on Ara h 2. Mass spectrometry and Western blot analysis demonstrated that RAGE binds selectively to Ara h 1 and Ara h 3 derived from peanut extract, whereas the analysis failed to demonstrate Ara h 2 binding to RAGE. rAra h 1 with no AGE modifications did not bind RAGE; however, after AGE modification with xylose, rAra h 1 bound to RAGE., Conclusions: AGE modifications to Ara h 1 and Ara h 3 can be found in both raw and roasted peanuts. Receptor for AGE was demonstrated to selectively interact with AGE-modified rAra h 1. If sensitization to peanut allergens occurs in dendritic cells via RAGE interactions, these cells are likely interacting with modified Ara h 1 and Ara h 3, but not Ara h 2., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Objectives: We examined HIV-infected parents' conversations about HIV prevention with their uninfected children, including what facilitated or hindered communication., Methods: Parents with HIV/AIDS (n = 90) who had children aged 10 to 18 years were recruited for a mixed method study from 2009 to 2010. Interviews assessed facilitators and barriers to discussing HIV prevention. A questionnaire identified the frequency and content of conversations, parental confidence level, and perceived importance of discussing preventive topics., Results: Eighty-one percent of parents reported "sometimes" or "often" communicating about HIV prevention. A subset of parents found these conversations difficult; 44% indicated their desire for support. Facilitators to communication included utilizing support, focusing on the benefits of talking, and having a previous relationship with one's child. Barriers to discussions included fear of negative consequences, living in denial, and lacking a parental role model who discussed safer sex. Parents varied as to how they believed their HIV status affected communication. Those who did not disclose their HIV status to their children reported less frequent communication; self-efficacy partially mediated this relationship., Conclusions: Findings highlighted the need for communication skills training that support HIV-infected parents in their efforts to discuss HIV-related information with adolescents.

Group 5 allergens from house dust mites elicit strong IgE antibody binding in mite-allergic patients. The structure of Der p 5 was determined by x-ray crystallography to better understand the IgE epitopes, to investigate the biologic function in mites, and to compare with the conflicting published Blo t 5 structures, designated 2JMH and 2JRK in the Protein Data Bank. Der p 5 is a three-helical bundle similar to Blo t 5, but the interactions of the helices are more similar to 2JMH than 2JRK. The crystallographic asymmetric unit contains three dimers of Der p 5 that are not exactly alike. Solution scattering techniques were used to assess the multimeric state of Der p 5 in vitro and showed that the predominant state was monomeric, similar to Blo t 5, but larger multimeric species are also present. In the crystal, the formation of the Der p 5 dimer creates a large hydrophobic cavity of approximately 3000 A(3) that could be a ligand-binding site. Many allergens are known to bind hydrophobic ligands, which are thought to stimulate the innate immune system and have adjuvant-like effects on IgE-mediated inflammatory responses.

Human DNA polymerase nu (Pol nu) is a conserved family A DNA polymerase of uncertain biological function. Physical and biochemical characterization aimed at understanding Pol nu function is hindered by the fact that, when over-expressed in Escherichia coli, Pol nu is largely insoluble, and the small amount of soluble protein is difficult to purify. Here we describe the use of high hydrostatic pressure to refold Pol nu from inclusion bodies, in soluble and active form. The refolded Pol nu has properties comparable to those of the small amount of Pol nu that was purified from the soluble fraction. The approach described here may be applicable to other DNA polymerases that are expressed as insoluble inclusion bodies in E. coli., ((c) 2009. Published by Elsevier Inc.)

Background: Sensitization to house dust mite allergens is strongly correlated with asthma. Der p 7 elicits strong IgE antibody and T-cell responses in patients with mite allergy. However, the structure and biological function of this important allergen are unknown. Allergen function might contribute to allergenicity, as shown for the protease activity of group 1 mite allergens and the interaction with the innate immune system by group 2 mite allergens., Objective: We sought to determine the crystal structure of Der p 7 and to investigate its biological function., Methods: X-ray crystallography was used to determine the Der p 7 structure. Nuclear magnetic resonance analysis and biochemical assays were used to examine the binding of Der p 7 to predicted ligands., Results: Der p 7 has an elongated structure, with two 4-stranded antiparallel beta-sheets that wrap around a long C-terminal helix. The fold of Der p 7 is similar to that of LPS-binding protein (LBP), which interacts with Toll-like receptors after binding LPS and other bacterially derived lipid ligands. Nuclear magnetic resonance and biochemical assays indicate that Der p 7 does not bind LPS but binds with weak affinity to the bacterial lipopeptide polymyxin B in the predicted binding site of Der p 7., Conclusions: Der p 7 binds a bacterially derived lipid product, a common feature of some allergens. The finding that the group 7, as well as the group 2, mite allergens are structurally similar to different proteins in the Toll-like receptor pathway further strengthens the connections between dust mites, innate immunity, and allergy., (Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Objectives: To evaluate the reach and effectiveness of a diabetes self-management DVD compared to classroom-based instruction., Methods: A hybrid preference/randomized design was used with participants assigned to Choice v. Randomized and DVD v. Class conditions. One hundred and eighty-nine adults with type 2 diabetes participated. Key outcomes included self-management behaviours, process measures including DVD implementation and hypothesized mediators and clinical risk factors., Results: In the Choice condition, four times as many participants chose the mailed DVD as selected Class-based instruction (38.8 v. 9.4%, p<0.001). At the 6-month follow-up, the DVD produced results generally not significantly different than classroom-based instruction, but a combined Class plus DVD condition did not improve outcomes beyond those produced by the classes alone., Discussion: The DVD appears to have merit as an efficient and appealing alternative to brief classroom-based diabetes education, and the hybrid design is recommended to provide estimates of programme reach.

Controversy continues regarding the safety and efficacy of tissue plasminogen activator (tPA) for stroke outside major centers. We reviewed charts from 1998 to 2004 of 493 patients admitted with TIA or stroke to our small rural hospital. There was a 4% tPA treatment rate with no symptomatic intracranial hemorrhage and zero mortality. IV tPA can be safe and effective in the treatment of acute stroke despite the size of the institution.

Several multiple-probe-across-participants design studies were employed to evaluate the effectiveness of a supplemental tutoring intervention using Read Well (Sprick, Howard, & Fidanque, 1998-2000). In Year 1, we conducted two studies with 7 first-, second-, and third-grade children (1 girl and 6 boys), who were classified as having learning disabilities, having attention-deficit disorder, or being English language learners and were identified by their teachers as poor readers. The results of the two studies indicated that 3 of the 5 children who received Read Well instruction showed improvement in passage fluency. Student performance on other measures of reading and comprehension was varied. Differences in student characteristics and in the amount of Read Well instruction received (2 to 7 weeks) seemed to account for the differences in performance. In Year 2, we implemented the same tutoring intervention for a longer duration (up to 16 weeks) and included 5 children in second and third grades (2 girls and 3 boys) with reading difficulties. Two of these children had previously participated in the Year 1 studies. The results indicated growth in reading, spelling, and comprehension for most children. Overall, the findings from Year 1 and 2 studies indicate the benefits of increased instructional intensity and duration for children who struggle with emerging reading skills.

Introduction: Cortical blindness, a rare form of cyclosporine (CSA) neurotoxicity, has previously been described in only nine bone marrow transplant (BMT) recipients., Methods: Our institution averages 35 allogeneic BMT's per year. In the past year we have seen two women with reversible cortical blindness secondary to CSA toxicity., Results: Age (years) (Case 1; Case 2): 32; 22. Day post-BMT: 41; 50. Peak CSA level (ng/ml): 1159; 632. Both had a history of renal toxicity requiring adjustment of CSA dosage. MRI - both with diffuse while matter changes. EEG - both with moderate to severe generalized slowing. Visual evoked potentials were markedly prolonged in both. Auditory evoked potentials: minimally abnormal; normal. Somatosensory evoked potentials - both normal. Prompt improvement occurred with discontinuation of CSA. Followup neurophysiologic evaluations were normal, however structural changes remained on MRI., Conclusion: As neurophysiologic studies closely follow the clinical status they should be included in the evaluation and followup of CSA neurotoxicity.

Introduction: Cortical blindness, a rare form of cyclosporine (CSA) neurotoxicity, has previously been described in only nine bone marrow transplant (BMT) recipients., Methods: Our institutions averages 35 allogeneic BMT's per year. In the past year we have seen two women with reversible cortical blindness secondary to CSA toxicity., Results: Age (years) (Case 1; Case 2): 32; 22. Day post-BMT: 41: 50. Peak CSA level (ng/ml): 1159; 632. Both had a history of renal toxicity requiring adjustment of CSA dosage. MRI - both with diffuse white matter changes. EEG-both with moderate to severe generalized slowing. Visual evoked potentials were markedly prolonged in both. Auditory evoked potentials: minimally abnormal; normal. Somatosensory evoked potential - both normal. Prompt improvement occurred with discontinuation of CSA. Followup neurophysiologic evaluations were normal, however structural changes remain on MRI., Conclusion: As neurophysiologic studies closely follow the clinical status they should be included in the evaluation and followup of CSA neurotoxicity.

Anorectal dysfunction and constipation are well recognized in Parkinson's disease and may reflect the direct involvement of the gastrointestinal tract by the primary Parkinson's disease process. We hypothesized, therefore, that anorectal function would alter in parallel with fluctuations in motor function related to on- and off-periods in Parkinson's disease, and employed combined anorectal manometry and electromyography to investigate anorectal function during both on- and off-periods in patients with Parkinson's disease. Manometric recordings revealed a deterioration in voluntary sphincter squeeze during off-periods (squeeze index, on versus off, mean +/- SEM: 46.4 +/- 11.1 versus 29.6 +/- 7.9 mm Hg, p < 0.05); correspondingly, simultaneous electromyographic (EMG) recordings showed poor recruitment of external anal sphincter and puborectalis muscles during off-periods. A hypercontractile ("paradoxical") rectosphincteric reflex response occurred during both on- and off-periods, and was associated with an increase in EMG activity in the external sphincter and/or the puborectalis muscle. These changes in manometric and EMG parameters paralleled changes in overall motor function. These findings provide further support for the involvement of the pelvic floor musculature in the Parkinson's disease process and also provide EMG correlates for some of the manometric abnormalities described in Parkinson's disease.

Cervical dystonia, although rare in the general population, can severely affect the lives of those afflicted with the disease. Throughout history several theories have been proposed regarding its etiology and pathophysiology, from underlying mental disorders to post-infectious to altered basal ganglia and brainstem function. However, CD remains poorly understood. Because of its similarity to Idiopathic Torsion Dystonia a genetic basic is suspected, but is not proven. Without a true understanding of the disease treatment remains symptomatic, and begins with physical therapy and medications and progresses to consideration of surgery. These treatment strategies have provided some relief, which is usually less than satisfactory within a short period of time. Recently, the use of botulinum toxin has provided significant symptomatic relief of pain in CD and has been associated with subjective and objective improvement in head posture. This newest therapy, although symptomatic, restores a more normal head posture and pain relief enabling the individuals with CD to continue to be active and productive participants in life, providing a ray of hope to these people as we continue to search for a better understanding of the disease process and the development of more effective treatment strategies.

Unlabelled: Despite the high prevalence of Parkinson's disease, the pathophysiology of its gastrointestinal symptoms remains poorly understood., Objectives: to evaluate swallowing and defecatory function in patients with Parkinson's disease and age- and sex-matched controls and to correlate objective findings with subjective symptoms., Methods: The following studies were performed on 13 patients with Parkinson's disease and seven controls: extrapyramidal function assessment, gastrointestinal symptom survey, videoesophagram, colon transit study, defecography, and anorectal manometry., Results: Abnormal salivation (frequency, %, control vs. Parkinson's disease: 14 vs. 77, p < 0.05), dysphagia (14 vs. 77, p < 0.05), constipation (14 vs. 31, p < 0.05), and defecatory dysfunction (29 vs. 77, p < 0.05) were more common among Parkinsonian patients. However, videoesophagographic abnormalities were equally common in both groups. Colon transit time was significantly prolonged in the Parkinson's disease group. Altered puborectalis function was noted on defecography in 31% of Parkinson's disease subjects, but in none of the controls (p < 0.05). Anorectal manometry identified several abnormalities in the Parkinson's disease group, which included decreased basal anal sphincter pressures, prominent phasic fluctuations on squeeze, and a hyper-contractile external sphincter response to the rectosphincteric reflex. Many patients exhibited both slow transit and manometric abnormalities, and symptoms were poor predictors of test results., Conclusion: In this group of patients with mild to moderate Parkinson's disease, videoesophagographic abnormalities were not confined to the patients with Parkinson's disease. Studies of colonic and anorectal function, in contrast, identified a number of abnormalities. Therefore, colonic and anorectal dysfunction appears to be an early gastrointestinal manifestation of Parkinson's disease, and may represent the direct involvement of the gut by this disease process.

We evaluated the effects of the dopaminergic agent apomorphine on defecation and anorectal function in patients with Parkinson's disease (PD). A gastrointestinal symptom survey, extrapyramidal assessment, defecating proctogram, and anorectal manometric study were performed in 8 subjects with PD. Basal studies showing abnormalities were repeated following apomorphine administration. Prior defecographic abnormalities were normalized following apomorphine injection in 1 of 3 subjects and significant improvements in manometric parameters were observed in all 5 subjects who underwent repeat anorectal manometry. We conclude that apomorphine can correct anorectal dysfunction in PD, and that these abnormalities may be a consequence of dopamine deficiency secondary to the PD process. These findings may also have therapeutic implications.

Although more extensive research is required to fully characterize the pathophysiology of the gastrointestinal symptoms in PD, much of the presently available data suggest that the primary PD process is the major factor in the etiology of gut dysfunction in this patient population. This may be mediated by both central and peripheral mechanisms. Involvement of the dorsal motor nucleus of the vagus might produce dysfunction of muscles controlling deglutition and esophageal motility, thereby leading to drooling, dysphagia, and gastroesophageal reflux. The presence of Lewy bodies, the primary neuropathologic finding in the CNS in PD, in the myenteric plexus of both the esophagus and colon suggests that the PD process may also affect the enteric nervous system and contribute to the development of esophageal dysmotility and constipation through this peripheral mechanism. Dopamine receptors have been identified in the lower esophageal sphincter and the esophageal body of animals. If similarly present in humans, involvement of this dopaminergic system could contribute to the development of dysphagia and nausea of PD. Constipation may reflect both peripheral involvement, indicated by Lewy bodies in the colonic myenteric plexus, leading to colonic inertia, and central mechanisms, leading to pelvic floor dysfunction.

We have investigated the prevalence of gastrointestinal (GI) symptoms in 98 individuals with Parkinson's disease (PD) and in a control group of 50. Seventy-nine of those with PD were being treated with dopaminergic medications and 19 were untreated. Those symptoms occurring more frequently in PD patients than in controls included abnormal salivation, dysphagia, nausea, constipation, and defecatory dysfunction. Except for defecatory dysfunction, symptoms did not correlate with treatment but instead correlated with disease severity. This suggests that the GI symptoms of PD reflect direct involvement in the GI tract by the primary disease process.

It has been recently suggested that increased muscle protein degradation during injury or infection is at least partially mediated by the increased production of prostaglandin E2 in muscle, and some have suggested that cyclooxygenase inhibitors might decrease protein loss in injured or septic patients. In these experiments, fractional synthesis rates of mixed muscle and liver protein and whole-body tyrosine flux were measured by constant intravenous infusion of tyrosine labeled with carbon 14 in 17 rats with sham operations and 15 severely septic rats with or without indomethacin treatment (20 mg/kg/d). Fractional synthesis rates in muscle and liver were decreased in late sepsis and were lowest in the septic group receiving indomethacin. Unlike the fractional synthesis rate, which was affected by indomethacin in septic rats only, tyrosine flux was significantly lower in indomethacin-treated rats with sham operations and those with sepsis. Although indomethacin reduced total-body protein breakdown during sepsis, it was also associated with lower plasma albumin levels and with decreased protein synthesis in muscle and liver at a time when the survival of the septic host may be dependent on its ability to produce new protein for a variety of vital functions. These results do not support the use of indomethacin in sepsis.

Acute renal failure in the surgical patient is accompanied by a state of hypermetabolism and increased catabolism. Nutritional therapy is therefore directed at the preservation of body cell mass and protein synthesis for repair of wounds and damaged renal tubuli and for maintenance of host defense mechanisms. We examined the effect of two levels of protein intake (18.4 +/- 1.4 and 30.8 +/- 2.4 mg N/100 g BW/day) and three different amino acid formulations (Freamine III, Nephramine, and a made-up mixture of Nephramine + Freamine HBC) on renal function following mercury chloride-induced acute renal failure in the rat. All animals suffered severe renal failure manifested by increased plasma urea and creatinine levels, decreased creatinine clearance, and increased fractional excretion of sodium. On day 4 of acute renal failure, rats receiving low dose amino acids had better-preserved renal function than those receiving high dose amino acids. However, the type of solution infused did not affect recovery of renal function.

The yeasts Candida utilis and Saccharomycopsis fibuliger were propagated as a source of single-cell protein in a continuous, mixed, aerobic, single-stage cultivation on blancher water generated during potato processing. A series of steady-state experiments based on a two-level factorial design, half-replicate modified with an intermediate experiment, was performed to determine the effect of pH, 3.8 to 4.8; dissolved oxygen, 42 to 80% saturation; dilution rate, 0.17 to 0.31 h(-1); and temperature, 27 to 32 degrees C on the amount of carbon consumed, the rate of carbon consumption (R(c)), the amount of reducing sugar consumed, the rate of sugar consumption (R(g)), the amount of protein produced, the rate of protein production (R(p)), the yield from carbon, and the yield from reducing sugar. The results were analyzed by stepwise multiple regression and Fisher's least significant difference test. Analyses showed that high dilution rates resulted in increased R(c), R(g), and R(p) and indicated that a rate of 0.31 h(-1) was below the critical dilution rate. A temperature of 32 degrees C increased the amount of carbon consumed by 34%. A pH of 4.3 to 4.8 increased the amount of protein produced. The yield from carbon was constant, and the relatively high yield from reducing sugar indicated that other substrates were consumed. Dissolved oxygen was in excess at 42% saturation and above. Since C. utilis predominated the mixed cultures and amylase production appeared to be limited, a single-stage fermentation lacked efficiency. The experimental design allowed preliminary optimization of major environmental variables with relatively few experiments and provided a basis for future kinetic studies.

The behavioral and neurochemical effects of four intraventricular infusions of octopamine (3,200 micrograms), tryptophan (800 micrograms), and octopamine plus tryptophan delivered over 6 hours was studied in rats after performing a portacaval anastomosis or a sham operation. After each infusion, each animal was rated for neurologic depression with a 17 point test battery. Although overt coma was not induced, octopamine infusions severely depressed neurologic function. Concentrations of norepinephrine, dopamine, and serotonin in the brain were significantly decreased after the infusion of octopamine. Levels of norepinephrine in the brain were significantly correlated with neurologic status and greater depletion of norepinephrine was associated with greater neurologic depression. These studies demonstrate that infusing large amounts of the trace amine octopamine depresses behavior in the rat and this depression is most closely associated with depletion of stores of norepinephrine in the brain.

Evidence from several sources suggest that blood-brain transport of the large neutral amino acids (NAA) is abnormal in animals with a portacaval anastomosis (PCA) and in patients with liver cirrhosis and portal-systemic shunting and encephalopathy, but the underlying mechanisms are unknown. After PCA, the concentration of glutamine (Gln) in brain is markedly increased as a by-product of cerebral ammonia detoxification, and the rate of efflux of Gln from brain is also increased. The following studies were undertaken to clarify the relationships among plasma and brain concentrations of NAA after PCA in rats and to examine the relationship of brain Gln concentration to plasma and brain NAA concentrations. After PCA plasma phenylalanine, tyrosine and histidine were elevated and leucine, isoleucine and valine were lowered. In brain, phenylalanine, tyrosine, histidine and methionine were markedly elevated after PCA and their concentrations in brain far exceeded the concentrations in plasma. Analyses of single, partial and multiple correlations of plasma NAA ratios expressed as plasma competitor function (PCF), brain NAA and brain Gln showed significant correlations between PCF nd brain NAA in shunted rats. A better correlation was found between brain NAA and brain Gln. Correlation coefficients obtained from multiple correlation analysis equalled or exceeded those obtained in the partial correlation or in the single correlation, suggesting that the effects of PCF and brain Gln on brain NAA were separate and additive. Gln was shown to compete with other NAA for blood brain transport by inhibiting brain 14C phenylalanine uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

The goal of nutritional support in sepsis is, as in other conditions, to prevent the use of endogenous protein as an energy substrate and, ideally, to promote the synthesis of proteins specifically required in responding to the particular insult or stress at hand. This entails provision of an utilizable fuel, in sufficient quantity, that does not inhibit the use of endogenous nonprotein sources; preservation of the existing protein mass by minimizing skeletal muscle and visceral proteolysis; provision of amino acids in sufficient quantity and in the appropriate proportions such that protein synthesis is optimized. Specifically, this includes the synthesis of those proteins required to maintain hyperdynamic function of the essential organs as well as the hepatic and leukocytic synthesis of proteins required in immunologic defense. This study has assessed one aspect of this goal during the administration of nutrient solutions differing primarily in branched chain amino acid content. We conclude that leucine is fundamental among the branched chain amino acids for reducing skeletal muscle proteolysis. Solutions designed for sepsis or stress should, therefore, contain adequate amounts of this amino acid.

The efficacy and side effects of two elemental diets were studied. Twenty young Sprague-Dawley rats were fed one of three different diets. Group I (n = 7) was fed Vivonex-HN (VIV) ad lib; group II (n = 7) was given Criticare-HN (CRI), pair-fed to group I (the two elemental diets were given in glass bottles); group III was fed regular rat chow and served as control (CON). Body weight (WT), food intake, and nitrogen balance (NB) were measured daily. After 21 days, change in body weight was similar in the three groups (VIV = 64.9 +/- 3.2%; CRI = 59.6 +/- 3.3%; CON = 63.9 +/- 4.8%). Cumulative nitrogen balance was also similar in the two groups fed elemental diets (VIV = 4788 +/- 277 mg N; CRI = 4690 +/- 118 mg N), but in both these groups it was less than the control group fed chow (8060 +/- 85 mg N). Blood urea nitrogen (BUN) on the last day was higher in the VIV group (12.9 +/- 1.22 mg/dl) than in the CRI group (9.43 +/- 0.43 mg/dl), but in both study groups it was lower than in the CON group (17.2 +/- 1.08 mg/dl), although nitrogen intake was higher in the control (ad lib) group. SGPT was similar in the two elemental diets but higher than in CON. Liver weights were higher in the CRI group, probably abnormally so and likely due to increased fat content. Both diets had similar efficacy in nutritional support.

During infusion into rats with a portacaval shunt of either ammonium (NH4+) salts alone or NH4+ salts combined with the three branched-chain amino acids (BCAAs) in equimolar quantities, we assessed neurologic function and measured plasma and brain ammonia and amino acid levels and the brain content of amine neurotransmitters and their metabolites. Survival was lengthened and neurologic function was preserved longer in rats receiving BCAAs. Infusion of BCAAs resulted in lower plasma and brain ammonia concentrations compared with rats receiving NH4+ salts alone. Plasma glutamine and alanine levels were higher in rats receiving BCAAs, suggesting increased ammonia detoxification. Loss of neurologic function, regardless of which solution was infused, eventually occurred and corresponded with decreased brain norepinephrine and increased brain alanine levels. These results suggest that BCAAs can protect against hyperammonemia by stimulating the peripheral detoxification of ammonia.

To examine alterations in amino acid metabolism after trauma and sepsis, male Sprague-Dawley rats underwent no operation (control, CON), celiotomy (trauma, TRA), or cecal ligation and puncture (sepsis, CLP). After 16 hr, plasma amino acid concentrations were determined. A second group of similarly prepared animals underwent isolated liver perfusion, and net amino acid uptake or release was determined over 30 min. Sepsis significantly decreased total amino acid concentration in portal plasma (CON, 3486 +/- 156 nmole/ml; TRA, 3407 +/- 150 nmole/ml; CLP, 2738 +/- 148 nmole/ml). Glutamine concentrations were uniformly lower in portal plasma than in arterial plasma in all states. There were depressed concentrations of the branched chain amino acids (BCAA) in portal plasma after trauma but not sepsis. In the isolated liver perfusion model, a marked increase in amino acid uptake was induced by sepsis (CON, 39.9 +/- 7.9 mumol/g liver protein; TRA, 49.5 +/- 17.3 mumol/g liver protein; CLP, 124 +/- 11 mumol/g liver protein). In addition, there was significantly greater uptake of threonine, asparagine, proline, methionine, tyrosine, and arginine. Although the BCAA isoleucine and valine were taken up to a greater extent in sepsis, the overall BCAA uptake was not significantly greater in sepsis than in control (CON 6.92 +/- 2.15 mumol/g liver protein vs CLP 15.8 +/- 1.9 mumol/g liver protein). The greatest increase in uptake following sepsis was among the gluconeogenic precursor amino acids alanine, glycine, threonine, and serine (CON, 27.0 +/- 4.2 mumol/g liver protein, TRA, 38.8 +/- 8.9 mumol/g liver protein; CLP, 62.8 +/- 6.0 mumol/g liver protein).(ABSTRACT TRUNCATED AT 250 WORDS)