Platelets after burn injury - hemostasis and beyond.

Burn injuries are common and often life-threatening trauma. With this trauma comes an interruption of normal hemostasis, with distinct impacts on platelets. Our interest in the relationships between burn injury and platelet function stems from two key perspectives: platelet function is a vital component of acute responses to injury, and furthermore the incidence of cardiovascular disease (CVD) is higher in burn survivors compared to the general population. This review explores the impact of burn injury on coagulation, platelet function, and the participation of platelets in immunopathology. Potential avenues of further research are explored, and consideration is given to what therapies may be appropriate for mediating post-burn thrombopathology.

Clofazimine for Treatment of Cryptosporidiosis in Human Immunodeficiency Virus Infected Adults: An Experimental Medicine, Randomized, Double-blind, Placebo-controlled Phase 2a Trial.

BACKGROUND: We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis. METHODS: We performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis. RESULTS: Twenty part A and 10 part B participants completed the study ATP. Almost all part A participants had high viral loads and low CD4 counts, consistent with failure of antiretroviral (ARV) therapy. At study entry, the part A CFZ group had higher Cryptosporidium shedding, total stool weight, and more diarrheal episodes compared with the placebo group. Over the inpatient period, compared with those who received placebo, the CFZ group Cryptosporidium shedding increased by 2.17 log2 Cryptosporidium per gram stool (95% upper confidence limit, 3.82), total stool weight decreased by 45.3 g (P = .37), and number of diarrheal episodes increased by 2.32 (P = .87). The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. One placebo and 3 CFZ participants died during the study. Plasma levels of CFZ in participants with cryptosporidiosis were 2-fold lower than in part B controls. CONCLUSIONS: Our findings do not support the efficacy of CFZ for the treatment of cryptosporidiosis in a severely immunocompromised HIV population. However, this trial demonstrates a pathway to assess the therapeutic potential of drugs for cryptosporidiosis treatment. Screening persons living with HIV for diarrhea, and especially Cryptosporidium infection, may identify those failing ARV therapy. CLINICAL TRIALS REGISTRATION: NCT03341767.

Laboratory and clinical impacts of an overnight laboratory service.

Delayed initiation of effective antimicrobial therapy for sepsis is associated with increased mortality. Whilst automated blood culture machines operate continuously, this does not align with conventional staff working hours and so turn-around-times (TAT) for reporting gram stains to clinicians are 3-7 times longer for blood cultures that flag positive overnight. We retrospectively compared laboratory TATs and clinical outcomes for blood cultures from 183 patients that flagged positive overnight during a 4-month period before and after the implementation of an overnight laboratory service. Enterobacterales and urinary tract infections were the most frequent pathogens and clinical syndrome respectively, and the prevalence of multi-resistant organisms was 15%. Compared with the pre-implementation period, the post-implementation period was associated with shorter median time from blood culture positivity to gram stain (7.4 vs 1.2 h), first genus level identification (7.2 vs 5.8 h) and first antimicrobial susceptibility result (24.1 vs 7.9 h). Similarly, the median time from blood culture positivity to clinicians first being informed was significantly shorter (9.2 vs 1.3 h). After removal of likely contaminants, 78% of patients were on effective empiric antimicrobials and for patients on ineffective empiric antimicrobials, effective therapy was initiated a median of 3.2 h sooner during the post-implementation period, without impact on mortality. Implementation of an overnight laboratory service was associated with significantly faster TAT for reporting blood culture results and more prompt initiation of effective antimicrobials for patients receiving ineffective empiric therapy, improving attainment of sepsis management goals.

Extreme angle, tip-tilt MEMS micromirror enabling full hemispheric, quasi-static optical coverage.

Beam steering is essential for a variety of optical applications such as communication, LIDAR, and imaging. Microelectromechanical system (MEMS) mirrors are an effective method of achieving modest speeds and angular range at low cost. Typically there are a number of tradeoffs considered when designing a tip-tilt mirror, such as tilt angle and speed. For example, many mirrors are designed to scan at their resonant frequency to achieve large angles. This is effective for a scanning mode; however, this makes the device slow and ineffective as a galvo (quasi-static). Here, we present a magnetic MEMS mirror with extreme quasi-static mechanical tilt angles of ±60° (±120° optical) about two rotation axes. This micromirror enables full hemispheric optical coverage without compromising speed; settling in 4.5 ms using advanced drive techniques. This mirror will enable new applications for MEMS micromirrors previously thought impossible due to their limited angular range and speed.

Effect of an Otic Milbemycin Oxime Formulation on Tegastes acroporanus Infesting Corals.

The copepod Tegastes acroporanus is a notorious pest of captive corals in the genus Acropora. In recent years, infestations of T. acroporanus have become widespread among public aquaria and coral propagation facilities and have been largely controlled with the extra-label use of milbemycin oxime formulations (Carl 2008). Many of these drug formulations (which were intended for dogs) have been discontinued by their manufacturers in favor of multidrug products, many of which are unsuitable for corals, forcing experimentation with alternatives. This report provides the first data on populations of T. acroporanus treated with milbemycin oxime and documents the first known use of an otic solution, MilbeMite Otic (Novartis Animal Health U.S., Greensboro, North Carolina), against copepods on live corals. MilbeMite Otic was found to be soluble in seawater and successful at eradicating T. acroporanus in a large exhibit over the course of 6-h waterborne baths (n = 12) at 0.167 µg/L. The resident population of T. acroporanus was also quantified before each treatment to provide the first estimates of coral parasite burden in response to the application of a waterborne chemotherapeutic agent. Received November 19, 2015; accepted June 7, 2016 Published online October 24, 2016.

Hepatic compartmentalization of exhausted and regulatory cells in HIV/HCV-coinfected patients.

Accelerated intrahepatic hepatitis C virus (HCV) pathogenesis is likely the result of dysregulation within both the innate and adaptive immune compartments, but the exact contribution of peripheral blood and liver lymphocyte subsets remains unclear. Prolonged activation and expansion of immunoregulatory cells have been thought to play a role. We determined immune cell subset frequency in contemporaneous liver and peripheral blood samples from chronic HCV-infected and HIV/HCV-coinfected individuals. Peripheral blood mononuclear cells (PBMC) and biopsy-derived liver-infiltrating lymphocytes from 26 HIV/HCV-coinfected, 10 chronic HCV-infected and 10 HIV-infected individuals were assessed for various subsets of T and B lymphocytes, dendritic cell, natural killer (NK) cell and NK T-cell frequency by flow cytometry. CD8(+) T cells expressing the exhaustion marker PD-1 were increased in HCV-infected individuals compared with uninfected individuals (P = 0.02), and HIV coinfection enhanced this effect (P = 0.005). In the liver, regulatory CD4(+) CD25(+) Foxp3(+) T cells, as well as CD4(+) CD25(+) PD1(+) T cells, were more frequent in HIV/HCV-coinfected than in HCV-monoinfected samples (P < 0.001). HCV was associated with increased regulatory T cells, PD-1(+) T cells and decreased memory B cells, regardless of HIV infection (P ≤ 0.005 for all). Low CD8(+) expression was observed only in PD-1(+) CD8(+) T cells from HCV-infected individuals and healthy controls (P = 0.002) and was associated with enhanced expansion of exhausted CD8(+) T cells when exposed in vitro to PHA or CMV peptides. In conclusion, in HIV/HCV coinfection, ongoing HCV replication is associated with increased regulatory and exhausted T cells in the periphery and liver that may impact control of HCV. Simultaneous characterization of liver and peripheral blood highlights the disproportionate intrahepatic compartmentalization of immunoregulatory T cells, which may contribute to establishment of chronicity and hepatic fibrogenesis in HIV coinfection.

Component reductions in oxygen delivery generate variable haemodynamic and stress hormone responses.

BACKGROUND: In clinical practice, global oxygen delivery (DO2) is often considered as a whole; however pathological and adaptive responses after a decrease in individual constituents of the DO2 equation (cardiac output, haemoglobin, oxyhaemoglobin saturation) are likely to be diverse. We hypothesized that an equivalent decrease in DO2 after reductions in each separate component of the equation would result in different haemodynamic, tissue oxygenation, and stress hormonal responses. METHODS: Anaesthetized, fluid-resuscitated male Wistar rats were subjected to circulatory, anaemic, or hypoxic hypoxia (by haemorrhage, isovolaemic haemodilution, and breathing a hypoxic gas mix, respectively), produced either rapidly over 5 min or graded over 30 min, to a targeted 50% decrease in global oxygen delivery. Sham-operated animals acted as controls. Measurements were made of haemodynamics, skeletal muscle tissue oxygen tension, blood gas analysis, and circulating stress hormone levels. RESULTS: Whereas haemorrhage generated the largest decrease in cardiac output, and the greatest stress hormone response, haemodilution had the most marked effect on arterial pressure. In contrast, rapid hypoxaemia produced a minor impact on global haemodynamics yet induced the greatest decrease in regional oxygenation. A greater degree of hyperlactataemia was observed with graded insults compared with those administered rapidly. CONCLUSIONS: Decreasing global oxygen delivery, achieved by targeted reductions in its separate components, induces varying circulatory, tissue oxygen tension, and stress hormone responses. We conclude that not all oxygen delivery is the same; this disparity should be emphasized in classical teaching and re-evaluated in patient management.

The accumulation of exercise and postprandial endothelial function in boys.

The purpose of this study was to investigate the effect of accumulating 60 min of exercise on endothelial function and triacylglycerol concentrations following the ingestion of a high-fat breakfast and lunch in 14 adolescent boys (aged 12 to 14 years). Two, 2-day main trials (control and exercise) were completed in a counter-balanced, cross-over design. Participants were inactive on day 1 of the control trial but on day 1 of the exercise trial completed 6 × 10 min runs at 70% of peak oxygen uptake, spread over the day. On day 2, triacylglycerol concentrations and flow-mediated dilation (FMD) were measured prior to, and following, ingestion of the high-fat meals. In the control trial, FMD was reduced by 30% and 33% (P < 0.001) following the high-fat breakfast and lunch; following exercise these reductions were negated (main effect trial, P = 0.002, interaction effect trial × time, P < 0.001). The total and incremental areas under the triacylglycerol concentration vs time curve were reduced by 11% and 16% in the exercise trial; however, these differences were not significant (P > 0.05). These results support the concept of accumulating physical activity for health in adolescents as the accumulated exercise attenuated the decline in FMD seen following the consumption of high-fat meals.

Multifaceted roles of CCAR family proteins in the DNA damage response and cancer.

The cell cycle apoptosis regulator (CCAR) family of proteins consists of two proteins, CCAR1 and CCAR2, that play a variety of roles in cellular physiology and pathology. These multidomain proteins are able to perform multiple interactions and functions, playing roles in processes such as stress responses, metabolism, and the DNA damage response. The evolutionary conservation of CCAR family proteins allows their study in model organisms such as Caenorhabditis elegans, where a role for CCAR in aging was revealed. This review particularly highlights the multifaceted roles of CCAR family proteins and their implications in the DNA damage response and in cancer biology.

Can the ABILHAND handle manual ability in MS?

BACKGROUND: Hand dysfunction is common in multiple sclerosis (MS). Recent interest has focused on incorporating patient-reported outcome (PRO) instruments into clinical trials. Nevertheless, examinations are rare in MS of existing manual ability measures. OBJECTIVES: The objective of this paper is to evaluate the 23-item ABILHAND, developed for use after stroke, in people with MS, comparing the findings from two psychometric approaches. METHODS: We analysed ABILHAND data from 300 people with MS using: 1) traditional psychometric methods (data completeness, scaling assumptions, reliability, internal and external construct validity); and 2) Rasch measurement methods (including targeting, item response category ordering, data fit to the Rasch model, spread of item locations, item scoring bias, item stability, reliability, person response validity). RESULTS: Traditional psychometric methods implied ABILHAND was reliable and valid in this sample. Rasch measurement methods supported this finding. The three-category scoring function worked as intended and item fit to Rasch model expectations was acceptable. The 23 items (location range -3.16 to +2.73 logits) mapped a continuum of manual ability. Reliability was high (Person Separation Index (PSI) = 0.95). CONCLUSION: Both psychometric evaluations supported ABILHAND as a robust manual ability PRO measure for MS. Rasch measurement methods were more informative and, consistent with its role of detecting anomalies, identified ways of advancing further ABILHAND's measurement performance to reduce any potential for type II errors in clinical trials.

Baseline CD4+ T-cell counts predict HBV viral kinetics to adefovir treatment in lamivudine-resistant HBV-infected patients with or without HIV infection.

BACKGROUND: Coinfection with HIV and hepatitis B virus (HBV) substantially alters the course of HBV. Directly acting anti-HBV agents suppress HBV viral levels; however, the kinetics of HBV decline in mono- and coinfected persons have not been evaluated. We investigated the role of baseline CD4+ T-cell counts as a predictor of HBV response to adefovir (ADV) therapy in chronic HBV with and without HIV coinfection. METHODS: We conducted a double-blind, randomized, placebo-controlled study of HIV-infected (n = 12) and uninfected (n = 5) chronic HBV patients treated with ADV. Five HIV uninfected patients received ADV; the HIV+ patients received ADV or placebo for a total of 48 weeks. At the end of 48 weeks, all patients received open-label ADV for an additional 48 weeks. HBV, HIV viral loads, CD4+ T-cell counts, and safety labs were performed on days 0, 1, 3, 5, 7, 10, 14, and 28 and then every 4 weeks. RESULTS: Lower HBV slopes were observed among coinfected compared to monoinfected patients (P = .027 at 4 weeks, P = .019 at 24 weeks, and P = .045 at 48 weeks). Using a mixed model analysis, we found a significant difference between the slopes of the 2 groups at 48 weeks (P = .045). Baseline CD4+ T-cell count was the only independent predictor of HBV decline in all patients. CONCLUSION: HIV coinfection is associated with slower HBV response to ADV. Baseline CD4+ T-cell count and not IL28B genotype is an independent predictor of HBV decline in all patients, emphasizing the role of immune status on clearance of HBV.

Infanticide and reproductive restraint in a polygynous social mammal.

Alpha male chacma baboons experience uncontested access to individual estrus females. Consequently, alpha male paternity certainty is high and underpins significant levels of infanticide by immigrant males that, in turn, has selected for male defense of infants. There is also, however, a high probability that alpha males will be absent during the period when their own offspring are vulnerable, suggesting selection for additional countermeasures. We use data from a long-term study to test the prediction that alpha male chacma baboons cede reproductive opportunities to subordinate males and that this leads to the presence of other fathers that can serve as a buffer against infanticidal attack. We found that subordinate males obtained significantly more conceptive opportunities than predicted by priority of access alone, and that this occurred because alpha males did not consort all receptive periods. There was no evidence that this was due to energetic constraint, large male cohorts, alpha male inexperience, or the competitive strength of queuing subordinates. The number of males who benefited from concession and the length of time that they were resident relative to those who did not benefit in this way greatly reduced the probability that infants of alpha males would face immigrant males without a surrogate father whose own offspring were vulnerable. The absence of such males was associated with observed infanticide as well as, unexpectedly, an increased likelihood of takeover when alpha males with vulnerable infants were present.

The socio-economic challenges of managing pathogen evolution in agriculture.

Genetic resistance forms the foundation of infectious disease management in crops. However, rapid pathogen evolution is causing the breakdown of resistance and threatening disease control. Recent research efforts have identified strategies for resistance gene deployment that aim to disrupt pathogen adaptation and prevent breakdown. To date, there has been limited practical uptake of such strategies. In this paper, we focus on the socio-economic challenges associated with translating applied evolutionary research into scientifically informed management strategies to control pathogen adaptation. We develop a conceptual framework for the economic valuation of resistance and demonstrate that in addition to various direct benefits, resistance delivers considerable indirect and non-market value to farmers and society. Incentives for stakeholders to engage in stewardship strategies are complicated by the uncertain timeframes associated with evolutionary processes, difficulties in assigning ownership rights to genetic resources and lack of governance. These interacting biological, socio-economic and institutional complexities suggest that resistance breakdown should be viewed as a wicked problem, with often conflicting imperatives among stakeholders and no simple cause or solution. Promoting the uptake of scientific research outcomes that address complex issues in sustainable crop disease management will require a mix of education, incentives, legislation and social change. This article is part of the theme issue 'Infectious disease ecology and evolution in a changing world'.

Variation in infectivity and aggressiveness in space and time in wild host-pathogen systems: causes and consequences.

Variation in host resistance and in the ability of pathogens to infect and grow (i.e. pathogenicity) is important as it provides the raw material for antagonistic (co)evolution and therefore underlies risks of disease spread, disease evolution and host shifts. Moreover, the distribution of this variation in space and time may inform us about the mode of coevolutionary selection (arms race vs. fluctuating selection dynamics) and the relative roles of G × G interactions, gene flow, selection and genetic drift in shaping coevolutionary processes. Although variation in host resistance has recently been reviewed, little is known about overall patterns in the frequency and scale of variation in pathogenicity, particularly in natural systems. Using 48 studies from 30 distinct host-pathogen systems, this review demonstrates that variation in pathogenicity is ubiquitous across multiple spatial and temporal scales. Quantitative analysis of a subset of extensively studied plant-pathogen systems shows that the magnitude of within-population variation in pathogenicity is large relative to among-population variation and that the distribution of pathogenicity partly mirrors the distribution of host resistance. At least part of the variation in pathogenicity found at a given spatial scale is adaptive, as evidenced by studies that have examined local adaptation at scales ranging from single hosts through metapopulations to entire continents and - to a lesser extent - by comparisons of pathogenicity with neutral genetic variation. Together, these results support coevolutionary selection through fluctuating selection dynamics. We end by outlining several promising directions for future research.

Stronger hepatitis C virus-specific CD8+ T-cell responses in HIV coinfection.

Hepatitis C virus (HCV) is a widespread chronic infection that shares routes of transmission with human immunodeficiency virus (HIV). Thus, coinfection with these viruses is a relatively common and growing problem. In general, liver disease develops over years with HIV coinfection, when compared to decades in HCV monoinfection. The role of the immune system in the accelerated pathogenesis of liver disease in HIV/HCV coinfection is not clear. In this study, we compared the frequency, magnitude, breadth and specificity of peripheral blood CD4+ and CD8+ T-cell responses between HCV-monoinfected and HCV/HIV-coinfected individuals and between HIV/HCV-coinfected subgroups distinguished by anti-HCV antibody and HCV RNA status. While HIV coinfection tended to reduce the frequency and breadth of anti-HCV CD8+ T-cell responses in general, responses that were present were substantially stronger than in monoinfection. In all groups, HCV-specific CD4+ T-cell responses were rare and weak, independent of either nadir or concurrent CD4+ T-cell counts of HIV-infected individuals. Subgroup analysis demonstrated restricted breadth of CD8+ HCV-specific T-cell responses and lower B-cell counts in HIV/HCV-coinfected individuals without anti-HCV antibodies. The greatest difference between HIV/HCV-coinfected and HCV-monoinfected groups was substantially stronger HCV-specific CD8+ T-cell responses in the HIV-coinfected group, which may relate to accelerated liver disease in this setting.

Beyond the reach of traditional analyses: using Rasch to evaluate the DASH in people with multiple sclerosis.

BACKGROUND: Few upper limb functioning patient rating scales have been used in multiple sclerosis (MS) research and none developed specifically for people with MS. OBJECTIVES: In this study, we examined the Disabilities of the Arm, Shoulder and Hand (DASH) to determine its utility as a useful, scientifically robust and clinically meaningful tool in MS. METHODS: DASH data from 300 people with MS underwent two independent phases of psychometric analyses: (1) a traditional psychometric analysis (including data quality, scaling assumptions, reliability and validity); and (2) a Rasch analysis (including response option thresholds ordering, tests of fit, spread of item locations, residual correlations, and person separation index). RESULTS: Overall, the traditional psychometric analysis supported the DASH as a reliable and valid measure of upper limb function in people with MS. However, several issues were raised by the Rasch analysis that questioned the validity of the DASH, including misfit in 13/30 items, disordered item response option thresholds for 9/30 items, and six pairs of items with high residual correlations (> 0.60). CONCLUSION: Rasch analysis highlights areas for potential improvement for the use of the DASH. Our findings further support our previous arguments that traditional psychometric methods provide weak scale evaluations and can mislead clinicians as to the reliability and validity of outcome measures.

Providing an Evidence Base for Tissue Sampling and Culture Interpretation in Suspected Fracture-Related Infection.

BACKGROUND: The recent consensus definition for the diagnosis of fracture-related infection (FRI) includes the identification of indistinguishable microorganisms in at least 2 surgical deep-tissue specimens as a confirmatory criterion. However, this cut-off, and the total number of specimens from a patient with suspected FRI that should be sent for microbiological testing, have not been validated. We endeavored to estimate the accuracy of different numbers of specimens and diagnostic cut-offs for microbiological testing of deep-tissue specimens in patients undergoing surgical treatment for possible FRI. METHODS: A total of 513 surgical procedures in 385 patients with suspected FRI were included. A minimum of 2 surgical deep-tissue specimens were submitted for microbiological testing; 5 or more specimens were analyzed in 345 procedures (67%). FRI was defined by the presence of any confirmatory criteria other than microbiology. Resampling was utilized to model the sensitivity and specificity of diagnostic cut-offs for the number of surgical specimens yielding indistinguishable microorganisms and for the total number of specimens. The likelihood of detecting all clinically relevant microorganisms was also assessed. RESULTS: A diagnostic cut-off of at least 2 of 5 specimens with indistinguishable microorganisms identified by culture was 68% sensitive (95% confidence interval [CI], 62% to 74%) and 87% specific (95% CI, 81% to 94%) for the diagnosis of FRI. Two out of 3 specimens were 60% sensitive (95% CI, 55% to 66%) and 92% specific (95% CI, 88% to 96%). Submitting only 3 deep-tissue specimens risked missing clinically relevant microorganisms in at least 1 in 10 cases. CONCLUSIONS: The present study was the first to validate microbiological criteria for the diagnosis of FRI, supporting the current confirmatory diagnostic criteria for FRI. Analysis of at least 5 deep-tissue specimens in patients with possible FRI is recommended. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Enhanced conformational space sampling improves the prediction of chemical shifts in proteins.

A biased-potential molecular dynamics simulation method, accelerated molecular dynamics (AMD), was combined with the chemical shift prediction algorithm SHIFTX to calculate (1)H(N), (15)N, (13)Calpha, (13)Cbeta, and (13)C' chemical shifts of the ankyrin repeat protein IkappaBalpha (residues 67-206), the primary inhibitor of nuclear factor kappa-B (NF-kappaB). Free-energy-weighted molecular ensembles were generated over a range of acceleration levels, affording systematic enhancement of the conformational space sampling of the protein. We have found that the predicted chemical shifts, particularly for the (15)N, (13)Calpha, and (13)Cbeta nuclei, improve substantially with enhanced conformational space sampling up to an optimal acceleration level. Significant improvement in the predicted chemical shift data coincides with those regions of the protein that exhibit backbone dynamics on longer time scales. Interestingly, the optimal acceleration level for reproduction of the chemical shift data has previously been shown to best reproduce the experimental residual dipolar coupling (RDC) data for this system, as both chemical shift data and RDCs report on an ensemble and time average in the millisecond range.

FL-160 proteins of Trypanosoma cruzi are expressed from a multigene family and contain two distinct epitopes that mimic nervous tissues.

The partial sequence of a gene encoding the COOH terminus of a protein of apparent molecular weight of 160 kD associated with the flagellum of trypomastigotes of Trypanosoma cruzi (FL-160 now renamed to FL-160-1) has been previously reported. The COOH terminus of FL-160-1 has an epitope, defined by 12 amino acids, which molecularly miMics a nervous tissue antigen of 48 kD found in myenteric plexus, sciatic nerve, and a subset of cells in the central nervous system. We now report that FL-160 is a family of highly related genes. The sequence has been determined for the entire open reading frame (ORF) of one of the members of the FL-160 gene family (FL-160-2) and three other partial ORFs. Sequence analysis reveals the various members of the FL-160 gene family to be approximately 80% homologous in the predicted amino acid sequence, but all retain the 12-amino acid molecular mimicry epitope on the COOH terminus. Comparison of the sequence of FL-160-2 to other sequences demonstrates amino acid homology to bacterial sialidase (27%), members of the SA85 gene family (25-30%) and the shed acute-phase antigen/neuraminidase/trans-sialidase gene family (25-30%). Quantitative hybridization at high stringency suggests 750 copies of FL-160 are present in the DNA of each parasite. Reverse transcription and sequence analysis demonstrates that at least five of the members of the FL-160 gene family are transcribed. The NH2 terminus of one of the FL-160 gene products was expressed and antibodies prepared. Antibodies directed to either the COOH or the NH2 terminus of FL-160 bind a 160-kD T. cruzi protein. Both antibodies bind the surface membrane in the flagellar pocket of the trypomastigote. Antibodies to the NH2 terminus bind epineurium and scattered linear densities in sciatic nerve in a pattern distinct from the pattern with antibodies to the COOH terminus. Thus, there are at least two distinct molecular mimicry epitopes on the FL-160 molecule and both mimic epitopes found in nervous tissues. FL-160 may be involved in the generation of autoimmunity to nervous tissues by molecular mimicry, observed in chronic Chagas' disease.