The use of predator tags to explain reversal movement patterns in Atlantic salmon smolts (Salmo salar L.).

Acoustic telemetry has seen a rapid increase in utility and sophistication in recent years and is now used extensively to assess the behavior and survival rates of many aquatic animals, including the Atlantic salmon. As part of the salmon's complex life cycle, salmon smolts are thought to make a unidirectional migration from fresh water to the sea, which is initiated by changes in their physiology. However, some tag movement patterns do not conform with this and can be difficult to explain, particularly if the tagged fish has been eaten by a predator. This study combines the use of predator tags with machine learning techniques to understand the fate of migrating salmon smolts and thereby improve estimates for migration success. Over 3 years between 2020 and 2022, 217 salmon smolts (including wild and hatchery-reared ranched fish) were acoustically tagged and released into an embayment on the west coast of Ireland. Some tagged smolts were observed to return from the estuary back into a saline lagoon through which they had already migrated. To distinguish between the movement of a salmon smolt and that of a predator, predator tags were deployed in migrating smolts in 2021 and 2022. The addition of a temperature sensor in 2022 enabled the determination of predator type causing the returning movement. A significant number of predator tags were triggered, and the patterns of movement associated with these triggered tags were then used with two types of machine learning algorithms (hierarchical cluster analysis and random forest) to identify and validate the behavior of smolts tagged without extra sensors. Both models produced the same outputs, grouping smolts tagged with predator tags with smolts tagged without the additional sensors but showing similar movements. A mammalian predator was identified as the cause of most reversal movement, and hatchery-reared ranched smolts were found to be more likely predated upon by this predator than wild smolts within the lake and the estuary. However, overall migration success estimates were similar for both wild and hatchery-reared ranched fish. This study highlights the value of predator tags as an essential tool in the overall validation of detection data.

Systematic Review of Piperacillin-Tazobactam and Vancomycin Y-Site Compatibility: Consideration of Concentration and Solution Variability.

Simultaneous administration of vancomycin and piperacillin-tazobactam (VPT) poses significant challenges related to physical and chemical compatibility, as well as clinical practice. A systematic review of available literature related to VPT Y-site compatibility was performed. Data was collected from primary and tertiary sources. Seven articles were included in addition to one internal assessment and one review article and information from tertiary drug databases. The literature supports the simultaneous administration via Y-site of piperacillin-tazobactam 33.75 mg/mL in normal saline (NS) and vancomycin 4 to 8 mg/mL in NS. The same drug products at differing concentrations, diluents, storage conditions, or preparations outside of this recommendation should be considered incompatible.

Impact of a Multifaceted Intervention on Antibiotic Prescribing for Cystitis and Asymptomatic Bacteriuria in 23 Community Hospital Emergency Departments.

Background: Urinary tract infections (UTIs) are over-diagnosed and over-treated in the emergency department (ED) leading to unnecessary antibiotic exposure and avoidable side effects. However, data describing effective large-scale antimicrobial stewardship program (ASP) interventions to improve UTI and asymptomatic bacteriuria (ASB) management in the ED are lacking. Methods: We implemented a multifaceted intervention across 23 community hospital EDs in Utah and Idaho consisting of in-person education for ED prescribers, updated electronic order sets, and implementation/dissemination of UTI guidelines for our healthcare system. We compared ED UTI antibiotic prescribing in 2021 (post-intervention) to baseline data from 2017 (pre-intervention). The primary outcomes were the percent of cystitis patients prescribed fluoroquinolones or prolonged antibiotic durations (>7 days). Secondary outcomes included the percent of patients treated for UTI who met ASB criteria, and 14-day UTI-related readmissions. Results: There was a significant decrease in prolonged treatment duration for cystitis (29% vs 12%, P < .01) and treatment of cystitis with a fluoroquinolone (32% vs 7%, P < .01). The percent of patients treated for UTI who met ASB criteria did not change following the intervention (28% pre-intervention versus 29% post-intervention, P = .97). A subgroup analysis indicated that ASB prescriptions were highly variable by facility (range 11%-53%) and provider (range 0%-71%) and were driven by a few high prescribers. Conclusions: The intervention was associated with improved antibiotic selection and duration for cystitis, but future interventions to improve urine testing and provide individualized prescriber feedback are likely needed to improve ASB prescribing practice.

Towards an in situ non-lethal rapid test to accurately detect the presence of the nematode parasite, Anguillicoloides crassus, in European eel, Anguilla anguilla.

Anguillicoloides crassus is an invasive nematode parasite of the critically endangered European eel, Anguilla anguilla, and possibly one of the primary drivers of eel population collapse, impacting many features of eel physiology and life history. Early detection of the parasite is vital to limit the spread of A. crassus, to assess its potential impact on spawning biomass. However accurate diagnosis of infection could only be achieved via necropsy. To support eel fisheries management we developed a rapid, non-lethal, minimally invasive and in situ DNA-based method to infer the presence of the parasite in the swim bladder. Screening of 131 wild eels was undertaken between 2017 and 2019 in Ireland and UK to validate the procedure. DNA extractions and PCR were conducted using both a Qiagen Stool kit and in situ using Whatman qualitative filter paper No1 and a miniPCR DNA Discovery-System™. Primers were specifically designed to target the cytochrome oxidase mtDNA gene region and in situ extraction and amplification takes approximately 3 h for up to 16 individuals. Our in-situ diagnostic procedure demonstrated positive predictive values at 96% and negative predictive values at 87% by comparison to necropsy data. Our method could be a valuable tool in the hands of fisheries managers to enable infection control and help protect this iconic but critically endangered species.

Maternal and Child Health Pipeline Training Programs: A Description of Training Across 6 Funded Programs.

PURPOSE: The HRSA-funded maternal and child health pipeline training programs (MCHPTPs) are a response to the critical need to diversify the MCH workforce, as a strategy to reduce health disparities in MCH populations. These MCHPTPs support students from undergraduate to graduate education and ultimately into the MCH workforce. DESCRIPTION: The models and components of training across the six MCHPTPs funded in 2016-2021 are summarized, to examine the design and delivery of undergraduate pipeline training and the insights gained across programs. ASSESSMENT: Strategies that emerged across training programs were organized into three themes: recruitment, support for student persistence (in education), and pipeline-to-workforce intentionality. Support for student persistence included financial support, mentoring, creating opportunity for students to develop a sense of belonging, and the use of research as a tool to promote learning and competitiveness for graduate education. Finally, the link to Maternal and Child Health Bureau (MCHB) long-term training and other MCHB opportunities for professional development contributed significant nuance to the pipeline-to-workforce objectives of these programs. CONCLUSIONS: The MCHPTPs not only increase the diversity of the MCH workforce, they also actively prepare the next generation of MCH leaders. The intentional connection of undergraduates to the infrastructure and continuum of MCH training, underscores the comprehensive impact of this funding.

Antibiotic prescribing for adult bacteriuria and pyuria in community hospital emergency departments.

OBJECTIVE: To describe emergency department (ED) antibiotic prescribing for urinary tract infections (UTIs) and asymptomatic bacteriuria (ASB) and to identify improvement opportunities. METHODS: Patients treated for UTI in 16 community hospital EDs were reviewed to identify prescribing that was unnecessary (any treatment for ASB, duration >7 days for cystitis or >14 days for pyelonephritis) or suboptimal [ineffective antibiotics (nitrofurantoin/fosfomycin) or duration <7 days for pyelonephritis]. Duration criteria were based on recommendations for complicated UTI since criteria for uncomplicated UTI were not reviewed. 14-day repeat ED visits were evaluated. RESULTS: Of 250,788 ED visits, UTI was diagnosed in 13,466 patients (5%), and 1427 of these (11%) were manually reviewed. 286/1427 [20%, 95% CI: 18-22%] met criteria for ASB and received 2068 unnecessary antibiotic days [mean (±SD) 7 (2) days]. Mean treatment duration was 7 (2) days for cystitis and 9 (2) days for pyelonephritis. Of 446 patients with cystitis, 128 (29%) were prescribed >7 days (total 396 unnecessary). Of 422 pyelonephritis patients, 0 (0%) were prescribed >14 days, 20 (5%) were prescribed <7 days, and 9 (2%) were given ineffective antibiotics. Overall, prescribing was unnecessary or suboptimal in 443/1427 [31%, 95% CI: 29-33%] resulting in 2464/11,192 (22%) unnecessary antibiotic days and 8 (0.5%) preventable ED visits. CONCLUSIONS: Among reviewed patients, poor UTI prescribing in 16 EDs resulted in unnecessary antibiotic days and preventable readmissions. Key areas for improvement include non-treatment of ASB and shorter durations for cystitis.

Self-rated health of Middle Eastern immigrants in the US: a national study.

OBJECTIVES: The aim of the study was to examine self-rated health (SRH) of Middle Eastern immigrants in the US compared with US-born non-Hispanic whites and to examine factors associated with fair/poor SRH among Middle Eastern immigrants in the US. STUDY DESIGN: We used a cross-sectional design to analyze the National Health Interview Survey from 2001 to 2015. METHODS: Secondary survey analysis procedures were conducted using the SAS program, with a total of 3,966 Middle Eastern and 731,285 US-born non-Hispanic whites. Descriptive statistics and regression analyses were used. RESULTS: Middle Eastern immigrants had significantly higher rates of fair/poor SRH than US-born whites across the three survey waves. Reporting symptoms of serious psychological distress, older age (60+ years), current alcohol-drinking status, and having a family member with disability were the factors associated significantly with higher odds of reporting fair/poor SRH in Middle Eastern immigrants, whereas education was a protecting factor of fair/poor SRH. CONCLUSIONS: This study indicates that Middle Eastern immigrants are one of the US immigrant populations that report poor health status, which reveals the need for health policy attention to reduce health disparities.

Alpha galactosidase A activity in Parkinson's disease.

Glucocerebrosidase (GCase, deficient in Gaucher disease) enzymatic activity measured in dried blood spots of Parkinson's Disease (PD) cases is within healthy range but reduced compared to controls. It is not known whether activities of additional lysosomal enzymes are reduced in dried blood spots in PD. To test whether reduction in lysosomal enzymatic activity in PD is specific to GCase, we measured GCase, acid sphingomyelinase (deficient in Niemann-Pick disease types A and B), alpha galactosidase A (deficient in Fabry), acid alpha-glucosidase (deficient in Pompe) and galactosylceramidase (deficient in Krabbe) enzymatic activities in dried blood spots of PD patients (n = 648) and controls (n = 317) recruited from Columbia University. Full sequencing of glucocerebrosidase (GBA) and the LRRK2 G2019S mutation was performed. Enzymatic activities were compared between PD cases and controls using t-test and regression models adjusted for age, gender, and GBA and LRRK2 G2019S mutation status. Alpha galactosidase A activity was lower in PD cases compared to controls both when only non-carriers were included (excluding all GBA and LRRK2 G2019S carriers and PD cases with age-at-onset below 40) [2.85 µmol/l/h versus 3.12 µmol/l/h, p = 0.018; after controlling for batch effect, p = 0.006 (468 PD cases and 296 controls)], and when including the entire cohort (2.89 µmol/l/h versus 3.10 µmol/l/h, p = 0.040; after controlling for batch effect, p = 0.011). Because the alpha galactosidase A gene is X-linked, we stratified the analyses by sex. Among women who were non-carriers of GBA and LRRK2 G2019S mutations (PD, n = 155; control, n = 194), alpha galactosidase A activity was lower in PD compared to controls (2.77 µmol/l/h versus 3.10 µmol/l/h, p = 0.044; after controlling for a batch effect, p = 0.001). The enzymatic activity of acid sphingomyelinase, acid alpha-glucosidase and galactosylceramidase was not significantly different between PD and controls. In non-carriers, most lysosomal enzyme activities were correlated, with the strongest association in GCase, acid alpha-glucosidase, and alpha galactosidase A (Pearson correlation coefficient between 0.382 and 0.532). In a regression model with all five enzymes among non-carriers (adjusted for sex and age), higher alpha galactosidase A activity was associated with lower odds of PD status (OR = 0.54; 95% CI:0.31-0.95; p = 0.032). When LRRK2 G2019S PD carriers (n = 37) were compared to non-carriers with PD, carriers had higher GCase, acid sphingomyelinase and alpha galactosidase A activity. We conclude that alpha galactosidase A may have a potential independent role in PD, in addition to GCase.

Resource abundance and the critical transition to cooperation.

Cooperation is abundant in nature, occurring at all levels of biological complexity. Yet cooperation is continually threatened by subversion from noncooperating cheaters. Previous studies have shown that cooperation can nevertheless be maintained when the benefits that cooperation provides to relatives outweigh the associated costs. These fitness costs and benefits are not fixed properties, but can be affected by the environment in which populations reside. Here, we describe how one environmental factor, resource abundance, decisively affects the evolution of cooperative public goods production in two independent evolving systems. In the Avida digital evolution platform, populations evolved in environments with different levels of a required resource, whereas populations of Vibrio cholerae evolved in the presence of different nutrient concentrations. In both systems, cooperators and cheaters co-existed stably in resource-rich environments, whereas cheaters dominated in resource-poor environments. These two outcomes were separated by a sharp transition that occurred at a critical level of resource. These results offer new insights into how the environment affects the evolution of cooperation and highlight the challenges that populations of cooperators face when they experience environmental change.

Clinical Pharmacist Management of Bacteremia in a Community Hospital Emergency Department.

BACKGROUND: Bacteremia is a serious condition that leads to high morbidity and mortality. Data describing pharmacist involvement in the management of bacteremia in the emergency department are lacking. OBJECTIVE: To determine if pharmacist involvement in the management of bacteremia in the emergency department (ED) led to an increase in appropriate treatment of bacteremia as well as improvements in patient outcomes. METHODS: The primary outcome of this retrospective cohort study was the rate of appropriate treatment of bacteremia. Secondary outcomes included the rate of unplanned, infectious disease-related 90-day admission or readmission to the ED or hospital as well as infectious disease-related 90-day mortality. All patients seen in the ED and subsequently discharged who had a positive blood culture determined not to be a contaminant were included in the study. Patients were analyzed in 2 cohorts: those that were physician managed (107 patients) and those that were pharmacist managed (138 patients). RESULTS: In the physician-managed cohort, 50 of 107 (47%) patients were treated appropriately compared with 131 of 138 (95%) patients in the pharmacist-managed cohort ( P < 0.0001). There was also a decrease in attributable 90-day admission or readmission in pharmacist-managed patients, which occurred in 4 of 138 patients (2.9%) versus the physician-managed patient cohort in which 13 of 107 patients (12.1%) were readmitted ( P = 0.01). There was no difference in mortality between the groups ( P = 0.8337). CONCLUSION: Pharmacist involvement in the management of bacteremia in the ED was associated with higher rates of appropriate treatment and a corresponding decrease in the rates of attributable 90-day admission or readmission to the hospital or ED.

A bioluminescent Pseudomonas aeruginosa wound model reveals increased mortality of type 1 diabetic mice to biofilm infection.

OBJECTIVE: To examine how bacterial biofilms, as contributing factors in the delayed closure of chronic wounds in patients with diabetes, affect the healing process. METHOD: We used daily microscopic imaging and the IVIS Spectrum in vivo imaging system to monitor biofilm infections of bioluminescent Pseudomonas aeruginosa and evaluate healing in non-diabetic and streptozotocin-induced diabetic mice. RESULTS: Our studies determined that diabetes alone did not affect the rate of healing of full-depth murine back wounds compared with non-diabetic mice. The application of mature biofilms to the wounds significantly decreased the rate of healing compared with non-infected wounds for both non-diabetic as well as diabetic mice. Diabetic mice were also more severely affected by biofilms displaying elevated pus production, higher mortality rates and statistically significant increase in wound depth, granulation/fibrosis and biofilm presence. Introduction of a mutant Pseudomonas aeruginosa capable of producing high concentrations of cyclic di-GMP did not result in increased persistence in either diabetic or non-diabetic animals compared with the wild type strain. CONCLUSION: Understanding the interplay between diabetes and biofilms may lead to novel treatments and better clinical management of chronic wounds.

Real-World Effectiveness of Intravenous and Oral Antibiotic Stepdown Strategies for Gram-Negative Complicated Urinary Tract Infection With Bacteremia.

Background: Robust data are lacking regarding the optimal route, duration, and antibiotic choice for gram-negative bloodstream infection from a complicated urinary tract infection source (GN-BSI/cUTI). Methods: In this multicenter observational cohort study, we simulated a 4-arm registry trial using a causal inference method to compare effectiveness of the following regimens for GN-BSI/cUTI: complete course of an intravenous ß-lactam (IVBL) or oral stepdown therapy within 7 days using fluoroquinolones (FQs), trimethoprim-sulfamethoxazole (TMP-SMX), or high-bioavailability ß-lactams (HBBLs). Adults treated between January 2016 and December 2022 for Escherichia coli or Klebsiella species GN-BSI/cUTI were included. Propensity weighting was used to balance characteristics between groups. The 60-day recurrence was compared using a multinomial Cox proportional hazards model with probability of treatment weighting. Results: Of 2571 patients screened, 759 (30%) were included. Characteristics were similar between groups. Compared with IVBLs, we did not observe a difference in effectiveness for FQs (adjusted hazard ratio, 1.09 [95% confidence interval, .49-2.43]) or TMP-SMX (1.44 [.54-3.87]), and the effectiveness of TMP-SMX/FQ appeared to be optimal at durations of >10 days. HBBLs were associated with nearly 4-fold higher risk of recurrence (adjusted hazard ratio, 3.83 [95% confidence interval, 1.76-8.33]), which was not mitigated by longer treatment durations. Most HBBLs (67%) were not optimally dosed for bacteremia. Results were robust to multiple sensitivity analyses. Conclusions: These real-world data suggest that oral stepdown therapy with FQs or TMP-SMX have similar effectiveness as IVBLs. HBBLs were associated with higher recurrence rates, but dosing was suboptimal. Further data are needed to define optimal dosing and duration to mitigate treatment failures.

Oral ß-Lactams, Fluoroquinolones, or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Uncomplicated Escherichia coli or Klebsiella Species Bacteremia From a Urinary Tract Source.

Background: Fluoroquinolones (FQs) are effective for oral step-down therapy for gram-negative bloodstream infections but are associated with unfavorable toxic effects. Robust data are lacking for trimethoprim-sulfamethoxazole (TMP-SMX) and high-bioavailability ß-lactams (HBBLs). Methods: In this multicenter observational cohort study, we simulated a 3-arm registry trial using causal inference methods to compare the effectiveness of FQs, TMP-SMX, or HBBLs for gram-negative bloodstream infections oral step-down therapy. The study included adults treated between January 2016 and December 2022 for uncomplicated Escherichia coli or Klebsiella species bacteremia of urinary tract origin who were who were transitioned to an oral regimen after ≤4 days of effective intravenous antibiotics. Propensity weighting was used to balance characteristics between groups. 60-day recurrence was compared using a multinomial Cox proportional hazards model with probability of treatment weighting. Results: Of 2571 patients screened, 648 (25%) were included. Their median age (interquartile range) was 67 (45-78) years, and only 103 (16%) were male. Characteristics were well balanced between groups. Compared with FQs, TMP-SMX had similar effectiveness (adjusted hazard ratio, 0.91 [95% confidence interval, .30-2.78]), and HBBLs had a higher risk of recurrence (2.19 [.95-5.01]), although this difference was not statistically significant. Most HBBLs (70%) were not optimally dosed for bacteremia. A total antibiotic duration ≤8 days was associated with a higher recurrence rate in select patients with risk factors for failure. Conclusions: FQs and TMP-SMX had similar effectiveness in this real-world data set. HBBLs were associated with higher recurrence rates but suboptimal dosing may have contributed. Further studies are needed to define optimal BL dosing and duration to mitigate treatment failures.

Intergenerational transmission of maltreatment and psychopathology: the role of antenatal depression.

BACKGROUND: Maternal experience of childhood maltreatment and maternal antenatal depression are both associated with offspring childhood maltreatment and offspring adjustment problems. We have investigated the relative impact of maternal childhood maltreatment and exposure to depression in utero on offspring maltreatment and psychopathology. METHOD: The sample included 125 families from the South London Child Development Study. A prospective longitudinal design was used. Data on maternal childhood maltreatment, maternal antenatal depression (36 weeks of pregnancy), offspring childhood maltreatment (age 11 years) and offspring adolescent antisocial behaviour and depression (ages 11 and 16 years) were obtained from parents and offspring through clinical interview. RESULTS: Mothers who experienced childhood maltreatment were significantly more likely to be depressed during pregnancy [odds ratio (OR) 10.00]. Offspring of mothers who experienced only childhood maltreatment or only antenatal depression were no more at risk of being maltreated or having psychopathology; however, offspring of mothers who experienced both maternal childhood maltreatment and antenatal depression were exposed to significantly greater levels of childhood maltreatment and exhibited significantly higher levels of adolescent antisocial behaviour compared with offspring not so exposed. Furthermore, maternal childhood maltreatment accounted for a significant proportion of the variance in offspring childhood maltreatment in only those offspring exposed to depression in utero. CONCLUSIONS: Maternal childhood maltreatment and maternal antenatal depression are highly associated. The co-occurrence of both insults significantly increases the risk of offspring adversity. The antenatal period is an optimum period to identify vulnerable women and to provide interventions.

Outcomes of patients with bacteriuria/pyuria of clinically undetermined significance (BPCUS) treated with antibiotics in 23 community hospital emergency departments.

The optimal management of bacteriuria/pyuria of clinically undetermined significance (BPCUS) is unknown. Among 220 emergency department patients prescribed antibiotics for BPCUS, we found frequent readmissions, which were mitigated by outpatient follow-up visits. Observation and follow-up for an unknown diagnosis should be emphasized over antibiotics due to high likelihood of readmissions.

Effect of tele-COVID rounds and a tele-stewardship intervention on antibiotic use in COVID-19 patients admitted to 17 small community hospitals.

Antibiotic stewardship interventions are urgently needed to reduce antibiotic overuse in hospitalized COVID-19 patients, particularly in small community hospitals (SCHs), who often lack access to infectious diseases (ID) and stewardship resources. We implemented multidisciplinary tele-COVID rounds plus tele-antibiotic stewardship surveillance in 17 SCHs to standardize COVID management and evaluate concurrent antibiotics for discontinuation. Antibiotic use was compared in the 4 months preintervention versus 10 months postintervention. Interrupted time-series analysis demonstrated an immediate decrease in antibiotic use by 339 days of therapy/1000 COVID-19 patient days (p < .001), and an estimated 5258 antibiotic days avoided during the postintervention period. Thirty-day mortality was not significantly different, and a significant reduction in transfers was observed following the intervention (23.3% vs. 7.8%, p < .001). A novel tele-ID and tele-stewardship intervention significantly decreased antibiotic use and transfers among COVID-19 patients at 17 SCHs, demonstrating that telehealth is a feasible way to provide ID expertise in community and rural settings.

Tolerance induction during ontogeny. I. Presence of active suppression in mice rendered tolerant to human gamma-globulin in utero correlates with the breakdown of the tolerant state.

A specific state of T- and B-cell tolerance to human gamma-globulin (HGG) was induced in utero by intravenous administration of the deaggregated antigen to pregnant BALB/cCr mice. Tolerance persisted in the offspring until the 12th-wk of age and then began to gradually disappear. Suppressor cells could only be found when responsiveness to HGG ultimately appeared in the in utero-treated animals but not when they were completely unresponsives. In contrast, HGG-specific suppressors found in animals made unresponsive to HGG as adults appear to be associated with either the establishment and/or maintenance of the unresponsive state. To the extent that these experiments are consistent with natural self-tolerance to a serum protein, we conclude that active suppression is not a prerequisite from maintenance of unresponsiveness to self.

Interleukin 12 and interleukin 4 control T cell adhesion to endothelial selectins through opposite effects on alpha1, 3-fucosyltransferase VII gene expression.

The alpha1,3-fucosyltransferase, FucT-VII, is crucial for the formation of ligands for all three selectins, and its expression regulates the synthesis of these ligands. Short-term polarized T helper (Th)1, but not Th2 or naive CD4(+) T cells, can home to sites of inflammation, but the molecular basis for this difference has remained unclear. Here we show that naive CD4(+) T cells do not express FucT-VII and fail to bind vascular selectins. We also show that when CD4(+) T cells are activated in the presence of the Th1 polarizing cytokine interleukin (IL)-12, levels of FucT-VII mRNA and binding to E- and P-selectin are significantly augmented. In contrast, activation of CD4(+) T cells in the presence of IL-4, a Th2 polarizing cytokine, inhibited FucT-VII expression and binding to vascular selectins. T cell activation upregulated expression of the Core2 transferase, C2GnT, equivalently regardless of the presence or absence of polarizing cytokines. These data indicate that the selective ability of Th1 cells, as opposed to Th2 cells or naive CD4(+) T cells, to recognize vascular selectins and home to sites of inflammation is controlled principally by the expression of a single gene, FucT-VII.

Interleukin 2 receptor-targeted cytotoxicity. Interleukin 2 receptor-mediated action of a diphtheria toxin-related interleukin 2 fusion protein.

The IL-2 toxin-mediated inhibition of protein synthesis in high affinity IL-2-R-positive murine and human T cell lines has been examined. Both excess free IL-2 and mAb to the Tac epitope of the p55 subunit of IL-2-R are shown to block the action of IL-2 toxin; whereas, agents that interact with other receptors or antigens on the T cell surface have no effect. We show that IL-2 toxin, like diphtheria toxin, must pass through an acidic vesicle in order to intoxicate target T cells. Finally, we demonstrate that the IL-2 toxin-mediated inhibition of protein synthesis in both human and murine T cells that bear the high affinity IL-2-R is due to the classic diphtheria toxin fragment A-catalyzed ADP ribosylation of elongation factor 2.