Herbivory in the previous generation primes plants for enhanced insect resistance.

Inducible defenses, which provide enhanced resistance after initial attack, are nearly universal in plants. This defense signaling cascade is mediated by the synthesis, movement, and perception of jasmonic acid and related plant metabolites. To characterize the long-term persistence of plant immunity, we challenged Arabidopsis (Arabidopsis thaliana) and tomato (Solanum lycopersicum) with caterpillar herbivory, application of methyl jasmonate, or mechanical damage during vegetative growth and assessed plant resistance in subsequent generations. Here, we show that induced resistance was associated with transgenerational priming of jasmonic acid-dependent defense responses in both species, caused caterpillars to grow up to 50% smaller than on control plants, and persisted for two generations in Arabidopsis. Arabidopsis mutants that are deficient in jasmonate perception (coronatine insensitive1) or in the biogenesis of small interfering RNA (dicer-like2 dicer-like3 dicer-like4 and nuclear RNA polymerase d2a nuclear RNA polymerase d2b) do not exhibit inherited resistance. The observation of inherited resistance in both the Brassicaceae and Solanaceae suggests that this trait may be more widely distributed in plants. Epigenetic resistance to herbivory thus represents a phenotypically plastic mechanism for enhanced defense across generations.

Differential effects of indole and aliphatic glucosinolates on lepidopteran herbivores.

Glucosinolates are a diverse group of defensive secondary metabolites that is characteristic of the Brassicales. Arabidopsis thaliana (L.) Heynh. (Brassicaceae) lines with mutations that greatly reduce abundance of indole glucosinolates (cyp79B2 cyp79B3), aliphatic glucosinolates (myb28 myb29), or both (cyp79B2 cyp79B3 myb28 myb29) make it possible to test the in vivo defensive function of these two major glucosinolate classes. In experiments with Lepidoptera that are not crucifer-feeding specialists, aliphatic and indole glucosinolates had an additive effect on Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae) larval growth, whereas Trichoplusia ni (Hübner) (Lepidoptera: Noctuidae) and Manduca sexta (L.) (Lepidoptera: Sphingidae) were affected only by the absence of aliphatic glucosinolates. In the case of two crucifer-feeding specialists, Pieris rapae (L.) (Lepidoptera: Pieridae) and Plutella xylostella (L.) (Lepidoptera: Plutellidae), there were no major changes in larval performance due to decreased aliphatic and/or indole glucosinolate content. Nevertheless, choice tests show that aliphatic and indole glucosinolates act in an additive manner to promote larval feeding of both species and P. rapae oviposition. Together, these results support the hypothesis that a diversity of glucosinolates is required to limit the growth of multiple insect herbivores.

The effect of single and combined activating killer immunoglobulin-like receptor genotypes on cytomegalovirus infection and immunity after hematopoietic cell transplantation.

It has been shown that activating killer Ig-like receptor (aKIR) genes are important for control of cytomegalovirus (CMV) reactivation after hematopoietic cell transplantation (HCT). To date, using the broad classification of KIR haplotypes A and B, the precise role of individual KIR genes in the control of infection cannot be discerned. To address this, a consecutive case series of 211 non-T cell-depleted HCT patients all at risk for CMV were monitored biweekly for CMV DNA in plasma by quantitative polymerase chain reaction (Q-PCR) and at intervals for CMV-specific T cell immunity. Comparing patients with CMV reactivation (n = 152) to those with no reactivation (n = 59), the presence of specific aKIR haplotypes in the donor, but not in the recipient, were associated with protection from CMV reactivation and control of peak plasma CMV DNA (P < .001). A donor aKIR profile, predictive for low risk of CMV reactivation, contained either aKIR2DS2 and aKIR2DS4 or had >/=5 aKIR genes. Neither donor nor recipient inhibitory KIR (iKIR) played a role in a protective effect. CD4(+)- and CD8(+)-specific CMV immunity did not explain reduced CMV infection. The initial control of CMV infection after HCT is managed by aKIR functions, and donor aKIR haplotypes deserve further evaluation in donor selection for optimized HCT outcome.

Non-volatile intact indole glucosinolates are host recognition cues for ovipositing Plutella xylostella.

The diamondback moth (Plutella xylostella), a crucifer-specialist pest, has been documented to employ glucosinolates as host recognition cues for oviposition. Through the use of mutant Arabidopsis thaliana plants, we investigated the role of specific classes of glucosinolates in the signaling of oviposition by P. xylostella in vivo. Indole glucosinolate production in A. thaliana was found to be crucial in attracting oviposition. Additionally, indole glucosinolates functioned as oviposition cues only when in their intact form. 4-Methoxy-indol-3-ylmethylglucosinolate was implicated as an especially strong oviposition attractant in vitro, suggesting that indole glucosinolate secondary structure may play a role in P. xylostella host recognition as well. Aliphatic glucosinolate-derived breakdown products were found to attract P. xylostella, but only after damage or in the absence of indole glucosinolates. Furthermore, mutant plants lacking both intact indole glucosinolates and aliphatic glucosinolate breakdown products exhibited decreased oviposition attractiveness beyond that of the progenitor mutants lacking either component of the glucosinolate-myrosinase system. Therefore, we conclude that nonvolatile indole glucosinolates and volatile aliphatic glucosinolate breakdown products both appear to play important roles as host recognition cues for P. xylostella oviposition.

Impact of graft cell dose on transplant outcomes following unrelated donor allogeneic peripheral blood stem cell transplantation: higher CD34+ cell doses are associated with decreased relapse rates.

Peripheral blood stem cells (PBSC) have been increasingly used in the matched unrelated donor (MUD) transplant setting, but the impact of CD34(+) cell dose on outcomes in this setting have not been well characterized. We analyzed 181 consecutive patients who underwent MUD-PBSC transplantation at the City of Hope between August 2000 to December 2004. Patients were conditioned with either full-intensity regimen or reduced-intensity regimen. There was a significant inverse relationship between higher CD34(+) cell dose and faster neutrophil engraftment (r = -0.16, P = .035). By univariate analysis, a CD34(+) cell dose > or =4.2 x 10(6)/kg (above the lowest quartile) was associated with significantly lower relapse risk (hazard ratio [HR] = 0.67, P = .0126), with a trend for corresponding improvement for disease-free survival (HR = 0.84, P = .12) but not overall survival (HR = 0.91, P = .46). The impact of the CD34(+) cell dose remained significant in multivariate analysis. The higher CD34(+) cell dose was significantly associated with faster recovery of absolute lymphocyte counts on day +30 posttransplant. Subset analysis demonstrated that the higher CD34(+) cell dose was associated with (1) greater reduction in relapse in myeloid malignancies than that in lymphoid malignancies, (2) greater reduction in reduced-intensity conditioning than in full-intensity conditioning, (3) greater reduction in relapse when there is a inhibitory killer-cell immunoglobulin-like receptor ligand (iKIRL)-mismatch in the gravft-versus-host (GVH) direction, and (4) greater reduction in relapse when there is a lack of iKIRL, suggesting that the protective effect of CD34(+) cell dose against relapse may be immune-mediated, possibly through NK cell recovery.

Reducing Variability of Radiation Dose in CT: The New Frontier in Patient Safety.

PURPOSE: Although reducing radiation dose in CT examinations is an important goal, also important in the management of radiation dose is ensuring consistency of dose administered for a given type of examination. We have implemented an approach to reducing variance in CT radiation dose by standardizing protocols and implementing software that decreases variance. METHODS: A multifaceted approach to reducing variance in CT radiation dose was utilized: (1) establishment of the Radiation Dose Optimization Committee, (2) standardization of protocols, and (3) implementation of scanner software. Two periods of data were collected: pre-intervention (January 1, 2013, to July 31, 2014) and postintervention (January 1, 2016, to December 31, 2016). The period from August 1, 2014, to December 31, 2015, represented the time the major interventions were performed. RESULTS: The average radiation dose for all CT exams performed during the pre-intervention period (n = 39,314) was 22.3 CTDIvol with an SD of 17.0. The average radiation dose for all CT exams performed during the postintervention period (n = 49,863) was 13.6 CTDIvol with an SD of 9.01. The postintervention variance was significantly decreased (P < .0001). CONCLUSIONS: A significant decrease in the variability of our network CT radiation dose was achieved as a result of a combination of standardizing protocols across the network and implementation of advanced software that effectively managed radiation dose, all overseen by the Radiation Dose Optimization Committee.

Endoscopic cauterization of congenital pyriform fossa sinus tracts: an 18-year experience.

IMPORTANCE: Congenital pyriform fossa sinus tracts predispose to neck masses and neck abscesses in pediatric and occasionally adult patients. Traditional management involves open excision with substantial potential morbidity. Endoscopic management allows an alternative, less morbid treatment approach. OBJECTIVE: To evaluate the long-term effectiveness of endoscopic cauterization as definitive treatment for pyriform fossa sinus tracts. DESIGN, SETTING, AND PATIENTS: Retrospective review of the medical records of 23 children (aged 7 months to 14 years) with pyriform fossa sinus tracts treated with endoscopic cauterization between 1995 and 2013 at a tertiary care children's hospital. INTERVENTION: Endoscopic electrocauterization of pyriform fossa sinus tract opening. MAIN OUTCOMES AND MEASURES: Recurrence of symptoms after endoscopic treatment. RESULTS: Twenty-one of 23 patients experienced no recurrence after their first endoscopic electrocauterization of the sinus tract. The 2 patients with recurrence experienced symptoms within 1 month of cauterization and were treated with either open excision or recauterization. Endoscopic cauterization was able to definitively treat 9 patients whose treatments with incision and drainage or open excision had failed. Mean (range) follow-up for the 15 patients with follow-up was 7.4 (0.10-14.2) years. No procedure-related morbidity was reported. CONCLUSIONS AND RELEVANCE: Endoscopic cauterization seems to be an effective and potentially permanent treatment for congenital pyriform fossa sinus tracts.

In vivo optical imaging of folate receptor-ß in head and neck squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: Folate receptor (FR) expression, although known to be elevated in many types of cancer and inflammatory cells, has not been well characterized in head and neck squamous cell carcinoma (HNSCC). We hypothesized that tumor infiltrating inflammatory cells expressing FR-ß could allow fluorescent visualization of HNSCC tumors using folate conjugated dyes even when FR expression in cancer cells is low. STUDY DESIGN: Retrospective review of clinical pathologic specimens and in vivo animal study. METHODS: A tissue microarray with tumor and tumor-free tissue from 22 patients with HNSCC was stained with antibodies to FR-α and FR-ß. We characterized FR-ß(+) cells by examining CD45, CD68, CD206, and transforming growth factor (TGF)-ß expression. To investigate fluorescent imaging, mice with orthotopic tumor xenografts were imaged in vivo after intravenous injections of folate conjugated fluorescein isothiocyanate (folate-FITC) and were histologically evaluated ex vivo. RESULTS: All tumor samples demonstrated significant FR-ß staining and negligible FR-α staining. FR-ß(+) cells found in tumors coexpressed CD68 and had increased expression of CD206 and TGF-ß characteristic of tumor-associated macrophages. In the xenograft models, tumors showed strong in vivo fluorescence after folate-FITC injection in contrast to surrounding normal tissues. Histologic examination of the xenograft tissue similarly showed folate-FITC uptake in areas of inflammatory cellular infiltrate. CONCLUSIONS: Although HNSCC tumor cells do not express FR, HNSCC tumors contain a significant population of FR-ß-expressing macrophages. Folate conjugated fluorescent dye is able to specifically target and label tumor xenografts to permit macroscopic fluorescence imaging due to FR-ß expression on the infiltrating inflammatory cells.

Detrimental effect of natural killer cell alloreactivity in T-replete hematopoietic cell transplantation (HCT) for leukemia patients.

In hematopoietic cell transplantation (HCT), natural killer cell alloreactivity conferred by inhibitory ligands of killer immunoglobulin-like receptors (iKIRLs) may result in beneficial or detrimental outcomes. More data may contribute to resolution of this complex issue. We analyzed 378 primary allogeneic transplants with T-replete grafts for acute lymphoblastic leukemia (n = 101), acute myeloid leukemia and myelodysplastic syndrome (n = 149), and chronic myeloid leukemia (n = 128). The cohort was divided into 3 groups: in group 1, HLA class I matched at the antigen level (n = 260); in group 2, HLA class I mismatched at the antigen level (n = 57); and in group 3, HLA class I and iKIRLs mismatched (n = 61). One-year overall survival (OS) across groups 1 (59%), 2 (49%), and 3 (30%) was significantly different (P = .002). In contrast to group 2, group 3 had statistically lower OS (P = .05) and event-free survival (P = .01). Relapse and relapse-free mortality appeared to contribute to the low OS in group 3. The detrimental effect of natural killer alloreactivity was also evident when HLA-matched transplants were analyzed for patients lacking iKIRLs. One-year OS in patients lacking the HLA-Cw group 1 or 2 iKIRL was significantly lower than that in patients having the iKIRLs (55% vs 67%, n = 246, P = .01). Our observations indicate that, in T-replete unrelated HCT, iKIRL mismatches and the absence of iKIRLs confer higher risk to patients after HCT.