Silver-Russell syndrome in Hong Kong.

OBJECTIVES: To examine the molecular pathogenetic mechanisms, (epi)genotype-phenotype correlation, and the performance of the three clinical scoring systems-namely Netchine et al, Bartholdi et al, and Birmingham scores-for patients with Silver-Russell syndrome in Hong Kong. METHODS: This retrospective case series was conducted at two tertiary genetic clinics, the Clinical Genetic Service, Department of Health, and clinical genetic clinic in Queen Mary Hospital in Hong Kong. All records of patients with suspected Silver-Russell syndrome under the care of the two genetic clinics between January 2010 and September 2015 were retrieved from the computer database. RESULTS: Of the 28 live-birth patients with Silver-Russell syndrome, 35.7% had H19 loss of DNA methylation, 21.4% had maternal uniparental disomy of chromosome 7, 3.6% had mosaic maternal uniparental disomy of chromosome 11, and the remaining 39.3% were Silver-Russell syndrome of unexplained molecular origin. No significant correlation between (epi)genotype and phenotype could be identified between H19 loss of DNA methylation and maternal uniparental disomy of chromosome 7. Comparison of molecularly confirmed patients and patients with Silver-Russell syndrome of unexplained origin revealed that postnatal microcephaly and café-au-lait spots were more common in the latter group, and body and limb asymmetry was more common in the former group. Performance analysis showed the Netchine et al and Birmingham scoring systems had similar sensitivity in identifying Hong Kong Chinese subjects with Silver-Russell syndrome. CONCLUSION: This is the first territory-wide study of Silver-Russell syndrome in Hong Kong. The clinical features and the spectrum of underlying epigenetic defects were comparable to those reported in western populations.

Evaluation of FLT-PET-CT as an imaging biomarker of proliferation in primary breast cancer.

BACKGROUND: [(18)F]fluorothymidine (FLT) has been proposed as a positron emission tomography (PET)-imaging biomarker of proliferation for breast cancer. The aim of this prospective study was to assess the feasibility of FLT-PET-CT as a technique for predicting the response to neoadjuvant chemotherapy (NAC) in primary breast cancer and to compare baseline FLT with Ki-67. METHODS: Twenty women with primary breast cancer had a baseline FLT-PET-CT scan that was repeated before the second cycle of chemotherapy. Expression of Ki-67 in the diagnostic biopsy was quantified. From the FLT-PET-CT scans lesion maximum and mean standardised uptake values (SUVmax, SUVmean) were calculated. RESULTS: Mean baseline SUVmax was 7.3, and 4.62 post one cycle of NAC, representing a drop of 2.68 (36.3%). There was no significant association between baseline, post chemotherapy, or change in SUVmax and pathological response to NAC. There was a significant correlation between pre-chemotherapy Ki-67 and SUVmax of 0.604 (P=0.006). CONCLUSIONS: Baseline SUVmax measurements of FLT-PET-CT were significantly related to Ki-67 suggesting that it is a proliferation biomarker. However, in this series neither the baseline value nor the change in SUVmax after one cycle of NAC were able to predict response as most patients had a sizeable SUVmax reduction.

To PET or not to PET? That is the question. Staging in anal cancer.

BACKGROUND: Anal cancer is a rare tumour accounting for ∼2% of all colorectal cancers between 1997 and 2000 in the UK. Staging is still dominated by DRE (digital rectal examination), computed tomography (CT) and magnetic resonance imaging (MRI) imaging. The role of PET as a definitive modality is still emerging and there are relatively few adequate studies in the literature. METHODS: We looked at patients treated radically for anal cancer at Mount Vernon Cancer Centre (UK) between 2009 and 2010. Eighty-eight patients underwent treatment according to data-based coding records of which 46 had positron emission tomography (PET)/CT scans. Notes were unavailable for three patients. We compared staging following conventional modalities (DRE, MRI and CT) and PET/CT scans for these 43 patients. RESULTS: In 18 patients, the PET/CT stage differed from MRI. PET/CT altered the stage in 42% of patients but changes in subsequent management were not implemented. CONCLUSIONS: Our data show that PET/CT does alter staging in a significant number of cases although it did not lead to change in management under the current guidelines. Furthermore, there is agreement that PET/CT shows greater sensitivity for detection of lymph nodes and our study has demonstrated a distinct trend towards upstaging of anal cancer with PET/CT.

Can combined 18F-FDG-PET and dynamic contrast-enhanced MRI predict behavior of desmoid tumors in patients with familial adenomatous polyposis?

BACKGROUND: Desmoid tumors associated with familial adenomatous polyposis show variable behavior; about 10% grow relentlessly, resulting in severe morbidity or mortality. Investigations that could identify the minority of desmoid tumors that behave aggressively would allow these tumors to be treated early and spare the majority of patients who have more benign disease from unnecessary intervention. OBJECTIVE: The aim of this study was to investigate whether imaging the tumor metabolic-vascular phenotype by modern methods predicts growth. DESIGN: This is a prospective case series study. SETTINGS: The study was conducted at a tertiary center specializing in familial adenomatous polyposis and desmoid disease. PATIENTS: Nine patients with familial adenomatous polyposis (4 male, mean age 39 years) with desmoid tumor underwent 18F-FDG-PET and dynamic contrast-enhanced MRI. Standard MRI was repeated a year later to assess tumor growth. MAIN OUTCOME MEASURES: The primary outcome measured was the correlation between 18F-FDG-PET and dynamic contrast-enhanced MRI parameters and subsequent desmoid growth. RESULTS: Failed intravenous access precluded dynamic contrast-enhanced MRI in 1 female patient. Thirteen desmoid tumors (4 intra-abdominal, 2 extra-abdominal, 7 abdominal wall; mean area, 68 cm) were analyzed in the remaining 8 patients. Two patients died before follow-up MRI. Five tumors decreased in size, 3 increased in size, and 3 remained stable after a year. Significant correlation (Spearman rank correlation, significance at 5%) existed between maximum standardized uptake value and k(ep) (r = -0.56, p = 0.04), but not with other vascular parameters (K(trans) (r = -0.47, p = 0.09); v(e) (r = -0.11, p = 0.72); integrated area under the gadolinium-time curve at 60 seconds (r = -0.47, p = 0.10)). There was no significant difference in the maximum standardized uptake value or dynamic contrast-enhanced MRI parameters (K(trans), v(e), k(ep), integrated area under the gadolinium-time curve at 60 seconds) between the tumors that grew or decreased in size or between the tumor sites. However, vascular metabolic ratio (maximum standardized uptake value/K(trans)) was significantly different for tumor site (p = 0.001) and size (p = 0.001, 1-way ANOVA). LIMITATIONS: This investigation is limited because of its exploratory nature and small patient numbers. CONCLUSIONS: Although not predictive for tumor behavior, some correlations existed between dynamic contrast-enhanced MRI and 18F-FDG-PET parameters. Vascular metabolic ratio may provide further information on tumor behavior; however, this needs to be evaluated with further larger studies.

Investigation of dose minimisation protocol for 18F-FDG PET-CT in the management of lymphoma postchemotherapy followup.

INTRODUCTION: (18)F-FDG-PET-CT plays an important role in the management of lymphoma postchemotherapy followup. Some centres perform prechemotherapy baseline CT and postchemotherapy PETCT. With a concern of radiation burden, especially in young patients, this study aimed to assess if PETCT radiation dose could be reduced. METHODS: Retrospective analysis of 100 lymphoma patients was performed to record sites of disease on prechemotherapy CT and postchemotherapy PETCT. The potential reduction in radiation and time achieved with PETCT limited to sites of known disease identified on prechemotherapy CT was calculated. RESULTS: No FDG-uptake was seen in 72 cases. FDG uptake at known disease sites was seen in 24. Of the remaining 4, one had clinically significant pathology, a rectal adenocarcinoma. PETCT did not reveal any unexpected sites of lymphoma. Limiting PETCT to sites of known disease would have saved a mean radiation dose of 4 mSv (27.3%), with a mean time of 16 minutes. CONCLUSION: Our study suggests that young patients may benefit from reduced radiation by limiting PETCT to sites of known disease with low risk of missing significant pathology. However, in older patients, with increased incidence of asymptomatic synchronous malignancies, whole-body PETCT is advisable unless prechemotherapy PETCT has been performed.

Effects of dietary supplementation of Sonneratia alba extract on immune protection and disease resistance in goldfish against Aphanomyces invadans.

A 30-day study was conducted on the effects of diets supplementation with 0, 1.0%, 3.0%, and 5.0% Sonneratia alba leaf extracts on healthy goldfish, Carassius auratus against Aphanomyces invadans. Results showed that the numbers of white blood cell significantly increased in the infected fish fed with 3.0% and 5.0% supplementation diets after the second week of experiments. Whilst the numbers of red blood cell significantly decreased in the infected fish fed with 0 and 1.0% supplementation diets. After the third week of feeding trials, the total protein, albumin level and lysozyme activity were significantly increased in the infected fish fed with 3.0% and 5.0% supplementation diets. However, the myeloperoxidase activity significantly increased after two weeks in the infected fish were fed with 3.0% and 5.0% supplementation diets. The cumulative mortality rate of goldfish decreased up to 17% when the infected fish were fed with 3.0% supplementation diets. This study indicates that enriched fish feed with 3.0% and 5.0% S. alba leaf extracts enhanced the non-specific immunity and survival rate of the goldfish, suggesting that the extract may serve as a potential prophylactic treatment against A. invadans.

Reinvestment and falls in community-dwelling older adults.

BACKGROUND: Falls are common in older adults and have many adverse consequences. In an attempt to prevent further incidents, elder fallers may consciously monitor and control their movements. Ironically, conscious movement control may be one factor that contributes to disruption of automaticity of walking, increasing the likelihood of subsequent falls. OBJECTIVE: The Movement Specific Reinvestment Scale (MSRS), which aims to measure the propensity for movement-related self-consciousness and for conscious processing of movement, was used to try to discriminate elder fallers from non-fallers. METHODS: Fifty-two volunteer older adults, aged 65 or above, participated. In addition to the 10-item MSRS, participants completed the Mini-Mental State Examination questionnaire, Timed "Up & Go" test, and Four Word Short-Term Memory test. Demographics including age, gender, and history of falling were collected. RESULTS: Elder fallers scored significantly higher than non-fallers on both the movement self-consciousness and conscious motor processing components of the MSRS. Logistic regression revealed a significant association between the MSRS (conscious motor processing component) and "faller or non-faller" status. CONCLUSIONS: Elder fallers may have a higher propensity to consciously control their movements. The MSRS shows potential as a clinical tool with which to predict falls in the elderly, as well as to gain insight into the perception of safety during walking in any impaired patient.

BACCHUS: A randomised non-comparative phase II study of neoadjuvant chemotherapy (NACT) in patients with locally advanced rectal cancer (LARC).

BACKGROUND: Chemoradiation (CRT) or short-course radiotherapy (SCRT) are standard treatments for locally advanced rectal cancer (LARC). We evaluated the efficacy/safety of two neoadjuvant chemotherapy (NACT) regimens as an alternative prior to total mesorectal excision (TME). METHODS/DESIGN: This multi-centre, phase II trial in patients with magnetic resonance imaging (MRI) defined high-risk LARC (>cT3b, cN2+ or extramural venous invasion) randomised patients (1:1) to FOLFOX + Bevacizumab (Arm 1) or FOLFOXIRI + bevacizumab (Arm 2) every 14 days for 6 cycles prior to surgery. Patients were withdrawn if positron emission tomography (PET) standardised uptake value (SUV) after 3 cycles failed to decrease by >30% or increased compared to baseline. Primary endpoint was pathological complete response rate (pCR). Secondary endpoints included adverse events (AE) and toxicity. Neoadjuvant rectal (NAR) scores based on "T" and "N" downstaging were calculated. FINDINGS: Twenty patients aged 18-75 years were randomised. The trial stopped early because of poor accrual. Seventeen patients completed all 6 cycles of NACT. One stopped due to myocardial infarction, 1 poor response on PET (both received CRT) and 1 committed suicide. 11 patients had G3 AE, 1 G4 AE (neutropenia), and 1 G5 (suicide). pCR (the primary endpoint) was 0/10 for Arm 1 and 2/10 for Arm 2 i.e. 2/20 (10%) overall. Median NAR score was 14·9 with 5 (28%), 7 (39%), and 6 (33%) having low, intermediate, or high scores. Surgical morbidity was acceptable (1/18 wound infection, no anastomotic leak/pelvic sepsis/fistulae). The 24-month progression-free survival rate was 75% (95% CI: 60%-85%). INTERPRETATION: The primary endpoint (pCR rate) was not met. However, FOLFOXIRI and bevacizumab achieved promising pCR rates, low NAR scores and was well-tolerated. This regimen is suitable for testing as the novel arm against current standards of SCRT and/or CRT in a future trial.

Integrating Functional Analysis in the Next-Generation Sequencing Diagnostic Pipeline of RASopathies.

RASopathies are a group of heterogeneous conditions caused by germline mutations in RAS/MAPK signalling pathway genes. With next-generation sequencing (NGS), sequencing capacity is no longer a limitation to molecular diagnosis. Instead, the rising number of variants of unknown significance (VUSs) poses challenges to clinical interpretation and genetic counselling. We investigated the potential of an integrated pipeline combining NGS and the functional assessment of variants for the diagnosis of RASopathies. We included 63 Chinese patients with RASopathies that had previously tested negative for PTPN11 and HRAS mutations. In these patients, we performed a genetic analysis of genes associated with RASopathies using a multigene NGS panel and Sanger sequencing. For the VUSs, we evaluated evidence from genetic, bioinformatic and functional data. Twenty disease-causing mutations were identified in the 63 patients, providing a primary diagnostic yield of 31.7%. Four VUSs were identified in five patients. The functional assessment supported the pathogenicity of the RAF1 and RIT1 VUSs, while the significance of two VUSs in A2ML1 remained unclear. In summary, functional analysis improved the diagnostic yield from 31.7% to 36.5%. Although technically demanding and time-consuming, a functional genetic diagnostic analysis can ease the clinical translation of these findings to aid bedside interpretation.

Modulation of airway inflammation in cystic fibrosis. In vivo suppression of interleukin-8 levels on the respiratory epithelial surface by aerosolization of recombinant secretory leukoprotease inhibitor.

Based on the knowledge that neutrophil elastase (NE) in cystic fibrosis (CF) epithelial lining fluid (ELF) can induce human bronchial epithelial cells to express the gene for interleukin 8 (IL-8), an 8.5-kD neutrophil chemoattractant, we have evaluated CF ELF for the presence of IL-8, and investigated the ability of aerosolized recombinant secretory leukoprotease inhibitor (rSLPI) to suppress NE, and hence IL-8, levels on the respiratory epithelial surface in CF. Enzyme-linked immunoassay revealed 21.9 +/- 4.8 nM IL-8 in CF ELF compared with none in normals. Active NE was detectable in ELF of all individuals with CF and was significantly decreased (P < 0.03) after aerosolization of rSLPI. Human bronchial epithelial cells exposed to CF ELF recovered before rSLPI therapy expressed IL-8 mRNA transcripts, but ELF recovered after rSLPI therapy induced far less bronchial epithelial cell IL-8 gene expression. Consistent with this, rSLPI aerosol therapy caused a marked reduction in CF ELF IL-8 levels (P < 0.05) and neutrophil number (P < 0.02). There was also a clear association between CF ELF active NE and IL-8 levels (r = 0.94). These data suggest that rSLPI therapy not only suppresses respiratory epithelial NE levels, but also breaks a cycle of inflammation on the CF epithelial surface.

Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology.

Hypervascularity, focal necrosis, persistent cerebral edema, and rapid cellular proliferation are key histopathologic features of glioblastoma multiforme (GBM), the most common and malignant of human brain tumors. By immunoperoxidase and immunofluorescence, we definitively have demonstrated the presence of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFr) in five out of five human glioma cell lines (U-251MG, U-105MG, D-65MG, D-54MG, and CH-235MG) and in eight human GBM tumor surgical specimens. In vitro experiments with glioma cell lines revealed a consistent and reliable relation between EGFr activation and VEGF production; namely, EGF (1-20 ng/ml) stimulation of glioma cells resulted in a 25-125% increase in secretion of bioactive VEGF. Conditioned media (CM) prepared from EGF-stimulated glioma cell lines produced significant increases in cytosolic free intracellular concentrations of Ca2+ ([Ca2+]i) in human umbilical vein endothelial cells (HUVECs). Neither EGF alone or CM from glioma cultures prepared in the absence of EGF induced [Ca2+]i increases in HUVECs. Preincubation of glioma CM with A4.6.1, a monoclonal antibody to VEGF, completely abolished VEGF-mediated [Ca2+]i transients in HUVECs. Likewise, induction by glioma-derived CM of von Willebrand factor release from HUVECs was completely blocked by A4.6.1 pretreatment. These observations provide a key link in understanding the basic cellular pathophysiology of GBM tumor angiogenesis, increased vascular permeability, and cellular proliferation. Specifically, EGF activation of EGFr expressed on glioma cells leads to enhanced secretion of VEGF by glioma cells. VEGF released by glioma cells in situ most likely accounts for pathognomonic histopathologic and clinical features of GBM tumors in patients, including striking tumor angiogenesis, increased cerebral edema and hypercoagulability manifesting as focal tumor necrosis, deep vein thrombosis, or pulmonary embolism.

Reducing the blame culture through clinical audit in nuclear medicine: a mixed methods study.

OBJECTIVES: To identify the barriers and facilitators of doctors' engagement with clinical audit and to explore how and why these factors influenced doctors' decisions to engage with the NHS National Clinical Audit Programme. DESIGN: A single-embedded case study. Mixed methods sequential approach with explorative pilot study and follow-up survey. Pilot study comprised 13 semi-structured interviews with purposefully selected consultant doctors over a six-month period. Interview data coded and analysed using directed thematic content analysis with themes compared against the study's propositions. Themes derived from the pilot study informed the online survey question items. Exploratory factor analysis using STATA and descriptive statistical methods applied to summarise findings. Data triangulation techniques used to corroborate and validate findings across the different methodological techniques. SETTING: NHS National PET-CT Clinical Audit Programme. PARTICIPANTS: Doctors reporting on the Audit Programme. MAIN OUTCOME MEASURES: Extent of engagement with clinical audit, factors that influence engagement with clinical audit. RESULTS: Online survey: 58/59 doctors responded (98.3%). Audit was found to be initially threatening (79%); audit was reassuring (85%); audit helped validate professional competence (93%); participation in audit improved reporting skills (76%). Three key factors accounted for 97.6% of the variance in survey responses: (1) perception of audit's usefulness, (2) a common purpose, (3) a supportive blame free culture of trust. Factor 1 influenced medical engagement most. CONCLUSIONS: The study documents performance feedback as a key facilitator of medical engagement with clinical audit. It found that medical engagement with clinical audit was associated with reduced levels of professional anxiety and higher levels of perceived self-efficacy.

Indomethacin-induced, monocyte-dependent restoration of local graft-versus-host reaction among cells from cancer patients.

Peripheral blood mononuclear cells from 16 of 17 cancer patients known to have a negative local graft-versus-host (GVH) reaction (T-cell function deficiency) were pharmacologically immunorestored by treatment with indomethacin. The restorative effect of the indomethacin was exerted directly on nonadherent lymphocytes. This process of desuppression required for its completion the presence of glass-adherent monocytes. The immune restorative effect of indomethacin in terms of local GVH reaction did not appear to be mediated by inhibition of prostaglandin synthesis. Pharmacologic immune restoration may be an important therapeutic modality in cancer patients.

Development of a humanized disulfide-stabilized anti-p185HER2 Fv-beta-lactamase fusion protein for activation of a cephalosporin doxorubicin prodrug.

The humanized anti-p185HER2 antibody, humAb4D5-8, has completed Phase II clinical trials for p185HER2-overexpressing breast cancer. Here, this antibody is used as a building block to engineer a disulfide-linked Fv (dsFv) beta-lactamase fusion protein for use in antibody-dependent enzyme-mediated prodrug therapy using cephalosporin-based prodrugs. Three Fv variants were designed with an interchain disulfide bond buried at the VL/VH interface and secreted from Escherichia coli. One variant, dsFv3 (VL L46C VH D101C0, has similar affinity for antigen (Kd = 0.7 nM) as the wild-type Fv and was used to construct a fusion protein in which beta-lactamase, RTEM-1, is joined to the carboxy terminus of VH. The dsFv3-beta-lactamase fusion protein secreted from E. coli efficiently activates a cephalothin doxorubicin prodrug (PRODOX, kcat/km = 1.5 x 10(5) s-1 M-1). PRODOX is approximately 20-fold less toxic than free doxorubicin against breast tumor cell lines SK-BR-3 and MCF7, which express p185HER2 at elevated and normal levels, respectively. Prebinding the dsFv3-beta-lactamase fusion protein specifically enhances the toxicity level of PRODOX to that of doxorubicin against SK-BR-3 but not MCF7 cells. The fusion protein retains both antigen-binding plus kinetic activity in murine serum and is cleared rapidly as judged by pharmacokinetic analysis in nude mice (initial and terminal half-lives of 0.23 and 1.27 h, respectively). Development and characterization of the dsFv3-beta-lactamase fusion protein is an important step toward targeted prodrug therapy of p185HER2-overexpressing tumors.

Resolving the viscoelasticity and anisotropy dependence of the mechanical properties of skin from a porcine model.

The mechanical response of skin to external loads is influenced by anisotropy and viscoelasticity of the tissue, but the underlying mechanisms remain unclear. Here, we report a study of the main effects of tissue orientation (TO, which is linked to anisotropy) and strain rate (SR, a measure of viscoelasticity), as well as the interaction effects between the two factors, on the tensile properties of skin from a porcine model. Tensile testing to rupture of porcine skin tissue was conducted to evaluate the sensitivity of the tissue modulus of elasticity (E) and fracture-related properties, namely maximum stress (σU) and strain (εU) at σU, to varying SR and TO. Specimens were excised from the abdominal skin in two orientations, namely parallel (P) and right angle (R) to the torso midline. Each TO was investigated at three SR levels, namely 0.007-0.015 s(-1) (low), 0.040 s(-1) (mid) and 0.065 s(-1) (high). Two-factor analysis of variance revealed that the respective parameters responded differently to varying SR and TO. Significant changes in the σU were observed with different TOs but not with SR. The εU decreased significantly with increasing SR, but no significant variation was observed for different TOs. Significant changes in E were observed with different TOs; E increased significantly with increasing SR. More importantly, the respective mechanical parameters were not significantly influenced by interactions between SR and TO. These findings suggest that the trends associated with the changes in the skin mechanical properties may be attributed partly to differences in the anisotropy and viscoelasticity but not through any interaction between viscoelasticity and anisotropy.

Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules-the SPUtNIk study.

INTRODUCTION: Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrast-enhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently. METHODS AND ANALYSIS: The SPUtNIk study will assess the diagnostic accuracy, clinical utility and cost-effectiveness of DCE-CT, alongside the current CT and 18-flurodeoxyglucose-positron emission tomography) (18FDG-PET)-CT nodule characterisation strategies in the National Health Service (NHS). Image acquisition and data analysis for 18FDG-PET-CT and DCE-CT will follow a standardised protocol with central review of 10% to ensure quality assurance. Decision analytic modelling will assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs. ETHICS AND DISSEMINATION: Approval has been granted by the South West Research Ethics Committee. Ethics reference number 12/SW/0206. The results of the trial will be presented at national and international meetings and published in an Health Technology Assessment (HTA) Monograph and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN30784948; Pre-results.

Inflammatory pseudotumour of the neck with multifocal sites on positron emission tomography scan imaging.

We present a patient with an inflammatory pseudotumour of the neck with multifocal sites in the head and chest responding to steroids. A review of the literature revealed that this is the first case of a pseudotumour with multiple sites in the head and neck as revealed by 2-[18]fluorodeoxyglucose (FDG) PET scan imaging.

Binding of cynomolgus monkey IgE to a humanized anti-human IgE antibody and human high affinity IgE receptor.

Antibodies which block IgE binding to its high affinity receptor have the therapeutic potential for treating allergic diseases. A humanized anti-human IgE antibody (E25) was developed for this purpose. Cynomolgus monkeys were used for preclinical studies of E25. We studied the binding of purified human IgE and cynomolgus monkey IgE to E25 and the human high affinity IgE receptor alpha-chain-IgG fusion molecule (Fc epsilon RI-IgG) by surface plasmon resonance. Human IgE and cynomolgus monkey IgE bound to immobilized E25 with similar affinity (apparent Kd = 0.06 and 0.19 nM, respectively). Human IgE and cynomolgus monkey IgE also bound to immobilized Fc epsilon RI-IgG with similar affinity (apparent Kd = 0.28 and 0.30 nM, respectively). These data suggest that the cynomolgus monkey is a valid model for preclinical studies of the E25 antibody and probably for other antibodies which block IgE binding to its receptor. An enzyme-linked immunosorbent assay (ELISA) for measuring cynomolgus monkey IgE was developed to support preclinical studies. This ELISA used FcERI-IgG for capture and peroxidase labelled goat polyclonal antibody to human IgE for detection. Using purified cynomolgus monkey IgE as the standard, the serum IgE levels in six cynomolgus monkeys measured were 4-23 micrograms/ml.