MDA5 signaling induces type 1 IFN- and IL-1-dependent lung vascular permeability which protects mice from opportunistic fungal infection.

Lungs balance threat from primary viral infection, secondary infection, and inflammatory damage. Severe pulmonary inflammation induces vascular permeability, edema, and organ dysfunction. We previously demonstrated that poly(I:C) (pICLC) induced type 1 interferon (t1IFN) protected mice from Cryptococcus gattii (Cg) via local iron restriction. Here we show pICLC increased serum protein and intravenously injected FITC-dextran in the lung airspace suggesting pICLC induces vascular permeability. Interestingly, pICLC induced a pro-inflammatory signature with significant expression of IL-1 and IL-6 which depended on MDA5 and t1IFN. Vascular permeability depended on MDA5, t1IFN, IL-1, and IL-6. T1IFN also induced MDA5 and other MDA5 signaling components suggesting that positive feedback contributes to t1IFN dependent expression of the pro-inflammatory signature. Vascular permeability, induced by pICLC or another compound, inhibited Cg by limiting iron. These data suggest that pICLC induces t1IFN which potentiates pICLC-MDA5 signaling increasing IL-1 and IL-6 resulting in leakage of antimicrobial serum factors into lung airspace. Thus, induced vascular permeability may act as an innate defense mechanism against opportunistic fungal infection, such as cryptococcosis, and may be exploited as a host-directed therapeutic target.

Developing and pilot testing an oral health screening tool for diabetes care providers.

BACKGROUND: People with poorly managed diabetes are at greater risk of periodontal disease. Periodontal disease that is not effectively managed can affect glycaemic levels. Diabetes care providers, including general practitioners and diabetes educators, are encouraged to promote oral health of their clients. However, valid and reliable oral health screening tools that assess the risk of poor oral health, that are easy to administer among non-dental professionals, currently do not exist. Existing screening tools are difficult to incorporate into routine diabetes consultations due to their length. Thus, this study aimed to develop and pilot a short oral health screening tool that would identify risk of existing oral diseases and encourage appropriate referrals to the dental service. METHODS: A three-item screening tool was developed after a comprehensive review of the literature and consensus from an expert panel. The tool was then piloted as part of a larger cross-sectional survey of 260 adults with diabetes who were accessing public diabetes clinics at two locations in Sydney, Australia. As part of the survey, participants completed the three-item screening tool and a 14-item validated tool, the Oral Health Impact Profile (OHIP-14), which has been used previously in the preliminary validation of screening tools. Sensitivity and specificity analyses were then undertaken comparing the results of the two tools. RESULTS: A statistically significant correlation was found between the shorter screening tool and the OHIP-14 (rho = 0.453, p < 0.001), indicating adequate validity. The three-item tool had high sensitivity (90.5%, 95% CI 84.9%, 94.7%), with a specificity of 46.3% (95% CI 37.7%, 55.2%). The negative predictive value was 81.4% (95% CI 71.3, 89.3). No single item performed as well regarding sensitivity and negative predictive value when compared to the three items collectively. CONCLUSIONS: The three-item screening tool developed was found to be valid and sensitive in identifying risk of poor oral health, requiring oral health referrals, among people with diabetes in this pilot. This is a simple, accessible tool that diabetes care providers could incorporate into their routine consultations. Further validation against comprehensive dental assessments is needed to reassess the tool's specificity and sensitivity in diverse settings.

Long-Term Effects of Developmental Exposure to Oxycodone on Gut Microbiota and Relationship to Adult Behaviors and Metabolism.

Opioid drugs are commonly prescribed analgesic to pregnant women. Direct exposure to such drugs may slow gut motility, alter gut permeability, and affect the gut microbiome. While such drugs affect gut microbiome in infants, no study to date has determined whether developmental exposure to such drugs results in longstanding effects on gut microbiota and correspondingly on host responses. We hypothesized developmental exposure to oxycodone (OXY) leads to enduring effects on gut microbiota and such changes are associated with adult neurobehavioral and metabolic changes. Female mice were treated daily with 5 mg OXY/kg or saline solution (control [CTL]) for 2 weeks prior to breeding and then throughout gestation. Male and female offspring pups were weaned, tested with a battery of behavioral and metabolic tests, and fecal boli were collected adulthood (120 days of age). In females, relative abundance of Butyricimonas spp., Bacteroidetes, Anaeroplasma spp., TM7, Enterococcus spp., and Clostridia were greater in OXY versus CTL individuals. In males, relative abundance of Coriobacteriaceae, Roseburia spp., Sutterella spp., and Clostridia were elevated in OXY exposed individuals. Bacterial changes were also associated with predictive metabolite pathway alterations that also varied according to sex. In males and females, affected gut microbiota correlated with metabolic but not behavioral alterations. The findings suggest that developmental exposure to OXY leads to lasting effects on adult gut microbiota that might affect host metabolism, possibly through specific bacterial metabolites or other bacterial-derived products. Further work is needed to characterize how developmental exposure to OXY affects host responses through the gut microbiome. IMPORTANCE This is the first work to show in a rodent model that in utero exposure to an opioid drug can lead to longstanding effects on the gut microbiota when examined at adulthood. Further, such bacterial changes are associated with metabolic host responses. Given the similarities between rodent and human microbiomes, it raises cause for concern that similar effects may become evident in children born to mothers taking oxycodone and other opioid drugs.

Applying Machine Learning Approaches to Suicide Prediction Using Healthcare Data: Overview and Future Directions.

Objective: Early identification of individuals who are at risk for suicide is crucial in supporting suicide prevention. Machine learning is emerging as a promising approach to support this objective. Machine learning is broadly defined as a set of mathematical models and computational algorithms designed to automatically learn complex patterns between predictors and outcomes from example data, without being explicitly programmed to do so. The model's performance continuously improves over time by learning from newly available data. Method: This concept paper explores how machine learning approaches applied to healthcare data obtained from electronic health records, including billing and claims data, can advance our ability to accurately predict future suicidal behavior. Results: We provide a general overview of machine learning concepts, summarize exemplar studies, describe continued challenges, and propose innovative research directions. Conclusion: Machine learning has potential for improving estimation of suicide risk, yet important challenges and opportunities remain. Further research can focus on incorporating evolving methods for addressing data imbalances, understanding factors that affect generalizability across samples and healthcare systems, expanding the richness of the data, leveraging newer machine learning approaches, and developing automatic learning systems.

Sleep and quality of life in lung cancer patients and survivors.

BACKGROUND: Lung cancer patients and survivors are vulnerable to disturbed sleep and impaired quality of life (QOL) across the continuum of illness. Few studies have sought to identify predictors of QOL using well-validated measures of both sleep quality and QOL in this population. PURPOSE: The purpose of this study was to examine factors associated with lung cancer that are predictive of QOL in adult lung cancer patients and survivors in the outpatient setting. METHOD: Cross-sectional data collected exclusively in the outpatient setting from three lung cancer clinics in the Northeastern United States were pooled and analyzed. The pooled sample (N = 103) data included cancer type and stage, body mass index, Pittsburgh Sleep Quality Index, and Functional Assessment of Cancer Treatment-Lung information. RESULTS: Significant correlations between sleep quality, lung cancer symptom severity, and QOL were observed. Sleep quality and lung cancer symptoms were found to be statistically significant predictors of QOL. No significant differences in QOL were found based on cancer type or recruitment source. Demographic factors and cancer stage were also not predictive of overall QOL. CONCLUSIONS: Lung cancer symptoms and sleep quality were important determinants of QOL in this pooled sample of lung cancer patients and survivors. IMPLICATIONS FOR PRACTICE: Patients and survivors of lung cancer require routine screening for sleep disturbance, lung cancer symptoms, and QOL needs. Nurse practitioners can help improve QOL in this population by screening for and treating sleep disturbance and lung cancer symptoms.

Maternal Oxycodone Treatment Results in Neurobehavioral Disruptions in Mice Offspring.

Opioid drugs are increasingly being prescribed to pregnant women. Such compounds can also bind and activate opioid receptors in the fetal brain, which could lead to long-term brain and behavioral disruptions. We hypothesized that maternal treatment with oxycodone (OXY), the primary opioid at the center of the current crisis, leads to later neurobehavioral disorders and gene expression changes in the hypothalamus and hippocampus of resulting offspring. Female mice were treated daily with 5 mg OXY/kg or saline solution (control; CTL) for two weeks before breeding and then throughout gestation. Male and female offspring from both groups were tested with a battery of behavioral and metabolic tests to measure cognition, exploratory-like, anxiety-like, voluntary physical activity, and socio-communication behaviors. qPCR analyses were performed for candidate gene expression patterns in the hypothalamus and hippocampus of OXY and CTL derived offspring. Developmental exposure to OXY caused socio-communication changes that persisted from weaning through adulthood. Such offspring also showed cognitive impairments, reduced voluntary physical activity, and weighed more than CTL counterparts. In the hippocampus, prenatal exposure to OXY caused sex-dependent differences in expression of genes encoding opioid receptors and those involved in serotonin signaling. OXY exposure induced changes in neuropeptide hormone expression and the epigenetic modulator, Dnmt3a, in the hypothalamus, which could result in epigenetic changes in this brain region. The findings suggest cause for concern that consumption of OXY by pregnant mothers may result in permanent neurobehavioral changes in their offspring. Further work is needed to determine the potential underpinning epigenetic mechanisms.

Alcohol Use Disorder in the Age of Technology: A Review of Wearable Biosensors in Alcohol Use Disorder Treatment.

Biosensors enable observation and understanding of latent physiological occurrences otherwise unknown or invasively detected. Wearable biosensors monitoring physiological constructs across a wide variety of mental and physical health conditions have become an important trend in innovative research methodologies. Within substance use research, explorations of biosensor technology commonly focus on identifying physiological indicators of intoxication to increase understanding of addiction etiology and to inform treatment recommendations. In this review, we examine the state of research in this area as it pertains to treatment of alcohol use disorders specifically highlighting the gaps in our current knowledge with recommendations for future research. Annually, alcohol use disorders affect approximately 15 million individuals. A primary focus of existing wearable technology-based research among people with alcohol use disorders is identifying alcohol intoxication. A large benefit of wearable biosensors for this purpose is they provide continuous readings in a passive manner compared with the gold standard measure of blood alcohol content (BAC) traditionally measured intermittently by breathalyzer or blood draw. There are two primary means of measuring intoxication with biosensors: gait and sweat. Gait changes have been measured via smart sensors placed on the wrist, in the shoe, and mobile device sensors in smart phones. Sweat measured by transdermal biosensors detects the presence of alcohol in the blood stream correlating to BAC. Transdermal biosensors have been designed in tattoos/skin patches, shirts, and most commonly, devices worn on the ankle or wrist. Transdermal devices were initially developed to help monitor court-ordered sobriety among offenders with alcohol use disorder. These devices now prove most useful in continuously tracking consumption throughout clinical trials for behavioral treatment modalities. More recent research has started exploring the uses for physical activity trackers and physiological arousal sensors to guide behavioral interventions for relapse prevention. While research has begun to demonstrate wearable devices' utility in reducing alcohol consumption among individuals aiming to cutdown on their drinking, monitoring sustained abstinence in studies exploring contingency management for alcohol use disorders, and facilitating engagement in activity-based treatment interventions, their full potential to further aid in understanding of, and treatment for, alcohol use disorders has yet to be explored.

Disruption of global hypothalamic microRNA (miR) profiles and associated behavioral changes in California mice (Peromyscus californicus) developmentally exposed to endocrine disrupting chemicals.

Developmental exposure to endocrine disrupting chemicals (EDCs), e.g., bisphenol A (BPA) or genistein (GEN), causes longstanding epigenome effects. MicroRNAs (miRs) regulate which mRNAs will be translated to proteins and thereby serve as the final checkpoint in epigenetic control. Scant amount is known, however, whether EDCs affect neural miRNA (miR) patterns. We aimed to test the hypothesis that developmental exposure of California mice (Peromyscus californicus) to GEN, BPA, or both chemicals influences hypothalamic miR/small RNA profiles and ascertain the extent such biomolecular alterations correlate with behavioral and metabolic changes. California mice were developmentally exposed to GEN (250 mg/kg feed weight, FW), GEN (250 mg/kg FW)+BPA (5 mg/kg FW), low dose (LD) BPA (5 mg/kg FW), or upper dose (UD) BPA (50 mg/kg FW). Adult offspring were tested in a battery of behavioral and metabolic tests; whereupon, mice were euthanized, brains were collected and frozen, small RNAs were isolated from hypothalamic punches, and subsequently sequenced. California mice exposed to one or both EDCs engaged in one or more repetitive behaviors. GEN, LD BPA, and UD BPA altered aspects of ultrasonic and audible vocalizations. Each EDC exposure led to sex-dependent differences in differentially expressed miR/small RNAs with miR7-2, miR146, and miR148a being increased in all female and male EDC exposed groups. Current findings reveal that developmental exposure to GEN and/or BPA affects hypothalamic miR/small RNA expression patterns, and such changes correlate with EDC-induced behavioral and metabolic alterations. miR146 is likely an important mediator and biomarker of EDC exposure in mammals, including humans.

Maternal oxycodone treatment causes pathophysiological changes in the mouse placenta.

INTRODUCTION: Pregnant women are increasingly being prescribed and abusing opioid drugs. As the primary communication organ between mother and conceptus, the placenta may be vulnerable to opioid effects but also holds the key to better understanding how these drugs affect long-term offspring health. We hypothesized that maternal treatment with oxycodone (OXY), the primary opioid at the center of the current crisis, deleteriously affects placental structure and gene expression patterns. METHODS: Female mice were treated daily with 5 mg OXY/kg or saline solution (Control, CTL) for two weeks prior to breeding and until placenta were collected at embryonic age 12.5. A portion of the placenta was fixed for histology, and the remainder was frozen for RNA isolation followed by RNAseq. RESULTS: Maternal OXY treatment reduced parietal trophoblast giant cell (pTGC) area and decreased the maternal blood vessel area within the labyrinth region. OXY exposure affected placental gene expression profiles in a sex dependent manner with female placenta showing up-regulation of many placental enriched genes, including Ceacam11, Ceacam14, Ceacam12, Ceacam13, Prl7b1, Prl2b1, Ctsq, and Tpbpa. In contrast, placenta of OXY exposed males had alteration of many ribosomal proteins. Weighted correlation network analysis revealed that in OXY female vs. CTL female comparison, select modules correlated with OXY-induced placental histological changes. Such associations were lacking in the male OXY vs. CTL male comparison. DISCUSSION: Results suggest OXY exposure alters placental histology. In response to OXY exposure, female placenta responds by upregulating placental enriched transcripts that are either unchanged or downregulated in male placenta. Such changes may shield female offspring from developmental origins of health and disease-based diseases.

Endocrine disruption of gene expression and microRNA profiles in hippocampus and hypothalamus of California mice: Association of gene expression changes with behavioural outcomes.

The hypothalamus and hippocampus are sensitive to early exposure to endocrine disrupting chemicals (EDCs). Two EDCs that have raised particular concerns are bisphenol A (BPA), a widely prevalent chemical in many common household items, and genistein (GEN), a phyto-oestrogen present in soy and other plants. We hypothesised that early exposure to BPA or GEN may lead to permanent effects on gene expression profiles for both coding RNAs (mRNAs) and microRNAs (miRs), which can affect the translation of mRNAs. Such EDC-induced biomolecular changes may affect behavioural and metabolic patterns. California mice (Peromyscus californicus) male and female offspring were developmentally exposed via the maternal diet to BPA (5 mg kg-1 feed weight low dose [LD] and 50 mg kg-1 feed weight upper dose [UD]), GEN (250 mg kg-1 feed weight) or a phyto-oestrogen-free diet (AIN) control. Behavioural and metabolic tests were performed at 180 days of age. A quantitative polymerase chain reacttion analysis was performed for candidate mRNAs and miRs in the hypothalamus and hippocampus. LD BPA and GEN exposed California mice offspring showed socio-communication impairments. Hypothalamic Avp, Esr1, Kiss1 and Lepr were increased in LD BPA offspring. miR-153 was elevated but miR-181a was reduced in LD BPA offspring. miR-9 and miR-153 were increased in the hippocampi of LD BPA offspring, whereas GEN decreased hippocampal miR-7a and miR-153 expression. Correlation analyses revealed neural expression of miR-153 and miR-181a was associated with socio-communication deficits in LD BPA individuals. The findings reveal a cause for concern such that developmental exposure of BPA or GEN in California mice (and potentially by translation in humans) can lead to long standing neurobehavioural consequences.

Z-Score Neurofeedback and Heart Rate Variability Training for Adults and Children with Symptoms of Attention-Deficit/Hyperactivity Disorder: A Retrospective Study.

ADHD is a common condition that causes suffering for those affected and economic loss for society at large. The current standard treatment for ADHD includes stimulant medications, which are not effective for all patients, may include side effects, and can be non-medically misused. Z-score neurofeedback (NFB) and heart rate variability (HRV) biofeedback are alternative treatment strategies that have been associated with Attention-Deficit/Hyperactivity Disorder (ADHD) symptom improvement. We utilized a retrospective pre-post study design to quantify the change in clients' ADHD symptoms after combined NFB + HRV treatment (which included simultaneous z-score training at four sites). We also assessed whether relevant physiological measures changed in accordance with the protocol, which would be consistent with effective NFB + HRV training. Adults (n = 39) and children (n = 100) with Borderline or Clinical ADHD classifications by the Achenbach System of Empirically Based Assessment (ASEBA) received 30 sessions of NFB + HRV training. Measures were compared before and after treatment for the ASEBA, the Integrated Visual and Auditory Continuous Performance Test (IVA), ADHD medication use, HRV and breathing parameters, and quantitative electroencephalogram (QEEG) parameters. Average ASEBA Attention-Deficit/Hyperactive Problems score improved after treatment for adults and children (p < 0.0001), with Cohen effect sizes (dz) of -1.21 and -1.17, respectively. 87.2% of adults and 80.0% of children experienced improvements of a magnitude greater than or equal to the Minimal Clinically Important Difference. After treatment, 70.8% of adults and 52.8% of children who began in the ASEBA Clinical range, and 80.0% of adults and 63.8% of children who began in the ASEBA Borderline range, were classified in the Normal range. IVA scores also improved after treatment. Changes in HRV and breathing pattern after treatment were consistent with the protocol. QEEG parameters after treatment were closer to the age-based normative mean, which is consistent with effective z-score NFB training.

Laparoscopic management of snare entrapment during colonoscopic polypectomy.

Colonoscopic polypectomy reduces the risk of colon cancer development by interrupting the adenoma to carcinoma progression. A variety of techniques are available to perform polypectomy including the use of forceps or snare device with or without electrocautery. While forceps polypectomy tends to be the procedure of choice for small polyps, snare polypectomy has been found to be the preferred method for removal of polyps 1 cm or greater in size. The two most common post-polypectomy complications are bleeding and perforation. Though rare in the case of polypectomy, any mechanical device used in a procedure has an inherent risk of malfunction. Here, we present a case of an attempted snare polypectomy with malfunctioning of the device, failure of endoscopic retrieval and subsequent management with laparoscopic resection of the affected segment.

Cognitive-Behavioral Therapy for Insomnia to Reduce Chronic Migraine: A Sequential Bayesian Analysis.

BACKGROUND: Insomnia is frequently comorbid with chronic migraine, and small trials suggest that cognitive-behavioral treatment of insomnia (CBTi) may reduce migraine frequency. This study endeavored to provide a quantitative synthesis of existing CBTi trials for adults with chronic migraine using Bayesian statistical methods, given their utility in combining prior knowledge with sequentially gathered data. METHODS: Completer analyses of 2 randomized trials comparing CBTi to a sham control intervention (Calhoun and Ford, 2007; Smitherman et al, 2016) were used to quantify the effects of a brief course of treatment on headache frequency. Change in headache frequency from baseline to the primary endpoint (6-8 weeks posttreatment) was regressed on group status using a Gaussian linear model with each study specified in the order of completion. To estimate the combined effect, posterior distributions from the Calhoun and Ford study were used as informative priors for conditioning on the Smitherman et al data. RESULTS: In a combined analysis of these prior studies, monthly headache frequency of the treatment group decreased by 6.2 days (95%CrI: -9.7 to -2.7) more than the control group, supporting an interpretation that there is a 97.5% chance that the treatment intervention is at least 2.7 days better than the control intervention. The analysis supports the hypothesis that at least for those who complete treatment, there is high probability that individuals who receive CBTi experience greater headache reduction than those who receive a control intervention equated for therapist time and out-of-session skills practice. CONCLUSION: Cognitive-behavioral interventions for comorbid insomnia hold promise for reducing headache frequency among those with chronic migraine. These findings add to a small but growing body of literature that migraineurs with comorbid conditions often respond well to behavioral interventions, and that targeting comorbidities may improve migraine itself.

Perceived triggers of primary headache disorders: A meta-analysis.

Objective To quantitatively synthesize extant literature on perceived triggers of primary headache disorders. Methods A meta-analytic review of headache trigger survey studies was conducted. Endorsement rates, assessment method, and headache and sample characteristics were extracted from included articles. Separate random-effects models were used to assess trigger endorsement rates and post-hoc meta-regressions examined potential moderator variables. Results 85 articles from 1958 to 2015 were included, involving 27,122 participants and querying 420 unique triggers (collapsed into 15 categories). Four-fifths (0.81; 95% CI .75 to .86) of individuals with migraine or tension-type headache endorsed at least one trigger. Rates increased with the number of categories queried (OR: 1.18, 1.08-1.30) and year of publication (OR: 1.04, 1.00-1.08). The triggers most commonly endorsed were stress (.58, .53-.63) and sleep (.41, .36-.47). Conclusions Extreme heterogeneity characterizes the headache trigger literature. Most individuals with a primary headache disorder perceive their attacks to be triggered by one or more precipitants, the most common of which are stress and sleep. However, trigger endorsement is influenced by method of assessment. Enhancing methodological consistency and prioritizing experimental studies would improve our understanding of headache triggers.

Alcohol Use as a Comorbidity and Precipitant of Primary Headache: Review and Meta-analysis.

PURPOSE OF REVIEW: In contrast to well-established relationships between headache and affective disorders, the role of alcohol use in primary headache disorders is less clear. This paper provides a narrative overview of research on alcohol use disorders (AUDs) in primary headache and presents a meta-analysis of the role of alcohol as a trigger (precipitant) of headache. RECENT FINDINGS: The majority of studies on AUDs in headache have failed to find evidence that migraine or tension-type headache (TTH) is associated with increased risk for AUDs or problematic alcohol use. The meta-analysis indicated that 22% (95% CI: 17-29%) of individuals with primary headache endorsed alcohol as a trigger. No differences were found between individuals with migraine (with or without aura) or TTH. Odds of endorsing red wine as a trigger were over 3 times greater than odds of endorsing beer. An absence of increased risk for AUDs among those with primary headache may be attributable to alcohol's role in precipitating headache attacks for some susceptible individuals. Roughly one fifth of headache sufferers believe alcohol precipitates at least some of their attacks. Considerable study heterogeneity limits fine-grained comparisons across studies and suggests needs for more standardized methods for studying alcohol-headache relationships and rigorous experimental designs.

Regulating the level of intracellular hydrogen peroxide: the role of peroxiredoxin IV.

Hydrogen peroxide (H2O2) can act as a signalling molecule affecting the cell cycle as well as contributing towards the oxidative stress response. The primary target of this molecule is oxidation-sensitive cysteine residues in proteins such as protein tyrosine phosphatases. The cell has robust mechanisms to remove H2O2 that need to be regulated for H2O2 to react with and modify protein thiols. In particular, the family of peroxiredoxins are capable of the rapid removal of even trace amounts of this molecule. It has been suggested that the inactivation of peroxiredoxins by hyperoxidation may allow H2O2 levels to increase in cells and thereby modify critical thiol groups in proteins. We have been studying how the H2O2 produced during disulfide formation in the ER (endoplasmic reticulum) is metabolized and have shown that ER-resident peroxiredoxin IV not only can remove H2O2, but also contributes to de novo disulfide formation. In the present article, we review recent data on the structure and function of this enzyme as well as its sensitivity to hyperoxidation.

Injury-induced insulin resistance in adipose tissue.

Hyperglycemia and insulin resistance are common findings in critical illness. Patients in the surgical ICU are frequently treated for this 'critical illness diabetes' with intensive insulin therapy, resulting in a substantial reduction in morbidity and mortality. Adipose tissue is an important insulin target tissue, but it is not known whether adipose tissue is affected by critical illness diabetes. In the present study, a rodent model of critical illness diabetes was used to determine whether adipose tissue becomes acutely insulin resistant and how insulin signaling pathways are being affected. There was a reduction in insulin-induced phosphorylation of IR, IRS-1, Akt and GSK-3ß. Since insulin resistance occurs rapidly in adipose tissue, but before the insulin resistance in skeletal muscle, it may play a role in the initial development of critical illness diabetes.

Identification and expression of a new type II transmembrane protein in human mast cells.

A cDNA encoding a new type II transmembrane protein has been isolated from human mast cells by subtraction cloning. This cDNA contains an open reading frame of 186 amino acids. RT-PCR analysis showed that this gene is differentially expressed in mast cells. Therefore, the peptide encoded by this gene was termed mast cell-expressed membrane protein 1 (MCEMP1). The MCEMP1 gene contains seven exons and was mapped to human chromosome 19p13.3. The epitope-tagged MCEMP1 has been expressed in mammalian cells and found to be localized to the cellular membrane with its C-terminus extending to the outside of the membrane and N-terminus into the cytoplasmic compartment. Monoclonal antibodies against MCEMP1 were generated and characterized by immunoprecipitation and FACS. The results showed that the native MCEMP1 is expressed in cord blood-derived mast cells and HMC-1 and THP-1 cell lines, but not in other cell types that we have tested. Immunochemical staining of human lung sections showed that MCEMP1 staining is specifically associated with lung mast cells.