Thalidomide-Related Eosinophilic Pneumonia: A case report and brief literature review

Thalidomide has regained value in the multimodality treatment of leprosy, multiple myeloma, prostate, ovarian and renal cancer. Complications related to arterial and venous complications are well described. However, pulmonary complications remain relatively uncommon. The most common pulmonary side-effect reported is non-specific dyspnea. We report a patient with multiple myeloma, who developed an eosinophilic pneumonia, shortly after starting thalidomide. She had complete resolution of her symptoms and pulmonary infiltrates on discontinuation of the drug and treatment with corticosteroids. Physicians should be cognizant of this potential complication in patients receiving thalidomide who present with dyspnea and pulmonary infiltrates

Draft genomes of gammaproteobacterial methanotrophs isolated from terrestrial ecosystems

Genome sequences of Methylobacter luteus, Methylobacter whittenburyi, Methylosarcina fibrata, Methylomicrobium agile, and Methylovulum miyakonense were generated. The strains represent aerobic methanotrophs typically isolated from various terrestrial ecosystems

A multivariate approach to aggression and the orbital frontal cortex in psychiatric patients

The association between orbital frontal cortex (OFC) volume and aggression was investigated in an at-risk psychiatric population. Forty-one psychiatric patients were referred for magnetic resonance imaging and a standardized psychometric assessment of aggression (Lifetime History of Aggression-Revised). Nineteen matched controls had lower levels of aggression and greater OFC volume, establishing the appropriateness of the psychiatric group for studying aggression pathophysiology. Consistent with study hypotheses, left OFC gray matter volume predicted 34% of the variance in self-reported aggression ratings. When impulsivity was not controlled for, left OFC gray matter only accounted for 26% of aggression variance, suggesting a complex relationship between impulsivity and OFC-aggression pathophysiology. Contrary to study hypotheses, right OFC gray matter volume did not predict degree of aggressive behavior. Current models do not account for lateralization, yet this may be quite important. Greater consideration should be given to laterality in OFC regulation of social/emotional behavior. Regulatory focus theory, positing two motivational systems, promotion and prevention, lateralized to the left and right hemispheres, respectively, may provide an explanatory framework for these results. Dysregulation of the left hemisphere \u27promotion\u27 motivational system may help to explain the aggressive behavior present in psychiatric populations

ERGO: Breaking Down the Wall between Human Health and Environmental Testing of Endocrine Disrupters

International audienc

Environmental health impacts of equine estrogens derived from hormone replacement therapy

Many factors have been considered in evaluations of the risk-benefit balance of hormone replacement therapy (HRT), used for treating menopausal symptoms in women, but not its potential risks for the environment. We investigated the possible environmental health implications of conjugated equine estrogens (CEEs), the most common components of HRT, including their discharge into the environment, their uptake, potency, and ability to induce biological effects in wildlife. Influents and effluents from four UK sewage treatment works (STWs), and bile of effluent-exposed fish, were screened for six equine estrogens. In vitro estrogen receptor (ER) activation assays were applied in humans and fish to compare their potencies, followed by in vivo exposures of fish to equine estrogens and evaluation of bioaccumulation, estrogenic responses, and ER gene expression. The equine estrogen equilenin (Eqn), and its metabolite 17ß-dihydroequilenin (17ß-Eqn), were detected by tandem GC-MSMS in all STW influent samples and 83% of STW effluent samples analyzed, respectively, at low concentrations (0.07-2.6 ng/L) and were taken-up into effluent-exposed fish. As occurs in humans, these estrogens bound to and activated the fish ERs, with potencies at ERa 2.4-3490% of that for 17ß-estradiol. Exposure of fish for 21 days to Eqn and 17ß-Eqn induced estrogenic responses including hepatic growth and vitellogenin production at concentrations as low as 0.6-4.2 ng/L. Associated with these effects were inductions of hepatic ERa and ERß1 gene expression, suggesting ER-mediated mechanism(s) of action. These data provide evidence for the discharge of equine estrogens from HRT into the aquatic environment and highlight a strong likelihood that these compounds contribute to feminization in exposed wildlife

Two Protocols to Study the Interactions of Thyroid Hormone Receptors with Other Proteins and Chromatin

International audienceUnderstanding the transcriptional function of thyroid hormone receptors implies a precise analysis of their interactions with chromatin and other protein components of the cells. We present here two protocols that are routinely used in our laboratory. The first co-immunoprecipitation procedure allows addressing the capacity of proteins to form stable multiprotein complexes with TRs in cells. The chromatin affinity purification enables us to define the sites occupied by TRs on chromatin. In this case the lack of high quality antibodies is circumvented by introducing an N-terminal tag in TR, with unspecific affinity for immunoglobulins

Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations

Background: Gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) cause susceptibility to a range of infections, autoimmunity, immune dysregulation, and combined immunodeficiency. Disease manifestations can be mild or severe and life-threatening. Hematopoietic stem cell transplantation (HSCT) has been used in some patients with more severe symptoms to treat and cure the disorder. However, the outcome of HSCT for this disorder is not well established. Objective: We sought to aggregate the worldwide experience of HSCT in patients with GOF-STAT1 mutations and to assess outcomes, including donor engraftment, overall survival, graft-versus-host disease, and transplant-related complications. Methods: Data were collected from an international cohort of 15 patients with GOF-STAT1 mutations who had undergone HSCT using a variety of conditioning regimens and donor sources. Retrospective data collection allowed the outcome of transplantation to be assessed. In vitro functional testing was performed to confirm that each of the identified STAT1 variants was in fact a GOF mutation. Results: Primary donor engraftment in this cohort of 15 patients with GOF-STAT1 mutations was 74%, and overall survival was only 40%. Secondary graft failure was common (50%), and posttransplantation event-free survival was poor (10% by 100 days). A subset of patients had hemophagocytic lymphohistiocytosis before transplant, contributing to their poor outcomes. Conclusion: Our data indicate that HSCT for patients with GOF-STAT1 mutations is curative but has significant risk of secondary graft failure and death

Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations

Background: Gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) cause susceptibility to a range of infections, autoimmunity, immune dysregulation, and combined immunodeficiency. Disease manifestations can be mild or severe and life-threatening. Hematopoietic stem cell transplantation (HSCT) has been used in some patients with more severe symptoms to treat and cure the disorder. However, the outcome of HSCT for this disorder is not well established. Objective: We sought to aggregate the worldwide experience of HSCT in patients with GOF-STAT1 mutations and to assess outcomes, including donor engraftment, overall survival, graft-versus-host disease, and transplant-related complications. Methods: Data were collected from an international cohort of 15 patients with GOF-STAT1 mutations who had undergone HSCT using a variety of conditioning regimens and donor sources. Retrospective data collection allowed the outcome of transplantation to be assessed. In vitro functional testing was performed to confirm that each of the identified STAT1 variants was in fact a GOF mutation. Results: Primary donor engraftment in this cohort of 15 patients with GOF-STAT1 mutations was 74%, and overall survival was only 40%. Secondary graft failure was common (50%), and posttransplantation event-free survival was poor (10% by 100 days). A subset of patients had hemophagocytic lymphohistiocytosis before transplant, contributing to their poor outcomes. Conclusion: Our data indicate that HSCT for patients with GOF-STAT1 mutations is curative but has significant risk of secondary graft failure and death