No abstract

Eosinophilic pneumonia is characterized by cough, lung infiltrates on imaging, and by the presence of eosinophils in the alveoli and pulmonary interstitium. Azacitidine, a pyramidine nucleoside analog of cytidine, is FDA approved for the treatment of various myelodysplastic syndromes. We present a case of a 76-year-old man with recently diagnosed myelodysplastic syndrome, who developed eosinophilic pneumonia after initiating therapy with azacitidine. There was clinical and radiographic improvement with cessation of the drug and treatment with prednisone. Diagnosis of drug-induced eosinophilic pneumonia is established by having a temporal relationship between onset of symptoms and initiation of therapy, bronchoalveolar lavage or lung biopsy evidence of pulmonary eosinophilia, no other explanation for the disease, and improvement upon cessation of the offending agent. Our case illustrates the need for a high index of suspicion to identify adverse pulmonary reactions associated with newly developed medications.

Objective Our previous study demonstrated that granulocyte-colony stimulating factor (G-CSF)-induced neuroprotection is accompanied by an inhibition of corticosterone production in a neonatal hypoxic-ischemic (HI) rat model. The present study investigates how G-CSF inhibits corticosterone production, using adrenal cortical cells and HI rat pups. Methods Cholera toxin was used to induce corticosterone synthesis in a rodent Y1 adrenal cortical cell line by increasing cyclic adenosine monophosphate (cAMP). Both corticosterone and cAMP were quantitatively measured using a commercial enzyme-linked immunosorbent assay (ELISA). The downstream signaling components of the G-CSF receptor, including Janus Kinase 2 (JAK2)/Phosphatidylinositol-3-kinase (PI3K)/Protein kinase B (Akt) and Phosphodiesterase 3B (PDE3B), were detected by western blot. Sprague-Dawley rat pups at the age of 10 days (P10) were subjected to unilateral carotid artery ligation followed by hypoxia for 2.5 hours. Brain infarction volumes were determined using 2,3,5-triphenyltetrazoliumchloride monohydrate (TTC) staining. Results G-CSF at 30ng/ml inhibited corticosterone synthesis but lost its inhibitory effect at higher doses. The inhibitory effect of G-CSF was conferred by interfering with cAMP signaling via the activation of the JAK2/PI3K/PDE3B signaling pathway. The degradation of cAMP by G-CSF signaling reduced corticosterone production. This mechanism was further verified in the neonatal HI brain injury rat model, in which inhibition of PDE3B reversed the protective effects of G-CSF. Conclusion Our data suggest that the neuroprotective G-CSF reduces corticosterone synthesis at the adrenal level by degrading intracellular cAMP via activation of the JAK2/PI3K/PDE3B pathway.

Ovarian cancer is a heterogeneous disease having the highest gynecologic fatality in the United States with a 5-year survival rate of 46.5%. Poor overall prognosis is mostly attributed to inadequate screening tools, and the majority of diagnoses occur at late stages of the disease. Due to genetic and biological underpinnings, ovarian high-grade serous carcinomas (HGSC) have etiologic evidence in the distal fallopian tube. Fallopian tube screening modalities are aggressively investigated, but few describe cytological characteristics of benign tubal specimens to help in the comparative detection of HGSC precursor cells. Here, we describe fimbrial cytomorphological and nuclear features of tubal specimens (n = 75) from patients clinically indicated for salpingectomy, bilateral or unilateral salpingo-oophorectomy, and hysterectomies for any diagnosis other than ovarian or peritoneal cancer. Fallopian tube histology was used as the diagnostic reference. A total of 75 samples had benign diagnoses. The benign cytological characteristics of fimbrial tubal specimens included ciliated cells in clustered arrangements with mild nuclear membrane irregularity, mild anisonucleosis, round and/or oval nuclei, hyperchromatic chromatin, and mild nuclear membrane irregularity. In contrast, none of the cytology samples had spindle-shaped nuclei, significantly marked anisonucleosis (n = 1), nor had hypochromasia as a characteristic feature. These cytological characteristics could be a potential area of distinction from HGSC precursor cells. Our study establishes cytomorphological characteristics of nonmalignant tubal cells which help underscore the importance of distinguishing malignant HGSC precursors through fimbrial brush sampling in minimally invasive approach.

No abstract