Summary
In homeostasis of adult vertebrate tissues, stem cells are thought to self-renew by infrequent and asymmetric divisions that generate another stem cell daughter and a progenitor daughter cell committed to differentiate. This model is based largely on in vivo invertebrate or in vitro mammal studies. Here we examine the dynamic behaviour of adult hair follicle stem cells in their normal setting by employing mice with repressible H2B-GFP expression to track cell divisions and Cre inducible mice to perform long-term single cell lineage tracing. We provide direct evidence for the infrequent stem cell division model in intact tissue. Moreover, we find that differentiation of progenitor cells occurs at different times and tissue locations than self-renewal of stem cells. Distinct fates of differentiation or self-renewal are assigned to individual cells in a temporal-spatial manner. We propose that large clusters of tissue stem cells behave as populations, whose maintenance involves unidirectional daughtercell fate decisions.
Sex hormone-binding globulin (SHBG), a plasma protein that binds androgens and estrogens, also participates in the initial steps of a membrane-based steroid signaling pathway in human prostate and breast. We have recently shown that SHBG is expressed at the mRNA and protein levels in the prostate and breast. In this study, we addressed whether locally expressed SHBG: (1) Functions to regulate activation of membrane-based steroid signaling and (2) influences activation of the androgen (AR) and estrogen (ER) receptors. Using microarray analysis, we identified specific genes that are influenced by SHBG expression in LNCaP and MCF-7 cells in a manner consistent with each of these properties. These findings suggest that locally expressed SHBG can play a functional role in the steroid responsiveness of prostate and breast cells through multiple signaling pathways and that perturbations in local SHBG expression could contribute to prostate and breast cancer.
Background: Histoplasma capsulatum is the most common endemic mycosis in the United States and frequently presents as an opportunistic infection in immunocompromised hosts. Though liver involvement is common in disseminated histoplasmosis, primary gastrointestinal histoplasmosis of the liver in absence of lung involvement is rare. Similarly, cholestatic granulomatous hepatitis in liver histoplasmosis is rarely seen. Case presentation: We present a rare case of primary gastrointestinal histoplasmosis manifesting with acute granulomatous hepatitis and cholestasis in a 48-year-old female with psoriatic arthritis, receiving methotrexate and infliximab. The epidemiology, risk factors, clinical presentation, diagnosis, and treatment of histoplasmosis is discussed. Furthermore, we review the published cases of biopsy-proven disseminated histoplasmosis with cholestatic jaundice to highlight histoplasmosis involvement in the liver. Conclusion: Histoplasmosis should be considered in immunosuppressed patients with fever, chills, abdominal pain and cholestasis with progressive jaundice, particularly in subjects without evidence of biliary obstruction. Future studies are needed to accurately assess the risk of this fungal infection, specifically in patients on immunomodulatory therapy for autoimmune disease.
INTRODUCTION:
Bouveret syndrome is a rare complication of cholelithiasis. Traditional treatment has been surgical, but endoscopic therapy has emerged as an attractive option, especially in surgically unfit patients.
CASE DESCRIPTION/METHODS:
An 80-year-old female with history of coronary artery disease/CABG on Clopidogrel and COPD on home oxygen presented with severe right upper-quadrant abdominal pain and nausea for 3 days. WBC was 14,400 μ/L, afebrile, with stable vital signs. Liver tests were normal. Abdominal ultrasound showed cholelithiasis and an obstructive calcified shadow at the pylorus. CT abdomen revealed a dilated stomach, gallstones and a 3 cm gallstone in the duodenal bulb with entero-biliary fistula. Endoscopic treatment of Bouveret was planned. At endoscopy, an unexpected high-grade mid-esophageal stricture prevented passage of standard and ultra-thin gastroscopes. A 8 mm balloon dilation was performed causing a modest-sized mucosal rent. An ultrathin gastroscope (5.9 mm) was then passed through the esophageal stricture and to the duodenum. A large pigmented gallstone was encountered in the duodenal bulb with luminal occlusion. Saline solution was infused and electrohydraulic lithotripsy (EHL) was performed at escalating settings up to 100W/ 20 shots per activation. The stone was ultimately fragmented and luminal patency restored. An ulcer with a visible vessel was seen at anterior wall of duodenal bulb; brisk bleeding was noted and hemostasis was achieved with epinephrine spray and 18 W cautery using pediatric snare tip, due to limitations of a 2.0 mm endoscope channel. The entero-biliary fistula was cannulated with the ultrathin endoscope and an additional large pigmented stone was seen in the gallbladder. This was left undisturbed. The patient had an uneventful recovery and was discharged home on regular diet after 2 days.
DISCUSSION:
Endoscopic management of Bouveret syndrome is an effective intervention and should be preferred in patients with severe comorbidities. This case demonstrates how anatomic and device related challenges were overcome using an ultrathin gastroscope to manage Bouveret syndrome and luminal bleeding. An ultrathin endoscope successfully permitted performance of EHL, evaluation of cholecystoduodenal fistula and hemostasis to save the day in this complex clinical scenario.
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