Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity.

Receptors for basement membrane (BM) proteins, including dystroglycan (DG), coordinate tissue development and function by mechanisms that are only partially defined. To further elucidate these mechanisms, we generated a conditional knockout of DG in the epithelial compartment of the mouse mammary gland. Deletion of DG caused an inhibition of mammary epithelial outgrowth and a failure of lactation. Surprisingly, loss of DG in vivo did not disrupt normal tissue architecture or BM formation, even though cultured Dag1-null epithelial cells failed to assemble laminin-111 at the cell surface. The absence of DG was, however, associated with a marked loss in activity of signal transducer and activator of transcription 5 (STAT5). Loss of DG perturbed STAT5 signaling induced by either prolactin or growth hormone. We found that DG regulates signaling by both hormones in a manner that is dependent on laminin-111 binding, but independent of the DG cytoplasmic domain, suggesting that it acts via a co-receptor mechanism reliant on DG-mediated laminin assembly. These results demonstrate a requirement for DG in the growth and function of a mammalian epithelial tissue in vivo. Moreover, we reveal a selective role for DG in the control of multiple STAT5-dependent hormone signaling pathways, with implications for numerous diseases in which DG function is compromised.

Steroid induced atrial fibrillation.

A 72-year-old female presented with an acute flaure of Crohn's disease and received intravenous methylprednisolone. The following morning ECG showed atrial fibrillation with a rapid ventricular response of 111 bts/min, which spontaneously resolved within 7 hours. The underlying arrhythmogenenic mechanism is unknown.

Survival Prediction in Ambulatory Patients With Stage III/IV Non-Small Cell Lung Cancer Using the Palliative Performance Scale, ECOG, and Lung Cancer Symptom Scale.

OBJECTIVES: Patients with advanced non-small cell lung cancer (NSCLC) have a life expectancy of less than 1 year. Therefore, it is important to maximize their quality of life and find a tool that can more accurately predict survival. MATERIALS: The Palliative Performance Scale (PPS) is used to predict survival for patients with advanced disease based on functional dimensions. The value of the PPS in ambulatory patients with cancer has not been examined to date. The Lung Cancer Symptom Scale (LCSS) measures six major symptoms and their effect on symptomatic distress and activity. We evaluated 62 patients with stage III or IV NSCLC and Eastern Cooperative Oncology Group (ECOG) Scale Score ≥1 at baseline in a thoracic oncology clinic. In all, 62 patients had LCSS and PPS evaluated at baseline and 54 patients had 4-week follow-up using LCSS, PPS, and ECOG. RESULTS: Fifty-four patients completed baseline and follow-up. Mean age was 63.7 years. Sixty-three percent were receiving chemotherapy at evaluation. Seventeen patients died. Mean baseline measures were LCSS 6.18 (1-14); PPS 66.6 (40-90); and ECOG 1.82 (1-4). Censored survival times were calculated from enrollment of the first patient for 380 days. A proportional hazardous model was computed for survival status. Hazard ratios for death were 1.25 (P = .013) for LCSS, 2.12 (P = .027) for ECOG, and 1.02 for PPS (P = .49). CONCLUSIONS: The LCSS predicted prognosis best in this study. The PPS did not accurately predict prognosis in our patient population.

Hypotension associated with advanced hodgkin lymphoma.

Hypotension is an extremely rare manifestation of Hodgkin lymphoma. We report the case of a patient who presented with new onset hypotension and was diagnosed with urosepsis and septic shock requiring pressor support for maintaining his blood pressure. computed tomography (CT) scan of abdomen showed liver lesions, which were new on comparison with a CT abdomen done 3 weeks back. Biopsy of the liver lesions and subsequently a bone marrow biopsy showed large atypical Reed-Sternberg cells, positive for CD15 and CD 30 and negative for CD45, CD3 and CD20 on immuno-histochemical staining, hence establishing the diagnosis of Hodgkin lymphoma. The mechanism involved in Hodgkin lymphoma causing hypotension remains anecdotal, but since it is mostly seen in patients with advanced Hodgkin lymphoma, it is hypothetically related to a complex interaction between cytokines and mediators of vasodilatation. Here we review relevant literature pertaining to presentation and pathogenesis of this elusive and rare association.