Membrane Structure of Aquaporin Observed with Combined Experimental and Theoretical Sum Frequency Generation Spectroscopy.

High-resolution structural information on membrane proteins is essential for understanding cell biology and for the structure-based design of new medical drugs and drug delivery strategies. X-ray diffraction (XRD) can provide angstrom-level information about the structure of membrane proteins, yet for XRD experiments, proteins are removed from their native membrane environment, chemically stabilized, and crystallized, all of which can compromise the conformation. Here, we describe how a combination of surface-sensitive vibrational spectroscopy and molecular dynamics simulations can account for the native membrane environment. We observe the structure of a glycerol facilitator channel (GlpF), an aquaporin membrane channel finely tuned to selectively transport water and glycerol molecules across the membrane barrier. We find subtle but significant differences between the XRD structure and the inferred in situ structure of GlpF.

Familial recurrence of congenital heart diseases.

Familial recurrence of congenital heart disease (CHD), in particular, d-transposition of great arteries (d-TGA) is rare. However, there have been several reports in the literature of sibling recurrence of total anomalous pulmonary venous return (TAPVR). This is the first case report in the literature, describing mother to offspring recurrence of d-TGA. We describe two cases of non-syndromic CHD with mother to offspring and sibling recurrence. The first case is an antenatally diagnosed d-TGA on fetal echocardiogram at 25 weeks of gestational age in the offspring of a 30-year-old mother with d-TGA. The second case is a sibling reoccurrence of TAPVR diagnosed antenatally at 30 weeks of gestational age, with supradiaphragmatic TAPVR on fetal echocardiogram in a mother, whose first child was diagnosed with infradiaphragmatic TAPVR in infancy.

Sentinel lymph node dissection for prostate cancer: experience with more than 1,000 patients.

PURPOSE: We determined the incidence of positive pelvic lymph nodes in men undergoing radical retropubic prostatectomy and describe the correlation with prostate specific antigen, histological grade and stage. We examined whether tumor cells are localized in the sentinel nodes only or also in other nonsentinel lymph nodes. MATERIALS AND METHODS: A total of 1,055 men with prostate cancer underwent radio guided pelvic lymph node dissection and radical retropubic prostatectomy. In men with prostate specific antigen 20 ng/ml or less and biopsy Gleason score 7 or less only sentinel nodes were removed. In men with prostate specific antigen more than 20 ng/ml or Gleason score greater than 7 extended pelvic lymph node dissection was also performed. RESULTS: Positive lymph nodes were found in 207 men (19.6%). In 63.3% of the men these lymph nodes were detected outside of the region of standard lymphadenectomy. The percent of patients with positive nodes was greater than predicted by currently used nomograms. The higher the preoperative prostate specific antigen, pathological stage and grade, the greater the percent of men with positive sentinel and nonsentinel lymph nodes (p<0.001). CONCLUSIONS: When deciding on pelvic lymph node dissection, sentinel or extended lymphadenectomy should be performed since more than half of patients have positive nodes outside of the region of standard lymphadenectomy. In cases of positive sentinel nodes extended lymph node dissection should be performed since tumor cells are also detectable in nonsentinel lymph nodes.