Three-dimensional structure of the yeast ribosome

The 80S ribosome from Saccharomyces cerevisiae has been reconstructed from cryo electron micrographs to a resolution of 35 A. It is strikingly similar to the 70S ribosome from Escherichia coli, while displaying the characteristic eukaryotic features familiar from reconstructions of ribosomes from higher eukaryotes. Aside from the elaboration of a number of peripherally located features on the two subunits and greater overall size, the largest difference between the yeast and E.coli ribosomes is in a mass increase on one side of the large (60S) subunit. It thus appears more elliptical than the characteristically globular 50S subunit from E.coli. The interior of the 60S subunit reveals a variable diameter tunnel spanning the subunit between the interface canyon and a site on the lower back of the subunit, presumably the exit site through which the nascent polypeptide chain emerges from the ribosome.     

Sonographic incidence of deep venous thrombosis contralateral to hip or knee replacement surgery

PURPOSE: This study assesses the sonographic incidence of deep venous thrombosis (DVT) contralateral to and the venographic incidence ipsilateral to hip or knee replacement surgery and the role of sonography in routine surveillance. METHODS: We prospectively evaluated 178 consecutive patients with sonography of the femoropopliteal venous systems of the contralateral lower extremity and venography of the ipsilateral lower extremity on days 3 and 4, respectively, after total hip or knee replacement surgery. RESULTS: No cases of acute DVT and only 1 case of chronic DVT isolated to the popliteal system were identified by sonography in the contralateral extremity. In the ipsilateral extremity, venography identified 26 patients with acute DVT (3 femoropopliteal, 21 calf, and 2 concurrent femoropopliteal and calf). CONCLUSIONS: Routine sonographic evaluation of the lower extremity contralateral to hip or knee replacement surgery is not cost-effective because of the extremely low incidence of detectable acute thrombus.     

Abnormal microenvironmental signals underlie intestinal aganglionosis in Dominant megacolon mutant mice

Dominant megacolon (Dom) is a mutation in an uncharacterized murine gene which is associated with intestinal aganglionosis and the focal absence of melanocytes in heterozygous animals. The phenotype of Dom/+ heterozygotes is similar to the lethal spotted and piebald lethal mutations, which are due to defects in endothelin-mediated intercellular signals. In this study, the DbetaH-nlacZ transgenic marker for enteric neural crest cells is used to study the distribution of enteric neurons and their precursors in Dom/+ mice and embryos. Vagal neural crest-derived cells in wild-type embryos colonize the gut in a cranial-to-caudal progression. In Dom/+ embryos, colonization was retarded from the earliest stages examined (embryonic Day 11.0), including progression through the small intestine. The early onset of this defect contrasts with impaired neural crest colonization associated with the lethal spotted and piebald lethal mutations which manifest only in the large intestine. Analysis of Dom/+ - +/+ aggregation chimeras indicated that defective colonization is not an autonomous (intrinsic) property of Dom/+ neuroblasts, but like lethal spotted and piebald lethal, the Dominant megacolon mutation directly or indirectly affects microenvironmental signals which influence the migration, proliferation, and/or survival of enteric neural crest cells.     

Optimization of PET activation studies based on the SNR measured in the 3-D Hoffman brain phantom

When a linear magnetic field gradient is used, spatially higher-order magnetic fields are produced to satisfy the Maxwell equations. It has been observed that the higher-order magnetic field produced by the readout gradient causes axial echo planar images acquired with a horizontal solenoid magnet to shift along the phase-encoding direction and lose image intensities. Both the shift and intensity reduction become increasingly severe as the slice offset from the isocenter increases. These phenomena are quantitatively analyzed, and good correlation between experiments and theory has been established. The analysis also predicts a previously unreported Nyquist ghost on images with very large slice offsets. This ghost has been verified with computer simulations. Based on the analysis, several methods have been developed to eliminate the image shift, the intensity reduction, and the ghost. Selected methods have been implemented on a commercial scanner and proved effective in removing these image artifacts.     

Value of anterior chamber lenses in developing countries. Results of a clinical study

There are estimated to be 20 million people blinded by cataracts, 80-90% of whom live in rural areas of developing countries where expert surgical resources are scarce. The majority of all cataract operations are still intracapsular extractions (ICCE). Aphakic correction using spectacles is problematical in developing countries. This study was undertaken to evaluate the safety of multiflex open loop anterior chamber intraocular lenses (AC IOLs). METHODS: A total of 2000 people attending Lahan Eye Hospital, South-east Nepal, with bilateral cataract were randomly allocated to receive in their first eye either ICCE with AC IOL (AC IOL group) or ICCE with aphakic correction (control group). All operations were performed by two ophthalmologists using a standardized technology and 4.5 x operating loupe magnification. Functional and best corrected vision was recorded. The primary outcome measure was poor vision after surgery, which was defined as a visual acuity of less than 6/60 at 1 year follow-up (WHO definition for severe visual impairment and blindness). FINDINGS: The median time needed to perform ICCE was 4.1 min and to perform ICCE with AC IOL 6 min. Of all study patients 91% were examined after 1 year. Five percent of the AC IOL group and 5.4% of the control group had a functional visual acuity of less than 6/60. Causes of reduced vision in the AC IOL group versus the control group were: correctable refractive error (22 vs 29), uveitis/secondary glaucoma (13 vs 2), endophthalmitis (4 vs 7), pre-existing eye diseases (4 vs 5), retinal detachment (0 vs 4), and corneal decompensation (0 vs 1). Of the control group, 24 patients were found to be functionally blind in the operated eye (vision < 3/60) because they did not wear their aphakic spectacles. Normal vision (WHO definition: > or = 6/18) was achieved best corrected in 89.9% of the AC IOL group and 93.2% of the control group. Analysis of additional long-term follow-ups (2-5 years post-operatively) has not yet been completed. INTERPRETATION: This study provides evidence that in developing countries well-manufactured multiflex open loop AC IOLs can be implanted safely by experienced ophthalmologists after routine ICCE, avoiding the disadvantages of aphakic spectacle correction.     

Hyperglycemic levels of glucose inhibit interleukin 1 release from RAW 264.7 murine macrophages by activation of protein kinase C

Diabetic patients with hyperglycemia (high blood glucose) have frequent and persistent bacterial infections linked to significantly diminished bactericidal activity and macrophage function. Interleukin-1 (IL-1), released primarily from activated macrophages, is a key mediator of effective host defense against microorganisms. We observe that hyperglycemic levels of D-glucose (8-20 mM) inhibit the release of IL-1 by lipopolysaccharide-stimulated RAW 264.7 murine macrophage cells. An inhibitor of glucose transport and metabolism, 2-deoxyglucose, prevents this inhibition of IL-1 release. High levels (8-20 mM) of fructose and mannose (but not galactose or L-glucose) also inhibit the release of IL-1 activity, suggesting that metabolism is required for IL-1 inhibition. Immunoprecipitation and activity measurements demonstrate that high glucose levels block the release of IL-1 but do not inhibit IL-1 production. High glucose levels (20 mM) increase protein kinase C (PKC) activity, and inhibitors of PKC block the inhibitory effects of glucose. Phorbol 12-myristate 13-acetate, an agonist of PKC, mimics glucose-induced inhibition of IL-1 release. These results demonstrate that high glucose levels inhibit IL-1 release (but not production) by RAW 264. 7 murine macrophages, and this inhibition is mediated by PKC activation. These studies suggest that persistent infections in hyperglycemic patients may be due to an inhibition of IL-1 release from macrophages.     

How standard is a standard day during a standard ambulatory 24-hour esophageal pH monitoring?

BACKGROUND: Ambulatory 24-h esophageal pH monitoring is the gold standard method for measuring esophageal exposure to gastric acid. The method has gained acceptability because of its sensitivity, specificity, and accuracy and also because it is easy to perform, well tolerated, and quite physiologic. However, whether ambulatory esophageal pH-metry affects normal lifestyle has not been specifically evaluated. METHODS: We investigated 114 consecutive patients admitted to our Unit because of heartburn, acid regurgitation, or non-cardiac chest pain. Patients filled in a diary chart on 2 different days: 1 day while the pH-metry was performed and another normal day, to record the following variables: number, amount, and composition of the meals; time in supine position; number of cigarettes smoked; alcohol intake; degree of physical activity; and number and type of symptomatic episodes. Patients were encouraged to carry out normal activity. RESULTS: When the 2 days were compared, none of the registered variables appeared to differ, with the exception of subjective evaluation of physical activity: 65% of the patients said their physical activity was diminished during the test day relative to their usual standard. CONCLUSIONS: Normal habits are not significantly modified by 24-h esophageal pH-metry, with the exception of physical activity, which decreases, possibly owing more to aesthetic than to physical problems.     

VIP10高速运算放大器的PSPICE数据库

从零开始创建运算放大器的SPICE电路仿真模型不仅困难而且很费时间。美国国家半导体公司建立了OrCAD Capture数据库(nationalhighspeed.olb)以及PSPICE电路模型数据库(nationalhighspeed.lib),用以存储业内领先的 VIP10工艺的高速运算放大器资料,其中包括 LMH 系列高速运算放大器的性能模型及运算放大器的电路原理图符号。登录amplifiers.national.com网页便可下载这两个数据库的资料。VIP10 工艺技术是一种高速的电介质绝缘的互补双极集成电路技术,可以将深沟技术应用到压焊晶片上实现完全的电介质绝缘,以及最佳的高速放大器性能…