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A Cheng

Publications and source records attributed to A Cheng.

At least 91 records · Page 5Linked to original sources
PubMed1997

NEAR's flyby of 253 mathilde: images of a C asteroid

On 27 June 1997, the Near Earth Asteroid Rendezvous (NEAR) spacecraft flew within 1212 kilometers of asteroid 253 Mathilde. Mathilde is an irregular, heavily cratered body measuring 66 kilometers by 48 kilometers by 46 kilometers. The asteroid's surface is dark (estimated albedo between 0.035 and 0.050) and similar in color to some CM carbonaceous chondrites. No albedo or color variations were detected. The volume derived from the images and the mass from Doppler tracking of the spacecraft yield a mean density of 1.3 +/- 0.2 grams per cubic centimeter, about half that of CM chondrites, indicating a porous interior structure.

Journal Article↗
PubMed1997

Fostriecin, an antitumor antibiotic with inhibitory activity against serine/threonine protein phosphatases types 1 (PP1) and 2A (PP2A), is highly selective for PP2A.

Fostriecin, an antitumor antibiotic produced by Streptomyces pulveraceus, is a strong inhibitor of type 2A (PP2A; IC50 3.2 nM) and a weak inhibitor of type 1 (PP1; IC50 131 microM) serine/threonine protein phosphatases. Fostriecin has no apparent effect on the activity of PP2B, and dose-inhibition studies conducted with whole cell homogenates indicate that fostriecin also inhibits the native forms of PP1 and PP2A. Studies with recombinant PP1/PP2A chimeras indicate that okadaic acid and fostriecin have different binding sites.

Alkenes↗
PubMed1997

Genomic organization of the human PP4 gene encoding a serine/threonine protein phosphatase (PP4) suggests a common ancestry with PP2A.

Serine/threonine protein phosphatase type 4 (PP4) belongs to a family of okadaic acid and microcystin-LR-sensitive protein phosphatases. In this study, we report the cloning and characterization of the human PP4 gene. The gene spans about 10 kb and includes one untranslated and eight translated exons. The 5' flanking region of the gene is rich in G and C (60.1%) and lacks TATA and CAAT boxes. Sequence analysis of the 5'-flanking region reveals potential binding sites for transcription factors SP1, AP1, AP2, and several gamma-IRE-CS sites. Two transcription initiation sites were mapped by ribonuclease protection analysis, one to 54 and the other to 84 bp upstream of the ATG initiation codon. PCR analysis of a human/rodent somatic cell hybrid panel maps PP4 to chromosome 16, and comparison of the PP4 gene structure with that of PP2A and PP1 suggests that PP4 is more closely related to PP2A than PP1.

Amino Acid Sequence↗
PubMed1997

The amino terminus of JAK3 is necessary and sufficient for binding to the common gamma chain and confers the ability to transmit interleukin 2-mediated signals.

JAK3 is a protein tyrosine kinase that specifically associates with the common gamma chain (gammac), a shared subunit of receptors for interleukin (IL) 2, 4, 7, 9, and 15. Patients deficient in either JAK3 or gammac presented with virtually identical forms of severe combined immunodeficiency (SCID), underscoring the importance of the JAK3-gammac interaction. Despite the key roles of JAK3 and gammac in lymphocytic development and function, the molecular basis of this interaction remains poorly understood. In this study, we have characterized the regions of JAK3 involved in gammac association. By developing a number of chimeric JAK3-JAK2 constructs, we show that the binding specificity to gammac can be conferred to JAK2 by transferring the N-terminal domains of JAK3. Moreover, those JAK3-JAK2 chimeras capable of binding gammac were also capable of reconstituting IL-2 signaling as measured by inducible phosphorylation of the chimeric JAK3-JAK2 protein, JAK1, the IL-2 receptor beta chain, and signal transducer and activator of transcription 5A. Subsequent deletion analyses of JAK3 have identified the N-terminal JH7-6 domains as a minimal region sufficient for gammac association. Furthermore, expression of the mutant containing only the JH7-6 domains effectively competed with full-length JAK3 for binding to gammac. We conclude that the JH7-6 domains of JAK3 are necessary and sufficient for gammac association. These studies offer clues toward a broader understanding of JAK-mediated cytokine signaling and may provide a target for the development of novel therapeutic modalities in immunologically mediated diseases.

3T3 Cells↗
PubMed1997

Three-dimensional organization of a human water channel.

Aquaporins (AQP) are members of the major intrinsic protein (MIP) superfamily of integral membrane proteins and facilitate water transport in various eukaryotes and prokaryotes. The archetypal aquaporin AQP1 is a partly glycosylated water-selective channel that is widely expressed in the plasma membranes of several water-permeable epithelial and endothelial cells. Here we report the three-dimensional structure of deglycosylated, human erythrocyte AQP1, determined at 7 A resolution in the membrane plane by electron crystallography of frozen-hydrated two-dimensional crystals. The structure has an inplane, intramolecular 2-fold axis of symmetry located in the hydrophobic core of the bilayer. The AQP1 monomer is composed of six membrane-spanning, tilted alpha-helices. These helices form a barrel that encloses a vestibular region leading to the water-selective channel, which is outlined by densities attributed to the functionally important NPA boxes and their bridges to the surrounding helices. The intramolecular symmetry within the AQP1 molecule represents a new motif for the topology and design of membrane protein channels, and is a simple and elegant solution to the problem of bidirectional transport across the bilayer.

Aquaporin 1↗
PubMed1997

Ice-binding mechanism of winter flounder antifreeze proteins.

We have studied the winter flounder antifreeze protein (AFP) and two of its mutants using molecular dynamics simulation techniques. The simulations were performed under four conditions: in the gas phase, solvated by water, adsorbed on the ice (2021) crystal plane in the gas phase and in aqueous solution. This study provided details of the ice-binding pattern of the winter flounder AFP. Simulation results indicated that the Asp, Asn, and Thr residues in the AFP are important in ice binding and that Asn and Thr as a group bind cooperatively to the ice surface. These ice-binding residues can be collected into four distinct ice-binding regions: Asp-1/Thr-2/Asp-5, Thr-13/Asn-16, Thr-24/Asn-27, and Thr-35/Arg-37. These four regions are 11 residues apart and the repeat distance between them matches the ice lattice constant along the (1102) direction. This match is crucial to ensure that all four groups can interact with the ice surface simultaneously, thereby, enhancing ice binding. These Asx (x = p or n)/Thr regions each form 5-6 hydrogen bonds with the ice surface: Asn forms about three hydrogen bonds with ice molecules located in the step region while Thr forms one to two hydrogen bonds with the ice molecules in the ridge of the (2021) crystal plane. Both the distance between Thr and Asn and the ordering of the two residues are crucial for effective ice binding. The proper sequence is necessary to generate a binding surface that is compatible with the ice surface topology, thus providing a perfect "host/guest" interaction that simultaneously satisfies both hydrogen bonding and van der Waals interactions. The results also show the relation among binding energy, the number of hydrogen bonds, and the activity. The activity is correlated to the binding energy, and in the case of the mutants we have studied the number of hydrogen bonds. The greater the number of the hydrogen bonds the greater the antifreeze activity. The roles van der Waals interactions and the hydrophobic effect play in ice binding are also highlighted. For the latter it is demonstrated that the surface of ice has a clathratelike structure which favors the partitioning of hydrophobic groups to the surface of ice. It is suggested that mutations that involve the deletion of hydrophobic residues (e.g., the Leu residues) will provide insight into the role the hydrophobic effect plays in partitioning these peptides to the surface of ice.

Amino Acid Sequence↗
PubMed1997

Warfarin skin necrosis in a postpartum woman with protein S deficiency.

BACKGROUND: Warfarin-induced skin necrosis is a rare and dangerous complication affecting 0.01-0.1% of patients on warfarin. Deficiencies in protein C or protein S in association with other factors have been implicated in its etiology. No report has described this disorder in the immediate postpartum period in patients with protein S deficiency. CASE: A 1-week postpartum woman with known protein S deficiency presented with skin necrosis after a previously uneventful course of warfarin. CONCLUSION: Reduced levels of free protein S during the antepartum and immediate postpartum periods predispose protein S-deficient women to warfarin skin necrosis. Previously uncomplicated courses of warfarin do not obviate the possibility of skin necrosis with future warfarin administrations. Initiation of low-dose warfarin with heparin can reduce the likelihood of this disorder.

Adult↗
PubMed1997

Recovery of extra plasma during preparation of platelet concentrates using a new centrifugation support.

During blood component preparation of standard blood donations a major loss of plasma occurs whenever platelet concentrates (PC) are produced, especially when the platelets are prepared by the platelet-rich plasma (PRP) method. This loss is partly due to the use of plasma for resuspension of the platelet pellet but the main loss is associated with the slow first spin used to prepare PRP. This slow first spin results in an undesirably low haematocrit and a red-cell concentrate which contains a large volume of trapped plasma which is lost to the fractionation plant. We have developed a method of recovering most of this plasma from the soft-spun red cells by including the red-cell concentrate (RCC) in the second spin during preparation of the platelet pellet. To allow recovery of the second spin plasma from the half-full RCC bag we have developed a simple bag support, the Perth BagRap. Development of the method proved difficult due to the high g forces but the final technique evolved was simple and inexpensive. The method was easily introduced into routine use and resulted in a 53% increase in plasma per three-product unit.

Blood Donors↗
PubMed1997

Evidence for DNA-PK-dependent and -independent DNA double-strand break repair pathways in mammalian cells as a function of the cell cycle.

Mice homozygous for the scid (severe combined immune deficiency) mutation are defective in the repair of DNA double-strand breaks (DSBs) and are consequently very X-ray sensitive and defective in the lymphoid V(D)J recombination process. Recently, a strong candidate for the scid gene has been identified as the catalytic subunit of the DNA-dependent protein kinase (DNA-PK) complex. Here, we show that the activity of the DNA-PK complex is regulated in a cell cycle-dependent manner, with peaks of activity found at the G1/early S phase and again at the G2 phase in wild-type cells. Interestingly, only the deficit of the G1/early S phase DNA-PK activity correlated with an increased hypersensitivity to X-irradiation and a DNA DSB repair deficit in synchronized scid pre-B cells. Finally, we demonstrate that the DNA-PK activity found at the G2 phase may be required for exit from a DNA damage-induced G2 checkpoint arrest. These observations suggest the presence of two pathways (DNA-PK-dependent and -independent) of illegitimate mammalian DNA DSB repair and two distinct roles (DNA DSB repair and G2 checkpoint traversal) for DNA-PK in the cellular response to ionizing radiation.

Animals↗
PubMed1997

Correlation between retinal fluorescein angiography and blood viscosity and other factors in patients with primary open angle glaucoma.

OBJECTIVE: To investigate the correlation among retinal fluorescein angiography, blood viscosity, and other factors in patients with open angle glaucoma (POAG). METHODS: Multiple step regression analysis was made to investigate the correlation between each of the following blood vessel filling times: the arm-choroid (A-CT), arm-retinal artery (A-AT), and retinal artery-venous (A-VT) of the fundus fluorescein angiography (FFA) in 122 eyes with POAG and each of the following related factors in hemorrheology: whole blood apparent viscosity at low, medium and high shear rates, plasma viscosity and hematocrit. Also, the same analysis was applied to investigate the correlation between each of the A-AT, A-VT of the FFA in 70 eyes with POAG and the following factors: systolic blood pressure, diastolic blood pressure, age and whole blood apparent viscosity at low shear rate. RESULTS: The whole blood apparent viscosity at low shear rate was closely related to A-CT and A-AT, while hematocrit was closely related to A-VT of the FFA. The whole blood apparent viscosity at low shear rate and age, especially the whole blood apparent viscosity, was closely related to A-AT, A-VT of the FFA. CONCLUSION: Blood viscosity can affect the filling times of the FFA in POAG.

Blood Viscosity↗
PubMed1997

[A preliminary report on clinical application of biopoly ester ligament].

Sixty-one cases of fracture or dislocation were treated with France-made biopolyester ligament. They consisted of 18 cases of fracture of patella, 13 cases of fracture of olecranon, 8 cases of fracture of distal clavicle, 10 cases of dislocation of acromino-clavicular joint, 6 cases of separation of lower tibio-fibular joint, 3 cases of rapture of cruciate ligament and 3 cases of fracture of upper third of ulna with dislolcation of radial head. The follow-up period lasted from 3 to 12 months with an average of 7.3 months. The result showed that of the 56 follow-up cases, 49 were excellent and 7 were satisfactory. There was no redisplacement occured in this group. The Biopolyester ligament was believed to be a good and safe material for fractures or dislocations and was of good strength of extension and easy to use.

Adolescent↗
PubMed1996

Prospective clinical evaluation of an electronic portal imaging device.

PURPOSE: To determine whether the clinical implementation of an electronic portal imaging device can improve the precision of daily external beam radiotherapy. METHODS AND MATERIALS: In 1991, an electronic portal imaging device was installed on a dual energy linear accelerator in our clinic. After training the radiotherapy technologists in the acquisition and evaluation of portal images, we performed a randomized study to determine whether online observation, interruption, and intervention would result in more precise daily setup. The patients were randomized to one of two groups: those whose treatments were actively monitored by the radiotherapy technologists and those that were imaged but not monitored. The treating technologists were instructed to correct the following treatment errors: (a) field placement error (FPE) > 1 cm; (b) incorrect block; (c) incorrect collimator setting; (d) absent customized block. Time of treatment delivery was recorded by our patient tracking and billing computers and compared to a matched set of patients not participating in the study. After the patients radiation therapy course was completed, an offline analysis of the patient setup error was planned. RESULTS: Thirty-two patients were treated to 34 anatomical sites in this study. In 893 treatment sessions, 1,873 fields were treated (1,089 fields monitored and 794 fields unmonitored). Ninety percent of the treated fields had at least one image stored for offline analysis. Eighty-seven percent of these images were analyzed offline. Of the 1,011 fields imaged in the monitored arm, only 14 (1.4%) had an intervention recorded by the technologist. Despite infrequent online intervention, offline analysis demonstrated that the incidence of FPE > 10 mm in the monitored and unmonitored groups was 56 out of 881 (6.1%) and 95 out of 595 (11.2%), respectively; p < 0.01. A significant reduction in the incidence of FPE > 10 mm was confined to the pelvic fields. The time to treat patients in this study was 10.78 min (monitored) and 10.10 min (unmonitored). Features that were identified that prevented the technologists from recognizing more errors online include poor image quality inherent to the portal imaging device used in this study, artifacts on the portal images related to table supports, and small field size lacking sufficient anatomical detail to detect FPEs. Furthermore, tools to objectively evaluate a portal image for the presence of field placement error were lacking. These include magnification factor corrections between the simulation of portal image, online measurement tools, image enhancement tools, and image registration algorithms. CONCLUSION: The use of an electronic portal imaging device in our clinic has been implemented without a significant increase in patient treatment time. Online intervention and correction of patient positioning occurred rarely, despite FPEs of > 10 mm being present in more than 10% of the treated fields. A significant reduction in FPEs exceeding 10 mm was made in the group of patients receiving pelvic radiotherapy. It is likely that this improvement was made secondarily to a decrease in systematic error and not because of online interventions. More significant improvements in portal image quality and the availability of online image registration tools are required before substantial improvements can be made in patient positioning with online portal imaging.

Brain Neoplasms↗
PubMed1996

Free radical mediated x-ray damage of model membranes.

The damaging effects of synchrotron-derived x rays on aqueous phospholipid dispersions have been evaluated. The effect of degree of lipid hydration, phospholipid chemical structure, mesophase identity, aqueous medium composition, and incident flux on the severity and progress of damage was quantified using time-resolved x-ray diffraction and chromatographic analysis of damage products. Electron spin resonance measurements of spin-trapped intermediates generated during irradiation suggest a free radical-mediated process. Surprisingly, radiation damage effects revealed by x-ray diffraction were imperceptible when the lamellar phases were prepared under water-stressed conditions, despite the fact that x-ray-induced chemical breakdown of the lipid occurred regardless of hydration level. Of the fully hydrated lipid systems studied, saturated diacyl-phosphatidylcholines were most sensitive to radiation damage compared to the ester- and ether-linked phosphatidylethanolamines and the ether-linked phosphatidylcholines. The inclusion of buffers or inorganic salts in the dispersing medium had only a minor effect in reducing damage development. A small inverse dose-rate effect was found when the x-ray beam intensity was changed 15-fold. These results contribute to our understanding of the mechanism of radiation damage, to our appreciation of the importance of monitoring both structure and composition when evaluating biomaterials radiation sensitivity, and to the development of strategies for eliminating or reducing the severity of damage due to an increasingly important source of x rays, synchrotron radiation. Because damage is shown to be free radical mediated, these results have an important bearing on age-related accumulation of free radicals in cells and how these might compromise membrane integrity, culminating in cell death.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

The risks of hip fracture in older people from private homes and institutions.

This study aimed to determine whether the incidence of hip fracture is greater among those living in institutions compared with those living in private homes. Over two and a half years of surveillance, 1832 hip fractures were identified, of which 58% were sustained by those living in private homes and 42% by those living in institutions. The risks of hip fracture, unadjusted for age and sex, were 10.5 times greater for those living in institutions compared with those living in private homes. After adjusting for age and sex, these greatly increased risks were maintained, although for both men and women the risks decreased with age, such that at ages over 90 years the risks were not significantly different. Given these findings, hip fracture prevention strategies that focus particularly on individuals within institutions are highly commended.

Aged↗