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Biomedical subjects

Albert Chen

Publications and source records attributed to Albert Chen.

11 recordsLinked to original sources

Differences in binding specificity for the homologous gamma- and beta-chain "holes" on fibrinogen: exclusive binding of Ala-His-Arg-Pro-amide by the beta-chain hole.

The beta-chain amino-terminal sequences of all known mammalian fibrins begin with the sequence Gly-His-Arg-Pro- (GHRP-), but the homologous sequence in chicken fibrin begins with the sequence Ala-His-Arg-Pro- (AHRP-). Nonetheless, chicken fibrinogen binds the synthetic peptide GHRPam, and a previously reported crystal structure has revealed that the binding is in exact conformance with that observed for the human GHRPam-fragment D complex. We now report that human fibrinogen, which is known not to bind APRP, binds the synthetic peptide AHRPam. Moreover, a crystal structure of AHRPam complexed with fragment D from human fibrinogen shows that AHRPam binds exclusively to the beta-chain hole and, unlike GHRPam, not at all to the homologous gamma-chain hole. The difference can be attributed to the methyl group of the alanine residue clashing with a critical carboxyl group in the gammaC hole but being accommodated in the roomier betaC hole where the equivalent carboxyl is situated more flexibly.

Animals↗

TE-averaged two-dimensional proton spectroscopic imaging of glutamate at 3 T.

Glutamate and glutamine are important neurochemicals in the central nervous system and the neurotoxic properties of excess glutamate have been associated with several neurodegenerative diseases. The TE-Averaged PRESS technique has been shown by our group to detect an unobstructed glutamate signal at 3 T that is resolved from glutamine and NAA at 2.35 ppm. TE-Averaged PRESS therefore provides an unambiguous measurement of glutamate as well as other metabolites such as NAA, choline, creatine, and myo-inositol. In this study, we extend the single voxel TE-Averaged PRESS technique for two-dimensional (2D) spectroscopic imaging (TE-Averaged MRSI) to generate 2D glutamate maps. To facilitate TE-Averaged MRSI within a reasonable time, a fast encoding trajectory was used. This enabled rapid acquisition of TE-Averaged spectral arrays with good spectral bandwidth (977 Hz) and resolution (approximately 2 Hz). MRSI data arrays of 10 x 16 were acquired with 1.8 cm3 spatial resolution over a approximately 110 cm3 volume in a scan time of approximately 21 min. Two-dimensional metabolite maps were obtained with good SNR and clear differentiation in glutamate levels was observed between gray and white matter with significantly higher glutamate in gray matter relative to white matter as anticipated.

Aspartic Acid↗

Radiological evaluation of bone growth in neonates born at gestational ages between 26 and 41 weeks: cross-sectional study.

The length of the ossified part of the long bones of the upper (humerus) and lower limb (femur) as well as the axial length (that is, height) of the vertebral body of L1 were measured on a plain supine radiograph in 347 newborn babies (228 males, 119 females) with the gestational age (GA) from 26 to 41 weeks. All were admitted to the neonatal intensive care unit. Reasons for admission included hyaline membrane disease, meconium aspiration syndrome, neonatal asphyxia or transient tachypnea of the newborn. Patients with abnormal growth, gross anomalies, or who were the products of multiple births were excluded. The average weekly increment in the height of L1 for male infants born at GA varying from 26 to 41 weeks was 0.23 mm, for the humerus 1.82 mm and for the femur 2.35 mm. The corresponding data for females was 0.20 mm, 1.54 mm and 2.30 mm. The ratio of the height of L1 to body length progressively increased between 26 to 41 weeks. A growth spurt in L1 was noted for both sexes at 34 weeks of GA. Long bone growth was similar in male and female infants born before 36 weeks. However, the ratio of femur to body length in males increased after 36 weeks. The ratio of humerus to body length remained constant over the entire range of GA.

Bone Development↗

Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule.

The Abeta1-42 peptide that is overproduced in Alzheimer's disease (AD) from a large precursor protein has a normal amino acid sequence but, when liberated, misfolds at neutral pH to form "protofibrils" and fibrils that are rich in beta-sheets. We find that these protofibrils or fibrils are toxic to certain neuronal cells that carry Ca-permeant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Disrupting the structure of the Abeta1-42 fibrils and protofibrils might lead to the discovery of molecules that would be very useful in the treatment of AD. A high-throughput screen of a library of >3,000 small molecules with known "biological activity" was set up to find compounds that efficiently decrease the beta-sheet content of aggregating Abeta1-42. Lead compounds were characterized by using thioflavin T (ThT) as a beta-sheet assay. The most effective of six compounds found was 4,5-dianilinophthalimide (DAPH) under the following conditions: DAPH at low micromolar concentrations abolishes or greatly reduces previously existing fully formed Abeta1-42 fibrils, producing instead amorphous materials without fibrils but apparently containing some protofibrils and smaller forms. Coincubation of the Abeta1-42 peptide with DAPH produces either amorphous materials or empty fields. Coincubation of DAPH and Abeta1-42 greatly reduces the beta-sheet content, as measured with ThT fluorescence, and produces a novel fluorescent complex with ThT. When the Abeta1-42 peptide was coincubated with DAPH at very low micromolar concentrations, the neuronal toxicity mentioned above (Ca(2+) influx) was eliminated. Clearly, DAPH is a promising candidate for AD therapy.

Alzheimer Disease↗

Static and dynamic compression modulate matrix metabolism in tissue engineered cartilage.

Static and dynamic compression are known to modulate the metabolism of articular cartilage. The present study focused on determining the effects of compressive loading on the metabolism of sulfated glycosaminoglycans (S-GAG) and protein in tissue engineered cartilage constructs. Cartilage constructs were subjected to static or dynamic compression for 24 h and radiolabeled with 35SO4 and 3H-proline to assess the total synthesis and percentage retention of S-GAG and total protein, respectively. Static compression at an amplitude of 50% suppressed the synthesis of both S-GAG and protein by 35% and 57%, respectively. Dynamic compression at an amplitude of 5% had stimulatory effects on synthesis that were dependent on the static offset compression amplitude (10% or 50%) and dynamic compression frequency (0.001 or 0.1 Hz). Thus, tissue engineered cartilage demonstrated the ability to respond to mechanical loading in a manner similar to that observed with articular cartilage. Mechanical loading may therefore potentially be used to modulate the growth of cartilaginous tissues in vitrd, potentially facilitating the culture of functional cartilage tissues suitable for implantation.

Animals↗

Nasal teeth: report of three cases.

The ectopic eruption of the teeth into the nasal cavity is a rare phenomenon. We report cases: two involving the nasal cavity and one involving the hard palate and complicated by Aspergillus rhinitis. We describe the clinical and radiologic presentation of these cases and discuss their etiology, complications, diagnosis, and treatment.

Aspergillosis↗

Primary synovial osteochondromatosis of the first metatarsophalangeal joint.

Synovial osteochondromatosis is an uncommon disorder, generally seen in large joints such as the knee, elbow, shoulder, hip and ankle. We report a 35-year-old man with synovial osteochondromatosis of the metatarsophalangeal joint of the great toe. Despite the rarity of the location, the radiographic appearance ought to suggest the diagnosis. Histological confirmation is required, since malignancy cannot be totally ruled out clinically and radiographically.

Adult↗

Distinguishing multiple rice body formation in chronic subacromial-subdeltoid bursitis from synovial chondromatosis.

Multiple rice body formation is a complication of chronic bursitis. Although it resembles synovial chondromatosis clinically and on imaging, the literature suggests that analysis of radiographic and MR appearances should allow discrimination. We report the imaging findings in a 41-year-old man presenting with rice body formation in chronic subacromial-subdeltoid bursitis. We found that the signal intensity of the rice bodies is helpful in making the diagnosis.

Bursitis↗