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Biomedical subjects

B K Ho

Publications and source records attributed to B K Ho.

At least 19 recordsLinked to original sources
PubMed2001

Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis.

Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

Age of Onset↗
PubMed1998

Temporal variation in parasuicide among Singaporean Chinese.

OBJECTIVE: The aim of this study was to determine whether there is any temporal variation in the incidence of parasuicide within the Chinese community and, if possible, to correlate the findings with prevailing cultural and social influences. METHOD: All patients of Chinese origin referred to a teaching hospital in Singapore between 1990 and 1994 were included in the study. The cases were divided by sex and aggregated for the month and day of the week in which the parasuicides occurred. RESULTS: Cases of parasuicide peaked on Mondays, while the lowest incidences occurred on Saturdays. The peak months were June, August and September with a trough in December and January. CONCLUSIONS: The findings may not be amenable to any single explanation but the peak months coincided with the month of the Hungry Ghosts, which is believed to be a particularly inauspicious period, while the trough occurred during a festive period. Similarly, looking at the student population, the peaks coincided with the examination period. It appears that social and cultural factors play a significant role in the temporal variation in parasuicide in Singapore.

Adolescent↗
PubMed1997

The differential in vitro stimulation of 3',5'-cyclic nucleotide phosphodiesterase by calcium binding proteins.

A heterogeneous class of proteins exhibit within their sequence a particular structure, named EF-hand, able to bind calcium with high affinity. These calcium binding proteins have been described in most cells and tissues and are suggested to work as calcium buffers, thereby participating in the regulation of calcium-dependent cellular activity. Recent circumstantial evidences suggest that calcium binding proteins may serve other functions as well, possibly as enzyme modulators. Since 3',5'-cyclic nucleotide phosphodiesterase is a well-known calmodulin-modulated enzyme, in this work we studied the effect in vitro of different purified calcium binding proteins on the activity of this enzyme. Among the proteins tested, calmodulin and recombinant rat brain parvalbumin could stimulate the 3',5'-cyclic nucleotide phosphodiesterase activity in vitro, whereas rabbit muscle parvalbumin, rat renal and brain calbindin D28K, and bovine brain S-100B were ineffective. Immunoprecipitation with the specific antiserum completely abolished either calmodulin or recombinant brain parvalbumin activation of 3',5'-cyclic nucleotide phosphodiesterase. Moreover, while the presence of calcium in the incubation mixture was critical in the calmodulin-mediated stimulation of the enzyme, it did not modify the effect of the recombinant brain parvalbumin. We suggest that, in addition to calmodulin, parvalbumin may be a regulator of 3',5'-cyclic nucleotide phosphodiesterase, and possibly of other yet to be identified enzymes in certain tissues.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Expression of calbindin-D28K in motoneuron hybrid cells after retroviral infection with calbindin-D28K cDNA prevents amyotrophic lateral sclerosis IgG-mediated cytotoxicity.

Calbindin-D28K and/or parvalbumin appear to influence the selective vulnerability of motoneurons in amyotrophic lateral sclerosis (ALS). Their immunoreactivity is undetectable in motoneurons readily damaged in human ALS, and in differentiated motoneuron hybrid cells [ventral spinal cord (VSC 4.1 cells)] that undergo calcium-dependent apoptotic cell death in the presence of ALS immunoglobulins. To provide additional evidence for the role of calcium-binding proteins in motoneuron vulnerability, VSC 4.1 cells were infected with a retrovirus carrying calbindin-D28K cDNA under the control of the promoter of the phosphoglycerate kinase gene. Differentiated calbindin-D28K cDNA-infected cells expressed high calbindin-D28K and demonstrated increased resistance to ALS IgG-mediated toxicity. Treatment with calbindin-D28K antisense oligodeoxynucleotides, which significantly decreased calbindin-D28K expression, rendered these cells vulnerable again to ALS IgG toxicity.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Effect of conversion from a fee-for-service plan to a capitation reimbursement system on a circumscribed outpatient radiology practice of 20,000 persons.

PURPOSE: To assess the effect of a capitation reimbursement plan with attendant changes in service arrangements on the utilization of radiologic services, financially on the payer, and on the satisfaction of patients and referring physicians. MATERIALS AND METHODS: Outpatient radiologic services for a defined population of 20,000 company employees and their dependents were converted from a point-of-service managed care plan to a capitation payment plan. Under the capitation plan, nonemergent outpatient diagnostic imaging was performed at a newly constructed imaging center staffed by general radiologists. All cross-sectional images and certain projectional studies were also over-read (read again after the initial reading by local radiologists) by subspecialists. Utilization data obtained before and after the conversion were analyzed. The financial effect on the employer and the satisfaction of patients and physicians were also assessed. RESULTS: Quality imaging services were provided under the capitation plan with financial savings by the employer. Use was higher for cross-sectional imaging, especially magnetic resonance imaging studies, and was lower for nonmammographic plain radiography. Consumer satisfaction was high. CONCLUSION: Under certain conditions, conversion to a capitation system for imaging can lead to improved quality of care and decreased overall health-care costs.

Ambulatory Care↗
PubMed1996

Calbindin D28K forms a Ca(2+)-dissociable complex with mellitin in vitro.

Calbindin D28K (CB), a cytosolic calcium binding protein (CBP), forms a macromolecular complex with the polypeptide mellitin (ME) the absence of calcium, which can be reversibly dissociated by the addition of Ca2+. The molar ratio of CB:ME constituted in this complex is 1:4, suggesting that CB interacts with the tetrameric form of ME. Like free tetrameric ME, the CB:ME complex does not migrate into 15% non-denaturing polyacrylamide electrophoretic gels, although both constituents migrate normally after irreversible complex denaturation by heating in sodium dodecyl sulphate (SDS). The interaction of these two proteins can be distinguished from the association of calmodulin (CM) with ME, which forms a reversibly dissociable, equimolar complex in the presence of Ca2+ and a stable non-migrating complex (molar ratio = 1:12) in its absence. Thus, CB and CM appear to bind ME under different Ca2+ regulatory control, suggesting possible roles for CB as a Ca(2+)-dependent regulatory binding protein.

Animals↗
PubMed1995

beta-Amyloid1-40 increases expression of beta-amyloid precursor protein in neuronal hybrid cells.

Studies of cell injury and death in Alzheimer's disease have suggested a prominent role for beta-amyloid peptide (beta-AP), a 40-43-amino-acid peptide derived from a larger membrane glycoprotein, beta-amyloid precursor protein (beta-APP). Previous experiments have demonstrated that beta-AP induces cytotoxicity in a neuronal hybrid cell line (MES 23.5) in vitro. Here, we demonstrate that beta-APP mRNA content is increased 3.5-fold in 24 h after treatment with beta-AP1-40. Accompanying beta-AP1-40-induced cell injury, levels of cell-associated beta-APP and a C-terminal intermediate fragment are increased up to 15-fold, and levels of secreted forms of beta-APP and 12- and 4-kDa fragments are also increased. Application of beta-APP antisense oligodeoxynucleotide reduces both cytotoxicity and beta-APP expression. 6-Hydroxydopamine application or glucose deprivation causes extensive cell damage, but they do not increase beta-APP expression. These results suggest a selective positive feedback mechanism whereby beta-AP may induce cytotoxicity and increase levels of potentially neurotrophic as well as amyloidogenic fragments of beta-APP with the net consequence of further neuronal damage.

Amyloid beta-Peptides↗
PubMed1995

Technical considerations in planning a distributed teleradiology system.

A large-scale teleradiology project is under way to link a Florida imaging center to the UCLA Department of Radiology. The initial goal is to provide Florida patients in a routine clinical practice environment with subspecialty consultation by academic radiologists. The plan then calls for the addition of other domestic and international sites. Technical issues in planning to establish the necessary teleradiology infrastructure include wide area network design, image compression, distributed archiving, and special viewing station features. Special emphasis is placed on archive design that makes intelligent use of information, such as triggering events from the radiological information system (RIS) for image prefetching and visual cues from photo-icons for full-size image retrieval. Concepts such as teleconsultation and remote procedure monitoring are aimed at providing the same level of services at distant sites that would be available in-house. This article highlights the system design parameters that must be considered to engineer a scalable distributed teleradiology system.

California↗
PubMed1994

The role of calcium-binding proteins in selective motoneuron vulnerability in amyotrophic lateral sclerosis.

The factors contributing to selective motoneuron loss in amyotrophic lateral sclerosis (ALS) remain undefined. To investigate whether calcium-binding proteins contribute to selective motoneuron vulnerability in ALS, we compared calbindin-D28K and parvalbumin immunoreactivity in motoneuron populations in human ALS, and in a ventral spinal cord hybrid cell line selectively vulnerable to the cytotoxic effects of ALS IgG. In human autopsy specimens, immunoreactive calbindin-D28k and parvalbumin were absent in motoneuron populations lost early in ALS (i.e., cortical and spinal motoneurons, lower cranial nerve motoneurons), while motoneurons damaged late or infrequently in the disease (i.e., Onuf's nucleus motoneurons, oculomotor, trochlear, and abducens nerve neurons) expressed markedly higher levels of immunoreactive calbindin-D28K and/or parvalbumin. Motoneuron-neuroblastoma VSC 4.1 hybrid cells lost immunoreactive calbindin-D28k and parvalbumin following dibutyryl-cyclic AMP-induced differentiation and were killed by IgG from ALS patients. Undifferentiated calbindin/parvalbumin-reactive VSC 4.1 cells were not killed, nor were other cell lines expressing high levels of calbindin-D28K and parvalbumin immunoreactivity (substantia nigra-neuroblastoma hybrid cells and N18TG2 neuroblastoma parent cells). These studies suggest that decreased calbindin-D28K and parvalbumin immunoreactivity may help explain the selective vulnerability of motoneurons in ALS.

Adult↗
PubMed1993

The effect of irreversible image compression on diagnostic accuracy in thoracic imaging.

RATIONALE AND OBJECTIVES: Digital image compression reduces the storage requirements and network traffic on picture archiving and communications systems. Full-frame bit-allocation (FFBA) is an irreversible image-compression method based on the discrete cosine transform that provides for high compression ratios with a high degree of image fidelity. METHODS: One hundred twenty-two posteroanterior chest radiographs were obtained on patients in an ambulatory patient setting, including 30 cases of interstitial lung disease, 45 images containing combinations of lung nodules (N = 37) or mediastinal masses (N = 39), and 47 normal images containing none of the pathology for which we were testing. The images were digitized (nominal 2 K x 2 K x 12-bit resolution), printed on a 35 x 35-cm hard copy format, and compressed at an approximate compression ratio of 20:1. Observer performance tests were conducted with five radiologists using receiver operating characteristics analysis on digitized uncompressed and compressed hard copy images. RESULTS: There were no significant differences between the two display conditions for the detectability of any of the thoracic abnormalities. CONCLUSIONS: Our preliminary results suggest that irreversible image compression at ratios of 20:1 may be acceptable for use in digital thoracic imaging.

Algorithms↗
PubMed1992

Subperiosteal resorption: effect of full-frame image compression of hand radiographs on diagnostic accuracy.

Image compression is essential to handle a large volume of digital images, including computed tomographic, magnetic resonance, computed radiographic, and digitized images in a digital radiology operation. Developed during the past few years, full-frame bit allocation performed with the cosine transform technique has been proved to be an excellent irreversible image compression method. This article describes the effect, on the accuracy of diagnosis of subperiosteal resorption, of using the hardware compression module to produce hand radiographs. Receiver operating characteristic analysis of the interpretation of 71 radiographs by five observers demonstrated that there is no statistically significant difference in diagnostic accuracy between the original radiographs and compressed and reconstructed images obtained with a compression ratio as high as 20:1.

Bone Resorption↗
PubMed1991

Design and implementation of full-frame, bit-allocation image-compression hardware module. Work in progress.

A hardware module was designed and built to implement the full-frame, bit-allocation image-compression algorithm in a clinical setting. The algorithm transforms an entire image without prepartitioning into small subimages. This adaptation eliminates block artifacts at subimage borders that can mimic relevant pathologic conditions. The quality of 1,024- and 2,048-pixel images compressed at a rate up to 10:1 with a custom-designed processor board (which contains four digital signal processors that transform and quantize separate rows and columns of an image independently with a two-pass cosine transform) and a 16-Mbyte frame buffer was found to be diagnostically acceptable in preliminary receiver operating characteristic studies. The module can compress a 1,024-pixel image in 4 seconds in a general-purpose computer system; images can be compressed in 1 second with the addition of a custom-designed data transporter. Copies of the compression module are being installed in the authors' department and in collaborating hospitals for laboratory and clinical evaluation.

Computers↗
PubMed1989

Role of human immunodeficiency virus type 1-specific protease in core protein maturation and viral infectivity.

It is generally believed that the gag gene product of human immunodeficiency virus type 1 (HIV-1) is processed into several core proteins by a virus-specific protease. We used deletion mutation analysis to study the role of HIV-specific protease in the processing of core proteins and its requirement for viral infectivity. Several mutant genomes with deletions in the protease gene were constructed. A mammalian cell line, COS-M6, transfected with the wild-type viral genome was shown to produce virions containing processed core proteins, while COS-M6 cells transfected with two mutated genomes could express only the core protein precursor, Pr56gag. The wild-type transfectant produced infectious virus; both transfectants expressing the mutated genomes also produced virions, and one of them still retained reverse transcriptase activity. However, the mutant viral particles were devoid of infectivity. Virions with a distinct central core and an electron-dense nucleoid budded out from the plasma membrane of COS-M6 cells transfected with the wild-type genome. In contrast, noninfectious virions that budded either into cytoplasmic vacuoles or out from the plasma membrane of COS-M6 cells transfected with mutant genomes contained ring-shaped nucleoids. These results indicate that the HIV-1 protease plays a role not only in the maturation of the core proteins but also in the assembly of the virus and thus is required for viral infectivity.

Amino Acid Sequence↗