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Biomedical subjects

H Y Chan

Publications and source records attributed to H Y Chan.

32 records · Page 2Linked to original sources
PubMed2000

Housing quality and mental health.

This study examined the potential link between housing quality and mental health. First, the development of a psychometrically sound, observer-based instrument to assess physical housing quality in ways conceptually relevant to psychological health is reported. Then 2 different studies, including a prospective longitudinal design, demonstrate that physical housing quality predicts mental health. Possible underlying psychosocial processes for the housing quality-psychological distress link are discussed.

Adult↗
PubMed2000

Drosophila models of human neurodegenerative disease.

Drosophila has provided a powerful genetic system in which to elucidate fundamental cellular pathways in the context of a developing and functioning nervous system. Recently, Drosophila has been applied toward elucidating mechanisms of human neurodegenerative disease, including Alzheimer's, Parkinson's and Huntington's diseases. Drosophila allows study of the normal function of disease proteins, as well as study of effects of familial mutations upon targeted expression of human mutant forms in the fly. These studies have revealed new insight into the normal functions of such disease proteins, as well as provided models in Drosophila that will allow genetic approaches to be applied toward elucidating ways to prevent or delay toxic effects of such disease proteins. These, and studies to come that follow from the recently completed sequence of the Drosophila genome, underscore the contributions that Drosophila as a model genetic system stands to contribute toward the understanding of human neurodegenerative disease.

Amyloid beta-Protein Precursor↗
PubMed2000

The Drosophila embargoed gene is required for larval progression and encodes the functional homolog of schizosaccharomyces Crm1.

The CRM1 (Exportin 1) protein is a receptor for leucine-rich nuclear export signal sequences. We have molecularly characterized the Drosophila melanogaster embargoed (emb) gene and find that it encodes a product with 49 and 71% sequence identity to the fission yeast Schizosaccharomyces pombe and human CRM1 proteins, respectively. We show that expression of the emb cDNA is sufficient to suppress the growth phenotype of both conditional-lethal and null S. pombe crm1(-) mutant strains, suggesting that emb encodes the functional homologue of the S. pombe Crm1 protein. Through mutagenesis screens we have recovered a series of recessive lethal emb mutations. There is a substantial maternal contribution of emb mRNA and animals hemizygous for our emb alleles can develop to second instar larvae but persist at this stage and consistently fail to undergo the molt to the third instar stage. We see a nuclear accumulation of endogenous actin in the intestinal epithelial cells of the emb mutant larvae, consistent with a role for the emb gene product in nuclear export of actin protein.

Actins↗
PubMed1999

Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70.

At least eight inherited human neurodegenerative diseases are caused by expansion of a polyglutamine domain within the respective proteins. This confers dominant toxicity on the proteins, leading to dysfunction and loss of neurons. Expanded polyglutamine proteins form aggregates, including nuclear inclusions (NI), within neurons, possibly due to misfolding of the proteins. NI are ubiquitinated and sequester molecular chaperone proteins and proteasome components, suggesting that disease pathogenesis includes activation of cellular stress pathways to help refold, disaggregate or degrade the mutant disease proteins. Overexpression of specific chaperone proteins reduces polyglutamine aggregation in transfected cells, but whether this alters toxicity is unknown. Using a Drosophila melanogaster model of polyglutamine disease, we show that directed expression of the molecular chaperone HSP70 suppresses polyglutamine-induced neurodegeneration in vivo. Suppression by HSP70 occurred without a visible effect on NI formation, indicating that polyglutamine toxicity can be dissociated from formation of large aggregates. Our studies indicate that HSP70 or related molecular chaperones may provide a means of treating these and other neurodegenerative diseases associated with abnormal protein conformation and toxicity.

Animals↗
PubMed1999

Synchronous and asynchronous brain-state-in-a-box information system neural models.

Synchronous and asynchronous information system neural models are proposed that are hybrids of Pawlak's information system and Brain-State-in-a-Box (BSB) neural models. The stability of the proposed models is studied using LaSalle's Invariance Principle. Applications to an analysis of the United Nations activities are presented as examples.

Information Systems↗
PubMed1998

Identification and characterization of the gene for Drosophila L3 ribosomal protein.

A cDNA clone that encodes a Drosophila homologue of ribosomal protein L3 was isolated from a Drosophila ovary gridded cDNA library. The Drosophila ribosomal protein L3 gene (RpL3) is highly conserved with ribosomal protein L3 genes in other organisms. It is a single copy gene and maps to position 86D5-10 on polytene chromosomes. A Minute gene in this region, M(3) 86D, is a possible candidate to encode RPL3. RPL3 message is expressed ubiquitously. A partial RPL8 cDNA clone was also isolated and mapped to 62F.

Amino Acid Sequence↗
PubMed1997

Endothelial cell-specific expression of tumor necrosis factor-alpha from the KDR or E-selectin promoters following retroviral delivery.

The tumor vasculature offers a target for anti-cancer gene therapy which has the advantages both of good accessibility to systemically delivered therapy and comparative homogeneity across solid tumor types. We aimed to develop retroviruses carrying endothelial-specific promoters for the delivery of genes to proliferating endothelial cells in vitro and to tumor endothelial cells in vivo. This paper reports the generation of such retroviral vectors and the level of expression of murine tumor necrosis factor-alpha (mTNF-alpha) cDNA following infection into endothelial cells and stromal fibroblasts. Retroviral vectors carrying mTNF-alpha have been generated whose expression is controlled either by the retroviral long terminal repeat or by 5' proximal promoter sequences from the endothelial-specific kinase insert domain receptor (KDR)/VEGF receptor and E-Selectin promoters within the context of a self-inactivating (SIN) vector backbone. Both KDR and E-Selectin have been shown to be upregulated on tumor endothelium. A putative polyadenylation sequence AAATAAA within the E-Selectin promoter was mutated to permit faithful transmission of retroviral vectors carrying this promoter. We demonstrate a 10- to 11-fold increase in mTNF-alpha expression from promoter elements within sEND endothelioma cells as compared to NIH-3T3 fibroblasts. Suggestions for further improvements in vector design are discussed.

3T3 Cells↗
PubMed1997

Identification and characterization of the gene for Drosophila S20 ribosomal protein.

A cDNA clone that encodes a Drosophila homologue of ribosomal protein S20 was isolated from a Drosophila ovary cDNA library. The Drosophila S20 gene (RpS20) is highly conserved with S20 genes in other organisms. It is a single copy gene and maps to position 92F-93A on polytene chromosomes. No Minute mutation in this location has been reported; at least five essential genes are possible candidates to encode RpS20. RpS20 message is expressed ubiquitously in embryos, but is expressed at high levels in the midgut.

Amino Acid Sequence↗
PubMed1994

Incorporating production rules with spatial information onto a neocognitron neural network.

Rule-embedded neocognitron (REN) is proposed where the knowledge base of a neocognitron is constructed through incorporating production rules into its interlayer connections. Prototype patterns training is not required. The semantic of interlayer connections is established. The resulting network can now be analyzed according to the rule structure and problematic portions can be corrected. We demonstrate the ease with which performance can be improved by applying REN on handwritten numeral recognition. The same set of handwritten numerals initiated by Fukushima is used to test this methodology. It is found that the performance is comparable with that of Fukushima's neocognitron with supervised training.

Algorithms↗
PubMed1994

A hybrid cognitive system using production rules to synthesize neocognitrons.

A hybrid cognitive system is proposed where a working neocognitron is synthesized with a set of production rules. The knowledge base of a neocognitron is constructed through incorporating production rules into its interlayer connections. Training for prototype patterns is not required. The semantic of interlayer connections is established. The resulting network can now be analyzed according to the rule structure and problematic portions can be corrected. Neocognitrons constructed using this hybrid approach have been tested on the same set of handwritten numerals initiated by Fukushima with scaling and skewing distortions, and with noise contamination. It is found that the performance is comparable to that of Fukushima's network obtained by supervised training.

Cognition↗
PubMed1990

Detection of extrinsic bronchial compression during foreign body removal by pulse oximetry.

A case of stridor is described which was due to the presence of a foreign body in the larynx of an infant. Following partial removal, compression of the right main bronchus was detected because of continuing low arterial oxygen saturation. The use of pulse oximetry allowed this complication to be identified, and the advantages of this method of monitoring are discussed.

Airway Obstruction↗
PubMed1990

Sucrose synthase in rice plants : growth-associated changes in tissue specific distributions.

Different parts of the rice (Oryza sativa L.) plant at different growth stages were analyzed for sucrose synthase (SS) by enzyme activity assay and enzyme-linked immunosorbent assay directly on the extracts or on the eluates from a gel filtration column. On a dry matter basis, the amount of soluble protein and SS activity decreased significantly, but the amount of enzyme protein changed little in growing leaves. In the grain, the SS activity was the highest at the early ripening stage and decreased later, but the amount of SS protein increased with the increase in maturity. In the root, a low activity of SS was detectable only in the tillering but not in other stages. Immunoblotting of SS protein extracted from different parts of rice showed two bands. Elution patterns of crude extracts from a gel filtration column showed the presence of several types of SS protein. Among them, two to three types with larger elution volumes had the SS activity but others with smaller elution volumes (considered as the aggregated forms) had no activity. The SS purified from different parts of the plant showed similar but distinctly different electrophoretic mobilities in a native gel. It has been concluded that different isozymes are expressed in different tissues at different growth stages.

Journal Article↗
PubMed1987

High-dose VP-16 with intermediate-dose cytosine arabinoside in the treatment of relapsed acute nonlymphocytic leukemia.

In a study of 11 adult patients with acute nonlymphocytic leukemia (ANLL), infusion therapy with high-dose VP-16 and intermediate-dose cytosine arabinoside was administered. Response was assessed with reference to bone marrow aspirations performed on days 1; 12, 13, or 14; and 21 of treatment. All 7 of the patients with ANLL in relapse achieved marrow hypoplasia, and 3 of them achieved complete response. LFTs were elevated in most patients but no evidence of hepatocellular necrosis was observed. It is concluded that the value of VP-16 in ANLL may have been underestimated in the past because of inadequate dosing.

Acute Disease↗