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Biomedical subjects

J Cheung

Publications and source records attributed to J Cheung.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular junction.

Here we describe an important involvement of Cdk5/p35 in regulating the gene expression of acetylcholine receptor (AChR) at the neuromuscular synapse. Cdk5 and p35 were prominently expressed in embryonic muscle, and concentrated at the neuromuscular junction in adulthood. Neuregulin increased the p35-associated Cdk5 kinase activity in the membrane fraction of cultured C2C12 myotubes. Co-immunoprecipitation studies revealed the association between Cdk5, p35 and ErbB receptors in muscle and cultured myotubes. Inhibition of Cdk5 activity not only blocked the NRG-induced AChR transcription, but also attenuated ErbB activation in cultured myotubes. In light of our finding that overexpression of p35 alone led to an increase in AChR promoter activity in muscle, Cdk5 activation is sufficient to mediate the up-regulation of AChR gene expression. Taken together, these results reveal the unexpected involvement of Cdk5/p35 in neuregulin signaling at the neuromuscular synapse.

Animals↗
PubMed2001

Hospital utilisation expectancies in New Zealand, 1980-98.

The need to synthesise mortality and morbidity information to achieve a more global and relevant measure of population health status is well recognised, with health expectancy indices being the most common approach used to date. Using New Zealand hospital discharge and mortality data over the 1980-98 period, we introduce readers to a newly developed health index, the Hospital Utilisation Expectancy (HUE). We describe how HUE changes with age and over time. New Zealand national and regional trends are described. The methodological strengths of the measure and its applications in the health sector are discussed.

Adolescent↗
PubMed2000

Cloning and characterization of muscle-specific kinase in chicken.

Muscle-specific kinase (MuSK) is part of the receptor complex that is involved in the agrin-induced formation of the neuromuscular junction. In the rodent, prominent mRNA expression of MuSK is restricted to skeletal muscle while the expression of agrin can also be detected in brain and certain nonneuronal tissues. The recent identification of Xenopus MuSK reveals that MuSK can be detected in tissues other than skeletal muscle, such as the neural tube, eye vesicles, and spleen. In this study, we describe the cloning and characterization of the chicken ortholog of MuSK and demonstrate that the regulation of MuSK expression in muscle is conserved from avian to rodent. Abundant mRNA expression of MuSK can be detected in early embryonic chick muscle and is up-regulated after nerve injury. More importantly, we also demonstrate that, in the chicken, MuSK mRNA is expressed during development in brain and liver, suggesting possible novel functions for MuSK. Furthermore, the regulatory profile of MuSK expression in chick muscle closely parallels that observed for acetylcholine receptor, in terms of both mRNA expression and protein localization. Finally, studies with paralyzed chicken muscle as well as with cultured chick myotubes demonstrate the dependence of MuSK on both electrical activity and trophic factors.

Animals↗
PubMed2000

Effects of lipids in patients with familial hypercholesterolaemia on the kinetics of the sodium-lithium countertransporter.

Sodium-lithium countertransport kinetics were measured in 87 patients (50 male; 37 female) with heterozygous familial hypercholesterolaemia (FH) and a group of 38 age range and sex-distribution matched controls. Basic clinical data including basic anthropometry, blood pressure were obtained and blood was taken for detailed lipid biochemistry, glucose and insulin measurement. Patients with FH had elevated total cholesterol, low-density lipoprotein (LDL)-cholesterol and apolipoprotein B concentrations compared to controls. The activity and log transformed maximal velocity (Vmax) of the sodium-lithium countertransporter unlike the affinity (Km) were reduced in patients with FH compared to controls (geometric means 0.172 vs 0.217 mmol Li+/L.RBC.hr; P = 0.02; 0.237 vs. 0.317 mmol Li+/L.RBC.hr; P = 0.009 respectively). In multiple regression analysis, log normalised SLC activity correlated weakly with log triglyceride (beta = 0.225; P = 0.06) and cholesterol (beta = -0.112 P = 0.06). Log Vmax correlated with log triglyceride (beta = 0.307; P = 0.02), and high-density lipoprotein (HDL) (beta = 0.74; P = 0.03) whilst Km correlated with HDL (beta = 1.73; P<0.001) and apoAI (beta = -1.76; P = 0.0048), LDL (beta = -0.14; P = 0.05), and creatine kinase (beta = 0.003; P = 0.01). Cholesterol and triglyceride concentrations rather than insulin resistance seem to be the key features affecting the environmental alteration of sodium lithium countertransporter Vmax in patients with familial hypercholesterolaemia.

Adult↗
PubMed1999

Inhibition of glutathione S-transferase zeta and tyrosine metabolism by dichloroacetate: a potential unifying mechanism for its altered biotransformation and toxicity.

Dichloroacetate (DCA) inhibits its own metabolism and is converted to glyoxylate by glutathione S-transferase zeta (GSTz). GSTz is identical to maleylacetoacetate isomerase, an enzyme of tyrosine catabolism that converts maleylacetoacetate (MAA) to fumarylacetoacetate and maleylacetone (MA) to fumarylacetone. MAA and MA are alkylating agents. Rats treated with DCA for up to five days had markedly decreased hepatic GSTz activity and increased urinary excretion of MA. When dialyzed cytosol obtained from human liver was incubated with DCA, GSTz activity was unaffected. In contrast, DCA incubation inhibited enzyme activity in dialyzed hepatic cytosol from rats. Incubation of either rat or human hepatic cytosol with MA led to a dose dependent inhibition of GSTz. These data indicate that humans or rodents exposed to DCA may accumulate MA and/or MAA which inhibit(s) GSTz and, consequently, DCA biotransformation. Moreover, DCA-induced inhibition of tyrosine catabolism may account for the toxicity of this xenobiotic in humans and other species.

Animals↗
PubMed1999

Independent life expectancy in New Zealand, 1996-97.

The objective of this article is to describe independent life expectancy (ILE) in New Zealand in 1996-97, including variations in this indicator between age, gender and ethnic groups. ILE is defined as the number of years a person can expect to live without any self-reported functional limitation requiring the assistance of another person or a complex assistive device. ILE is a positive measure of health. Its complement, expectation of life with dependency (LED), is also a useful indicator. Together, ILE and LED add up to total life expectancy (LE). The contribution to ILE from disability and mortality at each age is analysed in this article. The elasticity of ILE to changes in mortality and to changes in disability is also investigated. Finally, the burden of injury is estimated by calculating the potential gain in ILE that would result were injury-related disability and mortality to be eliminated.

Activities of Daily Living↗
PubMed1999

Novel terpenoid-type quinones isolated from Pycnanthus angolensis of potential utility in the treatment of type 2 diabetes.

Using an ethnomedical-based drug discovery program, two previously unknown compounds (SP-18904 and SP-18905) from Pycnanthus angolensis were isolated that lower glucose concentrations in mouse models of type 2 diabetes. SP-18904 and SP-18905 are terpenoid-type quinones that significantly lowered plasma glucose concentration (p <.05) when given orally to either ob/ob or db/db mice, both of which are hyperglycemic and hyperinsulinemic. The antihyperglycemic actions of SP-18904 and SP-18905 were associated with significant decreases in plasma insulin concentrations (p <.05), suggesting that both compounds lowered glucose by enhancing insulin-mediated glucose uptake. This was supported by the insulin suppression test in ob/ob mice. Studies in hyperglycemic, insulin-deficient mice and in vitro experiments on 3T3-L1 adipocytes further supported this conclusion. As such, these two terpenoid-type quinones represent a new class of compounds of potential use in the treatment of type 2 diabetes.

Adipocytes↗
PubMed1998

Masoprocol (nordihydroguaiaretic acid): a new antihyperglycemic agent isolated from the creosote bush (Larrea tridentata).

An ethnomedically-driven approach was used to evaluate the ability of a pure compound isolated from the creosote bush (Larrea tridentata) to lower plasma glucose concentration in two mouse models of type 2 diabetes. The results indicated that plasma glucose concentration fell approximately 8 mmol/l in male C57BL/ks-db/db or C57BL/6J-ob/ob mice following the oral administration of masoprocol (nordihydroguaiaretic acid), a well known lipoxygenase inhibitor. The decline in plasma glucose concentration following masoprocol treatment in the mice was achieved without any change in plasma insulin concentration. In addition, oral glucose tolerance improved and the ability of insulin to lower plasma glucose concentrations was accentuated in masoprocol-treated db/db mice. These data raise the possibility that masoprocol, or other lipoxygenase inhibitors, represents a new approach to the pharmacological treatment of Type 2 diabetes.

Animals↗
PubMed1998

Caring as the ontological and epistemological foundations of nursing: a view of caring from the perspectives of Australian nurses.

In a study using unstructured interviews to explore nurses' understanding and interpretations of caring in nursing, one of the major themes emerging from the data is that through caring for patients, nurses discover the meaning and nature of nursing and what it means for them to be nurses. In the process of caring for patients, nurses further develop and understand the knowledge and skill of caring which constitutes the knowledge base of nursing. The data also show that nurses, in their practice, continue to define, develop and shape the meaning and knowledge of caring in nursing. From the evidence of this study, this paper argues that caring can be considered as the ontological and epistemological foundations of nursing.

Adult↗
PubMed1998

Biochemistry and regulation of a novel Escherichia coli K-12 porin protein, OmpG, which produces unusually large channels.

A novel porin, OmpG, is produced in response to a chromosomal mutation termed cog-192. Molecular characterization of cog-192 revealed that it is a large chromosomal deletion extending from the 3' end of pspA through to the 5' end of an open reading frame located immediately upstream of ompG. As a result of this 13.1-kb deletion, the expression of ompG was placed under the control of the pspA promoter. Characterization of OmpG revealed that it is quite different from other porins. Proteoliposome swelling assays showed that OmpG channels were much larger than those of the OmpF and OmpC porins, with an estimated limited diameter of about 2 nm. The channel lacked any obvious solute specificity. The folding model of OmpG suggests that it is the first 16-stranded beta-barrel porin that lacks the large external loop, L3, which constricts the channels of other nonspecific and specific porins. Consistent with the folding model, circular dichroism showed that OmpG contains largely a beta-sheet structure. In contrast to other Escherichia coli porins, there is no evidence that OmpG exists as stable oligomers. Although ompG DNA was present in all E. coli strains examined so far, its expression under laboratory conditions was seen only due to rare chromosomal mutations. Curiously, OmpG was constitutively expressed, albeit at low levels, in Salmonella, Shigella, and Pseudomonas species.

Amino Acid Sequence↗