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J K Li

Publications and source records attributed to J K Li.

At least 55 records · Page 3Linked to original sources
PubMed1996

Computer modeling of non-adjacent regional ischemic zones on ventricular function.

Multiple regional myocardial ischemia that leads to depressed left ventricular (LV) function is commonplace. Quantitative analysis of the hemodynamic consequences, however, has been limited. We investigated this aspect using a novel computer model of the cardiovascular system. The model consists of an LV with two ischemic zones (IZs) and a normal zone (NZ), the preload, and the arterial system afterload. The IZ size and activation timing could be altered. Results show that the greater the size and activation asynchronization between NZ and IZ, the more severe the LV dysfunction. Increased preload during ischemia improved LV function. This computer model predicts features that agree well with reported experimental observations and is particularly useful for myocardial ischemic function analysis.

Animals↗
PubMed1996

Thyrotoxic periodic paralysis in a Chinese population.

We retrospectively evaluated the characteristics of adult patients admitted with thyrotoxic hypokalaemic periodic paralysis in Hong Kong. From 1984 to 1993, 45 Chinese adult patients were admitted with acute limb weakness, plasma potassium < or = 3.5 mmol/l and thyrotoxicosis confirmed by laboratory investigations. All but one were male. Seventy-five percent of attacks occurred between 9pm and 9am. Half of the attacks occurred between July and October (49.1%), most commonly in August (20%). Mean (+/- SEM) plasma potassium on admission was 2.17 +/- 0.08 mmol/l (range 1.1-3.5). In 15 episodes (27.3%), plasma potassium on recovery exceeded 5.0 mmol/l, while in three episodes (5.5%), potassium exceeded 6.0 mmol/l. No patient had a positive family history of thyrotoxic periodic paralysis. Only 28.9% had a known history of thyrotoxicosis before their first presentation with periodic paralysis. Twenty-seven (60%) had clinical evidence of thyrotoxicosis. Although all were biochemically thyrotoxic, 11.4% had only a mild degree of thyrotoxicosis (suppressed thyroid-stimulating hormone, high free thyroxine, but normal free triiodothyronine). One quarter of the patients had a normal erythrocyte zinc concentration, indicating either a short history of thyrotoxicosis or transient thyrotoxicosis. The diagnosis of thyrotoxic hypokalaemic paralysis should always be considered in Chinese patients with acute muscle weakness, especially in young males. Absence of clinical thyrotoxicosis does not exclude the diagnosis. Plasma potassium should be monitored carefully during treatment to prevent rebound hyperkalaemia.

Adult↗
PubMed1996

Modeling of mechanical dysfunction in regional stunned myocardium of the left ventricle.

Reversible mechanical dysfunction of the myocardium after a single or multiple episode(s) of coronary artery occlusion has been observed in previous studies and is termed myocardial stunning. The hypothesis that stunning could be represented by a decrease in maximum available muscle force in the stunned region was examined by means of a mathematical model that incorporates series viscoelastic elements. A canine experimental model was also employed to demonstrate depressed contractility and a consistent delay of shortening in the stunned region. The mechanical model of the left ventricle was designed to include a normal and stunned region, for which the stunned region was allowed to have variable size. Each region consisted of a volume and time dependent force generator in parallel with a passive elastic force element. The passive elastic element was placed in series with a constant viscosity component and a series elastic component. The model was solved by means of a computer. Passive and active properties of each region could be altered independently. The typical regional measures of muscle performance such as percent shortening, percent bulge, percent thickening, delay of shortening, percent increase in end-diastolic length and other hemodynamic measures were computed. These results were similar to those observed in animal models of stunning. In addition, a nearly linear relationship with end-diastolic length and delay of shortening was predicted by the model. It was concluded that a decrease in the peak isovolumic elastance and augmentation of viscosity effect of creep during stunning can explain mechanical abnormalities of stunned myocardium.

Analysis of Variance↗
PubMed1996

Unstable radii in muscular blood vessels.

A model of a muscular blood vessel in equilibrium that predicts stable and unstable control of radius is presented. The equilibrium wall tension is modeled as the sum of a passive exponential function of radius and an active parabolic function of radius. The magnitude of the active tension is varied to simulate the variable level of smooth muscle activation. This tension-radius relationship is then converted to an equilibrium pressure-radius relationship via Laplace's law. This model predicts the traditional ability to control the radius below a critical level of activation. However, when the active tension is raised above this critical level, the pressure-radius relationship (with pressure plotted on the ordinate and radius on the abscissa) becomes N shaped with a relative maximal pressure (Pmax) and a relative minimal pressure (Pmin). For this N-shaped curve, there are three equilibrium radii for any pressure between Pmin and Pmax. Analysis shows that the middle radius is unstable and thus cannot be maintained at equilibrium. Previously unexplained experimental data reveal evidence of this instability.

Animals↗
PubMed1996

Serum bilirubin and cardiovascular risk factors in a Chinese population.

BACKGROUND: Many risk factors for cardiovascular disease (CVD) have been identified. Recently an association between low concentration of serum bilirubin and increased risk of CVD has been reported. However, information on this topic remains scarce. METHODS: We examined the relationships between serum bilirubin and CVD risk factors in 1508 Hong Kong Chinese. We divided the subjects into four quartiles based on serum bilirubin concentrations. Cardiovascular risk factors studied include age, sex, smoking, obesity glycaemic status and lipid indices. RESULTS: Decreasing serum bilirubin concentration was associated with older age, increased prevalence of smoking, higher body mass index and systolic blood pressure, increased glycated haemoglobin, fasting and 2 h insulin, triglyceride, very-low-density lipoprotein and apolipoprotein B concentrations, and lower high-density lipoprotein concentration. Women had lower bilirubin concentrations than men. After adjustment for age, sex, smoking and insulin levels as covariates, the associations between serum bilirubin concentration and glycated haemoglobin, triglyceride, high-density lipoprotein and very-low-density lipoprotein persisted. The prevalence rates of abnormal glucose tolerance (impaired glucose tolerance or diabetes) were similar amongst the four quartiles of bilirubin concentrations. However, the mean bilirubin concentration was significantly lower in subjects with abnormal glucose tolerance (9.3 +/- 3.5 mumol/l, n = 178) than in normal subjects (10.1 +/- 5.2 mumol/l, n = 1330, P = 0.039). When analysed as a continuous variable by age-adjusted partial correlation coefficients, serum bilirubin concentration was inversely correlated with fasting insulin, triglyceride, very-low-density lipoprotein and glycated haemoglobin level. CONCLUSIONS: There were close associations between low serum bilirubin concentration and increased CVD risk factors. Subjects with abnormal glucose tolerance also had lower serum bilirubin concentration than normal subjects. Some of these associations (body mass index, systolic blood pressure) could be explained by differences in insulin level. These relationships between bilirubin and CVD risk factors require further clarification, although abnormal intermediary metabolism and antioxidant deficiency may be possible linking factors.

Adult↗
PubMed1995

Sequence analyses and antigenic epitope mapping of the putative RNA-directed RNA polymerase of five U.S. bluetongue viruses.

We determined the complete nucleotide sequences of the cognate L1 double-stranded RNA segments of bluetongue virus (BTV) serotypes 2, 11, 13, and 17, which encode the putative RNA-directed RNA polymerase VP1. Each L1 gene contained 3944 nucleotides and was 10 bases shorter than the previously reported L1 gene of BTV 10. A single open reading frame which could encode the reported VP1 protein, 1302 amino acids in size, began with an initiation codon at nucleotides 12-14 and a termination codon at nucleotides 3918-3920. Analyses of the nucleotides of L1 genes and the deduced amino acid sequences of VP1 proteins of the five U.S. BTV serotypes indicated that the most recently isolated BTV-2 serotype from Florida was more distantly related than BTV-10, 11, 13, and 17, which were isolated primarily in the western U.S.A. The results are consistent with our hypothesis that BTVs-10, -11, -13, and -17 are derived from a single and common gene pool, and that BTV-2 belongs to a second, distinct gene pool. These genetic distinctions also reflected well with the known geographic distribution of the five U.S. BTV serotypes in North America. This putative RNA-directed RNA polymerase (149 KDa) was a basic protein, and the deduced amino acid sequences of the VP1 proteins contained seven highly conserved hydrophobic domains and many other sequence motifs which were also found in other known RNA polymerases. Four immunodominant but linear antigenic epitopes conserved among the VP1 of five U.S. BTVs were also been identified and mapped using monospecific oligoclonal antibodies.

Amino Acid Sequence↗
PubMed1994

Characterization of heterologously expressed recombinant retinoic acid receptors with natural or synthetic retinoids.

The first step in retinoid action is binding to their nuclear receptors. Therefore, characterization of binding characteristics of retinoids is of major importance. Human retinoic acid receptors alpha (hRAR alpha), hRAR beta, and mouse RAR gamma (mRAR gamma) were expressed heterologously in Escherichia coli as a recombinant glutathione S-transferase (GST) fusion protein. The expressed fusion proteins were functional and bound specifically to the all-trans-retinoic acid (RA). The dissociation constants (Kd) for RA were 1.4 nM for GST-hRAR alpha, 1.4 nM for GST-hRAR beta, and 3.3 nM for GST-mRAR gamma, respectively. The fusion proteins were further used for competitive displacement assays to determine the displacement constant (DC50) for other selected retinoids. All-trans-RA and 4-oxo-all-trans-RA have high affinity with all three receptors (DC50 = 0.8-55 nM). The 13-cis RA binds to hRAR alpha with low affinity, but not to other RARs evaluated here. All-trans-N-ethylretinamide, all-trans-retinylacetate, and an ethyl ester of tetrahydronaphthalene derivative had no affinity to any RARs. The hRAR alpha and mRAR gamma receptors did not bind a naphthalene carboxylic acid derivative of RA, but hRAR beta binds this chemical with high affinity. Results indicated that the three recombinant proteins were functional in binding various RA congeners. The affinity and binding data of these retinoids were compared to their observed teratogenic activity.

Amino Acid Sequence↗
PubMed1994

Analyses and conservation of sequences among the cognate L3 segments of the five United States bluetongue viruses.

We determined the complete nucleotide sequences of the cognate L3 double-stranded RNA (ds-RNA) segments of bluetongue virus (BTV) serotypes 2, 11, and 13 encoding the major viral inner capsid protein, VP3. Each cognate L3 segment was 2772 nucleotides long and contained a single open reading frame (ORF) with an initiation codon at nucleotides #18-20 and a termination codon at nucleotides #2721-2723. This ORF can encode the 901-amino acid VP3 protein (103 kDa) with a calculated isoelectric point of 6. Phylogenetic analyses using both the nucleotide and the deduced amino acid sequences of the L3 cognate gene of the five US BTV serotypes indicated that the BTV-2 serotype recently isolated in Florida was more distantly related than BTV-10, 11, 13 or 17. The five US BTV serotypes were derived apparently from two distinct gene pools, findings consistent with their current geographic distribution in North America.

Amino Acid Sequence↗
PubMed1994

Mapping and characterization of antigenic epitopes and the nucleic acid-binding domains of the VP6 protein of bluetongue viruses.

Heterologously expressed VP6 and truncated VP6 proteins of bluetongue virus (BTV) serotype 11 purified to near homogeneity were used for structure and function analyses. The yield of the expressed VP6 was host cell dependent. Six antigenic epitopes of VP6 of BTV were identified and mapped by immunoblot analyses and enzyme-linked immunosorbent assay with oligoclonal antibodies. These determinants were surface accessible and conserved among the cognate VP6 proteins of five U.S. BTV serotypes. The amino acid sequences and sizes of these six antigenic epitopes were determined, and their precise locations were also mapped and confirmed by deletion analyses. The nucleic acid binding activities of VP6, confirmed by electrophoretic mobility shift assay, were concentration dependent. The binding activities and affinities of the purified expressed VP6 protein towards double-stranded RNA and double-stranded DNA were similar. Two domains of VP6, corresponding to three of the six antigenic epitopes, were responsible for the nucleic acid binding activities and have been mapped within 28 amino acids near the middle and 11 residues near the carboxyl terminus of VP6 by electrophoretic mobility shift assay and deletion mutant analyses. Synthetic oligopeptides corresponding to these three regions also exhibited similar concentration-dependent nucleic acid binding activities.

Amino Acid Sequence↗
PubMed1994

Pathogenesis of gall stones in Crohn's disease: an alternative explanation.

The increased prevalence of gall stones in Crohn's disease is thought to be related to depletion of the bile salt pool due either to terminal ileal disease or after ileal resection. This study was designed to examine whether this hypothesis is correct and explore alternative explanations. Two hundred and fifty one randomly selected patients (156 females, 95 males, mean age 45 years) were interviewed and screened by ultrasonography to determine the prevalence of gall stones in a large population of patients with Crohn's disease. Sixty nine (28%) patients had gall stones proved by ultrasonography (n = 42), or had had cholecystectomy for gall stone disease (n = 27). The risk factors for the development of gall stones including sex, age, site, and duration of disease, and previous intestinal resection were examined by multivariate analysis. Age and duration of disease were positive risk factors for gall stones and were covariables. The site of disease and of previous intestinal resection did not predispose to gall stones. Previous surgery was an independent risk factor for the development of gall stones, the risk increasing with number of laparotomies. It is suggested that mechanisms other than ileal dysfunction may predispose to gall stones. Postoperative gall bladder hypomotility with biliary sludge formation may be precursors of gall stone formation in patients with Crohn's disease.

Adolescent↗
PubMed1994

Differential effects of wave reflections and peripheral resistance on aortic blood pressure: a model-based study.

It has been generally accepted that arterial system wave reflections act to increase aortic blood pressure and the load placed on the left ventricle. Using a mathematical model of the coupled left ventricle-arterial system, we predict that this is not the case. With the model, two aspects of wave reflection, the global reflection coefficient [TG(omega)] and the pulse wave velocity (cph), were adjusted independently. In addition, TG(omega) and cph could be altered independently of the direct-current properties of the arterial system model. Reduction of TG(omega) yielded increases in stroke volume (SV) as well as in peak systolic (Ps), diastolic (Pd), and mean aortic (Pao) pressures and, hence, increased the load on the left ventricle. SV and Pao increased only in the range where strong reflection occurs. Reduced cph also yielded higher pressures, whereas increased cph resulted in reduced Pao and Pd but increased Ps. The changes in pressures and SV in response to altered TG(omega) and cph were relatively small compared with absolute levels. Simulated vasoconstriction and vasodilation further demonstrated the much greater importance of peripheral resistance on pressure and SV levels and lead to the prediction that pressure reduction in vasodilation occurs not because of, but in spite of, reduced wave reflections. We conclude that these results have not yet been observed experimentally, because reflection cannot yet be separated from the direct-current properties of the arterial system; therefore wave reflections themselves have not yet been adequately studied in the intact animal.

Animals↗
PubMed1994

Arterial compliance and its pressure dependence in hypertension and vasodilation.

Arterial compliance has been recognized to be pressure-dependent. Its variation due to changing systolic and diastolic blood pressures in hypertension and subsequent vasodilation has not been investigated. The authors examined this aspect by combining an animal experiment and a recently established nonlinear windkessel model of the arterial system that incorporates a pressure-dependent arterial compliance, C(P). Aortic pressure and flow were simultaneously measured in experimental dogs during control and during methoxamine-induced hypertension and nitroprusside-induced vasodilation. A numerical procedure was implemented to compute the nonlinear compliance and account for the pressure dependence. Results show that within the cardiac cycle, C(P) reached its maximum at end-systole and increased in diastole when diastolic aortic pressure decayed. The magnitude of C(P) and its variation within the cardiac cycle was larger at low pressures, while the reverse was found when blood pressure was high. C(P) decreased significantly in hypertension and increased during subsequent vasodilation.

Animals↗
PubMed1993

High-sequence conservation among the United States bluetongue viruses cognate M2 genes which encode the nonstructural NS1 tubule protein.

Full-length cDNA copies of the M2 gene of BTV-2, -11, and -13 serotypes obtained by a modified polymerase chain reaction (Clamp-R) were cloned into pUC19 plasmid. The entire nucleotide sequences of each M2 gene were determined and compared with BTV-10 and BTV-17, thus completing the sequencing of these cognate M2 gene segments from all five U.S. BTV serotypes. Each M2 segment contained 1769 nucleotides, a single open reading frame (ORF) with an initiation codon at nucleotides 35-37, and a termination codon at nucleotides 1691-1693. This ORF can encode the 552-amino-acid NS1 protein (64 KDa) which has an isoelectric point of 7. Analyses of the nucleotide and deduced amino acid sequences of the five U.S. BTV serotypes indicated that the most recently isolated BTV-2 serotype was more distantly related than BTV-10, -11, -13, or -17. Analyses of the evolutionary relatedness of the cognate M2 genes by codon positions indicate that the rate of mismatch accumulations in the first and second base codon positions are less than 4%. However, the mismatch accumulations in the third base codon position are quite evident (23%) when BTV-2 serotype was compared with the other U.S. BTV serotypes. This suggests that BTV-2 has separated from the other four U.S. serotypes long before they themselves diverged. These data also indicate that the five U.S. BTV serotypes were apparently derived from two distinct gene pools that reflected geographic distribution in North America.

Base Sequence↗
PubMed1993

Conservation of the segment 4 gene sequence and of a leucine zipper motif in VP4 among five US bluetongue viruses.

Full-length cDNA copies of the segment 4 (M1) genes of US Bluetongue viruses serotype-2, -10, -11, -13, and -17 were selectively amplified using genomic double-stranded RNA segments from purified BTV virions as templates and a modified polymerase chain reaction (Clamp-R). They were then cloned into pUC19 plasmids and both strands of several clones were sequenced. The length of all five segment 4 genes is 1981 nucleotides, which is 30 nucleotides shorter than that of the BTV serotype-10 reported by Y. Yu, A. Fukusho, and P. Roy (Nucleic Acids Res. 15, 7206 (1987)). The 5'- and 3'-noncoding regions of all five segment 4 genes are identical among all serotypes. The plus sense strand of the BTV segment 4 gene, which encodes the VP4 protein, possesses a single long open reading frame with an initiation codon (ATG) at nucleotides 9-11 and a stop codon (TAA) at nucleotides 1941-1943. This open reading frame encodes for a protein of 644 amino acid residues with a predicted molecular weight of about 75 kDa and a pI of +7 to +7.9. A potential leucine zipper motif was detected near the carboxyl terminus of the deduced VP4 amino acid sequence. The phylogenetic analysis using the sequences of these five cognate segment 4 genes is consistent with the results of our previous phylogenetic studies of cognate genome segments 5, 6, 8, 9, and 10. Serotype-10, -11, -13, and -17 are closely related and serotype-2 is the most distantly related among the five US BTV serotypes.

Amino Acid Sequence↗
PubMed1993

Identification and localization of a serotypic neutralization determinant on the VP2 protein of bluetongue virus 13.

We have used a serotype-specific monoclonal antibody to locate a neutralization epitope on the outer capsid protein, VP2, of the bluetongue virus 13. This surface-accessible region of the virion was recognized by a monoclonal antibody, D24.15, which exhibited serotype-specific neutralizing activity as determined by plaque reduction assay. In Western blots, this monoclonal antibody reacted only with the VP2 of bluetongue virus 13, but not with any of the other US BTV serotypes. Competition with sequence-specific synthetic peptides identified only one linear synthetic peptide (EMDD-DETEYE), corresponding to amino acids 642-651 of VP2 of bluetongue virus 13 that could block both the neutralizing activity of MAb D24.15 and its specific binding to VP2 of BTV-13. However, oligoclonal antibody against this synthetic peptide did not exhibit any neutralizing activity. These data suggest that the serotype-specific neutralization determinant of the outer capsid protein VP2 is located on the surface of the BTV-13 virion and represents the major component of a conformational epitope.

Amino Acid Sequence↗
PubMed1993

Feedback effects in heart-arterial system interaction.

Dynamic arterio-ventricular interaction in terms of left ventricle elastance and nonlinear arterial system compliance, pulse wave reflections and coronary blood flow was investigated, combining the use of analog models of the circulation with data from animal experiments. Results show that dynamic factors, as well as "feedback" effects are important.

Animals↗