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Biomedical subjects

J K Li

Publications and source records attributed to J K Li.

At least 19 recordsLinked to original sources

A new description of arterial function: the compliance-pressure loop.

Hypertension and atherosclerosis are associated with reduced arterial compliance, which is the principal component that reflects the dynamic behavior of the arterial system. Hence, change in arterial compliance has been used as a compass of arterial wall properties, as well as an effective parameter for assessing therapeutic treatment efficacy. The arterial compliance-blood pressure loop concept is introduced here for assessment of arterial function. Aortic pressure and flow were measured in experimental dogs during normal and acute hypertension. The compliance-pressure loops were constructed from pulsatile blood pressure waveforms and the corresponding compliances. The features of the loop are that, for any given heart beat, arterial compliance is seen to be maximal in early systole to facilitate ventricular ejection, compliance decreasing during the remainder of systole owing to increased blood pressure and reduced aortic flow, compliance in diastole increasing as pressure declines. The arteries are stiffer with reduced compliance in hypertension. Thus, the compliance-pressure loop can provide an effective characterization of the dynamic behavior of the arterial system in terms of pressure-flow relation and blood vessel properties.

Acute Disease

The effect of age on cardiovascular risk factors in Chinese women.

Chinese women traditionally have a low incidence of coronary heart disease. However, information on cardiovascular risk factors in this population are relatively scarce. We examined these risk factors in 601 Hong Kong Chinese women (age+/-SEM, 38.5+/-0.4 years; range, 18-66 years) stratified into four age groups (group 1, < or =30 years; group 2, 31-40 years; group 3, 41-50 years; group 4, > or =51 years). Increasing age in Chinese women was associated with increased body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, fasting plasma total cholesterol, triglyceride, low-density lipoprotein, apolipoprotein B, fasting and 2-h plasma glucose, glycated haemoglobin, fasting plasma insulin and urate concentrations. After adjustment for body mass index, waist-to-hip ratio and smoking, all these age-related associations remained statistically significant except for fasting plasma insulin concentration. There was a progressive increase with age in the prevalence of glucose intolerance, hypertension, dyslipidaemia and obesity. These prevalence rates further increased in subjects aged 51 years (the mean menopausal age in Asian women) or above. These findings suggest that age had an important and independent effect on cardiovascular risk in Chinese women and that, as in Caucasians, the onset of menopause might further increase this risk.

Adolescent

Improved heterologous expression of the white-rot fungal ligninase H8 by crossover linker mutagenesis.

Using the crossover-linker mutagenesis method, the 5' noncoding region of the lambda ML-1 cDNA, which encodes the ligninase H8 isozyme of the white-rot fungus, Phanerochaete chrysosporium, was deleted with the simultaneous insertion of the putative Spodoptera frugiperda ribosome-binding sequence (RBS) (TATAAAT) directly in front of the translation-initiation codon of this gene. A recombinant baculovirus, pVL-Mu-H8, carrying the ligninase-H8 gene was successfully constructed, as determined by both sequence analysis and dot blot hybridization. A more than 18-fold increase in the expression of ligninase H8, compared to the previous pEV11-1A.3 recombinant baculovirus, was detected in the Sf-21 insect cells. This enzyme was detected within 3 d postinfection and was biologically active, capable of oxidizing the model lignin compound, veratryl alcohol. The molecular weight of the overexpressed 42 kD protein was similar to that of the native fungal ligninase-H8 isozyme and it also reacted specifically with the anti-H8 monoclonal antibody (MAb 2D4.9) in Western blot analysis.

Animals

Computer modeling of the effects of aortic valve stenosis and arterial system afterload on left ventricular hypertrophy.

The degree of left ventricular hypertrophy is generally thought to reflect the severity of aortic stenosis. However, the compounded influence of arterial system load is poorly understood. We developed a computer model to investigate the effects of aortic valve stenosis in combination with various systemic arterial parameters in the development of left ventricular hypertrophy. Data show that an increased peripheral resistance and/or aortic valve resistance, results in an increase in left ventricular wall thickness and mass, while peak systolic wall stress remains constant. Changing arterial compliance to above normal level would not induce significant changes in wall thickness, while reduction in arterial compliance below normal would cause an increase in ventricular wall thickness. When a double load is imposed on the left ventricle by way of a stenotic valve and an increased arterial afterload, a greater and an aggregated increase in wall thickness results, hastening the hypertrophic process.

Algorithms

Plasma fibrinogen concentration in a Chinese population.

Plasma fibrinogen concentration has been shown to be a predictor of major cardiovascular events. Information on plasma fibrinogen amongst Chinese has been scanty. We examined the relationships between plasma fibrinogen concentration and cardiovascular risk factors in 988 chinese subjects who underwent 75 g oral glucose tolerance test for screening for glucose intolerance. The study involved a selected sample with subjects who had an history of gestational diabetes, delivery of big babies (birth weight > or = 4 kg), equivocal plasma glucose concentrations and subjects who were family members of diabetic patients. This was mainly a non-smoking (96.6%), non-drinking (98%) and non-exercising (99%) population of which 87% (n = 855) were female. Among the 988 subjects (age +/- S.D. 36.8 +/- 10.2, range 16-79 years), plasma fibrinogen concentration ranged from 1.40 to 9.90 g/l with a mean of 3.26 +/- 0.93 g/l. On stratification of the subjects into 4 quartiles based on plasma fibrinogen concentrations, we found that increased plasma fibrinogen was associated with older age, higher body mass index (BMI), systolic and diastolic blood pressure (BP), fasting and 2 h plasma glucose (PG), prevalence of diabetes, glycated haemoglobin (HbA1c) and triglyceride (TG) level. After adjustment for age and sex, increased plasma fibrinogen concentration remained associated with higher BMI, systolic BP, 2 h PG and TG level. On multivariate analysis using age, BMI, BP, TG, HbA1c and PG as independent variables, plasma fibrinogen was independently related to plasma TG concentration and HbA1c. With 1 S.D. change in TG concentration and HbA1c, there were 3.7 and 5.2% changes in plasma fibrinogen concentration respectively. These findings emphasize the close relationships between plasma fibrinogen and cardiovascular risk factors, in particular abnormal lipid and glucose metabolism.

Adolescent

A novel biodegradable system based on gelatin nanoparticles and poly(lactic-co-glycolic acid) microspheres for protein and peptide drug delivery.

Gelatin nanoparticle-poly(lactic-co-glycolic acid) (PLGA) microsphere composites were prepared by encapsulating protein-loaded gelatin nanoparticles in PLGA microspheres. This encapsulation was conducted by using a phase separation method and a solvent extraction method. The average diameter of the gelatin nanoparticle-PLGA microsphere composites is between 160 and 175 microm. Protein loading efficiency is 93.2% for the nanoparticle-microsphere composite prepared by the phase separation method, while it is 31.31% for the composite prepared by the solvent extraction method. Protein release experiments indicate that this new composite system possesses sustained release characteristics. This system also demonstrates the capability of preventing the denaturation of protein drugs.

Biotransformation

Simple anthropometric indexes and cardiovascular risk factors in Chinese.

OBJECTIVE: Obesity is a major public health problem due to its associations with multiple cardiovascular risk factors. Although there are sophisticated methods, such as imaging, to document total body fat and its distributions, anthropometric measurements remain important in clinical practice. We examined the relationships between cardiovascular risk factors and the three commonest anthropometric measurements for obesity, body mass index (BMI), waist-hip ratio (WHR) and waist circumference (WC), in Hong Kong Chinese subjects. DESIGN AND SETTING: The data are obtained from a prevalence survey for glucose intolerance and lipid abnormality in a representative Hong Kong Chinese working population. All employees from a public utility company and a regional hospital were invited to participate. SUBJECTS: There were 1513 subjects (910 men and 603 women, mean age +/- s.e.m.: 37.5 +/- 0.2 y). All of them had no significant past medical history. MEASUREMENTS: BMI, WHR and WC of the 1513 subjects were assessed for their relationships with various cardiovascular risk factors. These include blood pressure, fasting and 2 h plasma glucose and insulin, glycated haemoglobin, total cholesterol, triglyceride, high density and low density lipoprotein cholesterol, and urine albumin concentration. RESULTS: After age adjustment, all three anthropometric indexes were significantly correlated with the major cardiovascular risk factors in both men and women. When BMI, WHR and WC were analysed according to quartiles, there was a significant trend for blood pressure, plasma triglyceride, fasting and 2 h plasma glucose and insulin to increase, and high density lipoprotein cholesterol to decrease, with increasing obesity after adjustment for age and smoking. Using stepwise regression analysis with the three indexes as independent variables, most of the variance in blood pressure, plasma lipid, insulin, glucose and urinary albumin concentration were explained either by WC or WHR. In women, BMI was the main explanatory variable for reduced high density lipoprotein cholesterol. CONCLUSIONS: In Hong Kong Chinese, BMI, WHR and WC provide important information in assessing cardiovascular risks. In men, central adiposity as reflected by WC and to some extent, WHR, explained most of the variance in blood pressure, plasma glucose, lipid, insulin and albuminuria. In women, all three indexes reflecting general and central obesity contribute to the variance in these risk factors.

Adult

Vessel growth and collapsible pressure-area relationship.

The role that the pattern of vessel wall growth plays in determining pressure-lumen area (P-A) and pressure-compliance curves was examined. A P-A vessel model was developed that encompasses the complete range of pressure, including negative values, and accounts for size given the fixed length, nonlinear elastic wall properties, constant wall area, and collapse. Data were obtained from excised canine carotid and femoral arteries, jugular veins, and elastic tubing. The mean error of estimate was 8 mmHg for all vessels studied and 2 mmHg for blood vessels. The P-A model was employed to examine two patterns of arterial wall thickening, outward growth and remodeling (constant wall area), under the assumption of constant wall properties. The model predicted that only outward wall growth resets compliance such that it increases at a given arterial pressure, explaining previously contradictory data. In addition, it was found that outward wall growth increases the lumen area between normal and high pressures. Remodeling resulted in lumen narrowing and a decrease in compliance for positive pressures.

Animals

Clozapine: a mimicry of phaeochromocytoma.

OBJECTIVE: To report a case of clozapine-induced hypertension with raised urinary catecholamines. CLINICAL PICTURE: A 27-year-old man fulfilling DSM-III-R criteria for catatonic schizophrenia was treated with clozapine. He later developed both hypertension and raised urinary catecholamines which mimicked phaeochromocytoma. TREATMENT: Clozapine was withdrawn. OUTCOME: Both blood pressure and urinary catecholamines normalised. CONCLUSIONS: Clozapine may induce sympathetic hyperactivity.

Adult

Topography and immunogenicity of bluetongue virus VP7 epitopes.

The core of bluetongue virus (BTV) consists of ten dsRNA viral genome segments and five proteins, including two major (VP7 and VP3) and three minor (VP1, VP4 and VP6) components. The major core protein VP7 is believed to be an important structural constituent because it interacts, not only with the underlying core protein VP3, but also with two outer capsid proteins (VP2 and VP5). In this communication we summarise data on the mapping of at least six different epitopes of VP7 distributed along the molecule. Two of the six epitopes have not been mapped previously. The accessibility of these epitopes in intact virions and core particles was analysed using immunoelectron microscopy. The epitope located near the N-terminus of VP7 was accessible at the surface of intact virions and core particles. Epitopes in other parts of the VP7 molecule were detected weakly in core particles but not in intact virions. These results support the proposal that VP7 molecules are orientated with their N-terminus accessible on the surface of either the particle or at least one of the three different channels observed by cryoelectron microscopy in the outer capsid layer. Analysis of the immune response to BTV-infected or -immunised sheep and rabbits to three selected epitopes, which are located in different regions of the VP7 molecule, demonstrated that all of them were recognised by the animals tested. These results provided further molecular evidence suggesting that VP7 is indeed a major immunogenic antigen ideal for BTV antibody detection.

Animals

Analysis of effect of two concurrent ischaemic zones on left ventricular function.

Left ventricular (LV) function due to two concurrent ischaemic zones (IZs) is investigated using a cardiovascular system model. The model comprises a three-compartment LV, the venous return and the arterial system. Haemodynamic responses of the LV to changes in the IZ size and myocardial contraction timings are explored. Results show that the greater the degree of asynschonisation is between the normal zone and the IZ, and the larger the ischaemic size, the more severe the LV dysfunction. Pre-load augmentation improves LV function. Model-predicted features are consistent with reported observations associated with myocardial ischaemia. The extent of the usefulness and limitations of this model is also discussed.

Computer Simulation

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

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

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

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