Search PubMed⌕ Search

Biomedical subjects

J K Li

Publications and source records attributed to J K Li.

At least 37 records · Page 2Linked to original sources
PubMed1998

Poly(vinyl alcohol) nanoparticles prepared by freezing-thawing process for protein/peptide drug delivery.

Poly(vinyl alcohol) (PVA) hydrogel nanoparticles have been prepared by using a water-in-oil emulsion technology plus cyclic freezing-thawing process. The PVA hydrogel nanoparticles prepared by this method are suitable for protein/peptide drug delivery since formation of the hydrogel does not require crosslinking agents or other adjuvants and does not involve any residual monomer. Particularly, there is no emulsifier involved in this new method. Bovine serum albumin (BSA), as a model protein drug, is incorporated into the PVA hydrogel nanoparticles. The PVA hydrogel nanoparticles possess a skewed or log-normal size distribution. The average diameter of the PVA hydrogel nanoparticles is 675.5+/-42.7 nm. Protein drug loading efficiency in the PVA hydrogel nanoparticles is 96.2+/-3.8%. The PVA hydrogel nanoparticles swell in an aqueous solution and the swelling degree increases with the increase of temperature. In vitro release studies show that the BSA release from the nanoparticles can be prolonged to 30 h. The BSA release follows a diffusion-controlled mechanism. The number of freezing-thawing cycle and release temperature both influence BSA release rate considerably. Less freezing-thawing cycle or higher release temperature leads to faster drug release. The BSA is stable during preparation of the PVA hydrogel nanoparticles.

Chemical Phenomena↗
PubMed1998

Glycated haemoglobin and cardiovascular risk factors in Chinese subjects with normal glucose tolerance.

Increased plasma glucose concentration is a predictive factor for mortality in both diabetic and non-diabetic subjects. Although glycated haemoglobin (HbA1c) is a useful index of mean blood glucose concentrations over the preceding 1 to 3 months, there are few data regarding its relationship to cardiovascular risk. We have examined the relationship between HbA1c and cardiovascular risk factors in 1280 subjects with normal glucose tolerance. Based on HbA1c tertiles (tertile 1: n = 427, 262 men and 165 women, HbA1c level: 2.9-4.7% in men and 3.2-4.2% in women; tertile 2: n = 426, 261 men and 165 women, HbA1c level: 4.7-5.1% in men and 4.2-4.6% in women; tertile 3: n = 427, 262 men and 165 women, HbA1c level: 5.1-6.7% in men and 4.6-6.9% in women), increasing HbA1c was associated with increasing age, blood pressure, waist-hip ratio, fasting and 2-h plasma glucose, 2-h insulin, cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and urate concentrations. When age and sex were included as covariates, increasing HbA1c remained associated with increasing fasting and 2-h plasma glucose, 2-h insulin, total cholesterol, and low-density lipoprotein cholesterol concentrations. These findings emphasize the importance of hyperglycaemia, as reflected by HbA1c, as a continuum in the evaluation of cardiovascular risk. Furthermore, these findings support the hypothesis that cardiovascular disease risk commences with rising glucose concentrations before 'conventionally-defined' glucose intolerance occurs.

Adult↗
PubMed1998

Beta-adrenergic stimulation of reperfused myocardium after 2-hour ischemia.

Postischemic myocardium possesses considerable contractile and metabolic reserves, but their mobilization could result in increased cell death. We tested the hypothesis that beta-adrenergic stimulation of reperfused myocardium would increase segment work more than O2 consumption, thereby improving efficiency without increased cell death. In 16 open-chest anesthetized dogs, the left anterior descending coronary artery (LAD) was ligated for 2 h; during the reperfusion period, isoproterenol (ISO; 0.1 microg/kg/min, i.v.) was administered to nine of the animals. Regional myocardial segment length and force were measured in the anterior (LAD) and posterior circumflex coronary artery (CFX) regions of the left ventricular myocardium. Work was calculated as the integrated products of force and shortening for each region. Regional myocardial O2 consumption was obtained from LAD flow and arterial and local venous O2 saturations. Infarct size (tetrazolium) was measured in the treated and untreated hearts at the end of the experiment. In untreated hearts, the first derivative of left ventricular pressure, cardiac output, and external work were significantly depressed during reperfusion; ISO restored all values to preocclusion levels. Regional myocardial work in both LAD and CFX regions was significantly increased by ISO (from 564 +/- 207 to 1,635 +/- 543 g/mm/min in LAD, and from 753 +/- 90 to 1,426 +/- 245 g/mm/min in CFX). Efficiency (work/oxygen consumption) of the reperfused region was similarly increased. LAD flow was significantly increased by ISO, and O2 extraction was unchanged. Infarct size was 28.2 +/- 4.7% in untreated hearts and 29.0 +/- 3.5% in ISO hearts. Thus isoproterenol stimulation significantly improved both regional and global function without subsequent evidence of increased cell death.

Adrenergic beta-Agonists↗
PubMed1998

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↗
PubMed1998

Antibodies to glutamic acid decarboxylase in young Chinese diabetic patients.

Antibodies to glutamic acid decarboxylase (GAD) are a useful autoimmune marker for type 1 diabetes mellitus in Caucasians. We examined antibodies to GAD and their relationships with clinical features and pancreatic beta cell function in 140 young Chinese diabetic patients. Over an 18-month period beginning in 1995, 140 young Chinese diabetic subjects with age of onset of disease < or = 35 years and age < 40 years were recruited consecutively, irrespective of their modes of presentation. Clinical features, antibodies to GAD and pancreatic beta cell function (using a glucagon stimulation test) were examined. Increased levels of antibodies to GAD (> 18 units) were detected in 12.1% (n = 17) of these subjects. Forty-three (31%) patients had a classical type 1 presentation and 65 (46%) patients were insulin-deficient based on post-glucagon plasma C-peptide levels. Patients who were insulin-deficient and had a type 1 presentation had the highest prevalence of antibodies to GAD (29.0%) compared with patients who had a type 2 presentation and were non-insulin deficient (6.4%, P = 0.003). Patients who had antibodies to GAD had lower body mass index and waist-hip ratio, earlier onset of disease, lower blood pressure, plasma triglyceride and C-peptide, and higher concentrations of plasma high-density lipoprotein cholesterol and glycated haemoglobin, and were more likely to require drug treatment, compared with those without antibodies to GAD. In conclusion, there was a low prevalence of antibodies to GAD in Chinese young diabetic patients although such antibodies remained a relatively specific marker for insulin deficiency and acute presentation. Causes other than autoimmunity should be sought to explain the high prevalence of insulin deficiency in these young Chinese patients.

Antibodies↗
PubMed1998

Combined use of a fasting plasma glucose concentration and HbA1c or fructosamine predicts the likelihood of having diabetes in high-risk subjects.

OBJECTIVE: To assess the validity of using fasting plasma glucose (FPG) concentrations in conjunction with HbA1c or fructosamine for the screening of diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS: In this study 2,877 Hong Kong Chinese (565 [19.6%] men; 2,312 [80.4%] women) with various risk factors for glucose intolerance underwent a 75-g oral glucose tolerance test (OGTT) for screening of diabetes. The risk factors included a family history positive for diabetes, a history of gestational diabetes or impaired glucose tolerance, and obesity. RESULTS: Using World Health Organization (WHO) criteria, 1,593 (55.4%) had normal glucose tolerance, 657 (22.8%) had impaired glucose tolerance, and 627 (21.8%) had diabetes. When the 1997 American Diabetes Association (ADA) criteria were applied, 394 (13.7%) had diabetes with an FPG > or = 7.0 mmol/l. Using multiple receiver operating characteristic curve analysis, the paired values of an FPG of 5.6 mmol/l and a HbA1c of 5.5% gave an optimal sensitivity of 83.8% and specificity of 83.6% to predict a 2-h plasma glucose (PG) > or = 11.1 mmol/l. Likewise, the paired values of an FPG of 5.4 mmol/l and a fructosamine level of 235 mumol/l (n = 2,408) gave an optimal sensitivity of 81.5% and specificity of 83.2%. An FPG > or = 5.6 mmol/l and an HbA1c > or = 5.5% was 5.4-fold more likely to occur in diabetic subjects (based on the WHO criteria) compared with nondiabetic subjects. For paired parameters less than these values, the likelihood ratio of this occurring in diabetic subjects was only 0.11. Similarly, an FPG > or = 5.4 mmol/l and a fructosamine > or = 235 mumol/l was fivefold more likely to occur in diabetic subjects than in nondiabetic subjects, with both parameters less than these values having a likelihood ratio of 0.04. Using these paired values as initial screening tests, only subjects who had an FPG > or = 5.6 mmol/l and < 7.8 mmol/l and an HbA1c > or = 5.5% (n = 642) required an OGTT to confirm diabetes, thereby saving 77.7% [(2,877-642)/2,877] of the OGTTs performed. Similarly, only subjects who had an FPG > or = 5.4 mmol/l and < 7.8 mmol/l and a fructosamine > or = 235 mumol/l (n = 526) required OGTT to confirm diabetes, meaning that 78.2% [(2,408-526)/2,408] of the OGTTs could have been saved. Based on the 1997 ADA criterion of an FPG cutoff value of 7.0 mmol/l, the corresponding numbers of OGTTs to be saved were 82.6% and 85.5%, respectively. CONCLUSIONS: The paired values of FPG and HbA1c or FPG and fructosamine helped to identify potentially diabetic subjects, the diagnosis of which could be further confirmed by the 75-g OGTT. Using this approach approximately 80% of OGTTs could have been saved, depending on the diagnostic cutoff value of FPG.

Adult↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗