Biomedical subjects

J C Lai

Publications and source records attributed to J C Lai.

At least 37 records · Page 2Linked to original sources

PubMed1997

Unemployment and psychological health among Hong Kong Chinese women.

The impact of unemployment on psychological health, indexed by the General Health Questionnaire, was studied in 86 unemployed and 79 employed Chinese women in Hong Kong. As with findings reported in the West, the present results showed that the unemployed participants were more disturbed than their steadily employed peers. In addition, the prevalence rate of disturbance (54%) observed in the present sample of unemployed women is comparatively higher than those of Western samples reported previously. Implications of these preliminary findings for research on psychological aspects of unemployment among Hong Kong Chinese were discussed.

Adult↗

PubMed1996

IL-12 inhibits endotoxin-induced inflammation in the eye.

Interleukin-12 (IL-12) is a heterodimeric cytokine that induces interferon (IFN)-gamma production and an increased generation of Th1 cells. Both IL-12 and IL-12 antagonists are being studied for the treatment of allergic reactions, autoimmune disease and malignancy. The goal of the present experiments was to examine the importance of IL-12 in endotoxin-induced ocular inflammation. The number of inflammatory cells infiltrating eyes with endotoxin-induced uveitis (EIU) was significantly increased in animals treated with intraperitoneal anti-IL-12 antibody when compared to control animals, but there was no difference in infiltrating inflammatory cells in the eyes of animals treated with IL-12 when compared to controls. In contrast, intraocular injection of IL-12 significantly inhibited the development of endotoxin-induced intraocular inflammation. The infiltrating inflammatory cells were reduced in the eyes of animals receiving intraocular IL-12 when compared to controls. Cytokine analysis of the aqueous humor obtained from eyes with EIU showed increased levels of IFN-gamma and decreased levels of IL-6 in eyes receiving intraocular IL-12. These data show that IL-12 has an inhibitory effect on endotoxin-induced inflammation in the eye and suggest that IL-12 can have an immunoregulatory function in some forms of inflammatory disease.

Animals↗

PubMed1996

Reduced susceptibility to IL-1 and endotoxin in transgenic mice expressing IL-1 in their lens.

To learn about the effects of chronic exposure to IL-1 we generated a transgenic (Tg) mouse line that expresses human IL-1 beta under the control of the lens alpha-A crystallin promoter. Expression of human IL-1 beta was restricted to the eye; neither the protein nor its mRNA were detected in various other organs of the Tg mice. The Tg mice develop severe ocular inflammation shortly after birth, which affects the lens and other eye tissues and apparently allows the release of IL-1 into the circulation. Here we report that the Tg mice exhibit decreased responsiveness to IL-1 and lipopolysaccharide (LPS), as compared to their wild-type littermate controls: (1) when injected with IL-1 the Tg mice produced lower levels of serum amyloid A than their controls; (2) thymocytes of the Tg mice responded less vigorously in culture to stimulation with IL-1; and (3) Tg mice showed lower morbidity and mortality than their controls when injected with toxic amounts of LPS. These data suggest that chronic exposure to IL-1 in the Tg mice induces partial resistance to this cytokine, analogous to the reduced responsiveness to IL-1 in animals pretreated with this proinflammatory cytokine.

Animals↗

PubMed1996

The 13C isotope and nuclear magnetic resonance: unique tools for the study of brain metabolism.

As studies of brain metabolism grow in complexity, investigators turn increasingly to nuclear magnetic resonance spectroscopy combined with 13C isotopic labeling. The unique ability to detect labeling non-destructively in specific carbon positions of individual compounds has opened the way to investigate brain metabolism in systems ranging from cellular preparations to the human brain in vivo. This review is written for investigators whose backgrounds do not include detailed knowledge of principles of nuclear magnetic resonance. Its purpose is to show the wide array of NMR techniques for 13C detection that are available for application in different systems to study aspects of brain metabolism, such as metabolic compartmentation and measurements of the tricarboxylic acid cycle rate in vivo. Basic NMR concepts are explained, and, because each detection method possesses specific advantages to address the requirements of different experimental goals, basic explanations and examples are given for each technique. The review should provide readers with a basic understanding of the methods of 13C detection by NMR and assess which of the methods are most applicable to the particular issues they may face in their own research.

Brain↗

PubMed1996

Dispositional optimism and coping with academic examinations.

Correlations between scores on dispositional optimism and four categories of coping strategies for academic examinations for a group of 248 Hong Kong undergraduates were .25 for Self-encouragement and -.20 for Cognitive Avoidance. These results lend partial support to the association of adaptive coping and optimism, measured by the Life Orientation Test.

Achievement↗

PubMed1995

In vitro oxidation of vitamin E, vitamin C, thiols and cholesterol in rat brain mitochondria incubated with free radicals.

The kinetics of oxidation of endogenous antioxidants such as vitamins C and E and thiols as well as membrane cholesterol in isolated rat brain mitochondria were studied. Oxidation was induced by incubating the mitochondria at 37 degrees C with the free radical generators 2,2' azobis (2'-amidinopropane) dihydrochloride (ABAPH) and 2,2' azobis (2,4-dimethyl) valeronitrile (ABDVN) which undergo thermal decomposition to yield free radicals. An approximate order for the in vitro ease of oxidation was: ascorbate >> alpha-tocopherol > sulfhydryls >> cholesterol. However, small amounts of ascorbate were present in the mitochondria when alpha-tocopherol and sulfhydryl compounds were getting oxidized. This observation is different from those with more homogeneous biological substrates like blood plasma or serum. The order of oxidation of the various compounds is a function of not only the redox potentials but also the (a) concentrations of the oxidized and reduced species, (b) compartmentation of the compounds and (c) enzymatic and nonenzymatic systems for the repair or regeneration of the individual antioxidants. Even though ascorbate levels are quite low within mitochondria this nutrient may play a major role as a first line of defense against oxidative stress. The lipid-soluble ABDVN was much more potent in oxidizing membrane alpha-tocopherol and thiols than the water-soluble ABAPH. With both free radical generators the rate of oxidation of the antioxidants consisted of two phases. The initial phase, that is more rapid, may represent a pool of antioxidant that is involved in immediate antioxidant protection of the organelle with the slower compartment being responsible for replenishing the faster pool whenever needed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines↗

PubMed1995

The moderating effect of optimism on the relation between hassles and somatic complaints.

The relations between hassles, dispositional optimism, and prospective reports of physical symptoms were examined in a group of 90 Hong Kong undergraduates. Given that most hassle scales are confounded by physical and psychological symptomatology, a decontaminated scale specifically tailored to the experiences of college students was used. Multiple regression analyses indicated that hassle scores and the interaction of hassles and optimism uniquely and reliably predicted symptom reporting. Optimism, however, did not reliably predict symptom reports when effects of hassles and the interaction of hassles and optimism were controlled. Inspection of the interaction showed that optimism predicted symptom scores only at high levels of hassles. The underlying mechanisms were discussed in the light of previous data linking optimism and adaptational outcomes via coping. It was suggested that further pursuit of the connection between optimism and coping in relation to measures of life stress would be worthwhile.

Adaptation, Psychological↗

PubMed1994

Heterogeneity of monoamine oxidase activities in synaptic and non-synaptic mitochondria derived from three brain regions: some functional implications.

The heterogeneity of monoamine oxidase (MAO; EC 1.4.3.4) activities was studied in two fractions of synaptic mitochondria (SM & SM2) and one fraction of non-synaptic ("free") mitochondria (M) isolated from three rat brain regions (cerebral cortex, striatum, and pons & medulla) by the Lai and Clark (1979, 1989) method in order to elucidate the heterogeneity of MAO at the subcellular and brain regional levels. The activities toward serotonin (MAO-A), benzylamine (MAO-B), and dopamine (MAO-DA) in SM2 from all three regions were different from the corresponding values in SM. In addition, the various MAO activities in SM and SM2 showed heterogeneous distribution with respect to the three brain regions investigated. Both the distribution of MAO-A and MAO-B in non-synaptic mitochondria (M) did not show marked regional differences although MAO-DA in M varied depending on the region. These results clearly demonstrate that the distribution of MAO activities toward different substrates is heterogeneous both at the subcellular and the brain regional levels. The MAO-A:MAO-B ratios in the various mitochondrial fractions also showed trends that are consistent with this hypothesis. Furthermore, in fraction SM of synaptic mitochondria, this ratio was consistently higher than values in the other two mitochondrial fractions (SM2 & M) irrespective of the region from which they were isolated. In view of the functional importance of MAO in the regulation and compartmentation of amine metabolism, the heterogeneity of MAO at subcellular and regional levels may assume pathophysiological importance in neurological diseases (e.g., Parkinsonism) with which altered amine metabolism is associated.

Animals↗

PubMed1994

Brain mitochondrial citrate synthase and glutamate dehydrogenase: differential inhibition by fatty acyl coenzyme A derivatives.

Organic acidemia is found in several metabolic encephalopathies (e.g., hepatic and valproate encephalopathies, Reye's syndrome, and hereditary organic acidemias). Although fatty acids are known to be neurotoxic, the underlying mechanisms have not been fully elucidated. It has been hypothesized that one mechanism underlying fatty acid neurotoxicity is the selective inhibition of rate-limiting and/or regulated tricarboxylic acid (TCA) cycle and related enzymes by fatty acyl-coenzyme A (CoA) derivatives. To test the hypothesis, this study has examined the effects of several fatty acyl-CoAs on citrate synthase (CS) and glutamate dehydrogenase (GDH) in brain mitochondria. At levels higher than 100 microM, butyryl-CoA (BCoA; a short-chain acyl-CoA; IC50 approximately 640 microM), octanoyl-CoA (OCoA; a medium-chain acyl-CoA; IC50 approximately 380 microM), n-decanoyl-CoA (DCoA; a medium-chain acyl-CoA; IC50 approximately 436 microM), and palmitoyl-CoA (PCoA; a long-chain acyl-CoA; IC50 approximately 340 microM) inhibited brain mitochondrial CS activity in a concentration-related manner. However, these fatty acyl-CoAs were less effective inhibitors (IC50 values for OCoA, DCoA, and PCoA being approximately 1260, 420, and 720 microM, respectively) of brain mitochondrial GDH activity. Compared to the other three acyl-CoAs investigated, BCoA was a very poor inhibitor of GDH. These results demonstrate that fatty acyl-CoAs are inhibitors of brain mitochondrial CS and GDH activities only at pathological/toxicological levels. Thus, the fatty acyl-CoA inhibition of brain mitochondrial CS and GDH is unlikely to assume major pathophysiological and/or pathogenetic importance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyl Coenzyme A↗

PubMed1994

FT-IR measurement of mercaptoundecahydrododecaborate in human plasma.

A simple and rapid method for the quantitative measurement of mercaptoundecahydrododecarborate (BSH), (which presently is one of the most useful agents for Boron Neutron Capture Therapy) in human plasma was developed by using Fourier transform infrared spectroscopy. Different spacer thicknesses of the liquid sampling cell were examined and the optimal results were obtained by the 0.05 mm spacer. The subtraction of water absorbance from sample spectra resolved a B-H band at 2493 cm-1. The quantitative measurement of BSH was carried out by integration of the B-H band in the wavenumber range of 2534-2440 cm-1. However, at the lower BSH concentration range, a visual inspection of the spectrum to determine the wavenumber range was necessary so as to avoid any negative areas to be integrated. The lower limit of detection of BSH in aqueous solution and human plasma was 5 micrograms ml-1 (about 2.5 ppm of boron).

Borohydrides↗

PubMed1994

Differential predictive power of the positively versus the negatively worded items of the Life Orientation Test.

A self-report measure of dispositional optimism, the Life Orientation Test, was administered to a group of 202 Hong Kong undergraduates. Consistent with prior findings, factor analysis yielded a two-factor solution with all positively worded items loaded on the first factor and all the negatively worded items loaded on the second. Prediction of physical symptom reports from scores on the two subscales was then tested with 85 subjects randomly selected from the original sample. Only the complete test and the subscale defined by the positively phrased items predicted symptom levels concurrently as well as prospectively over 3 wk. The negative subscale suggested by previous research as tapping pessimism rather than dispositional optimism showed no significant correlation with symptom levels. Moreover, when scores of the positive rather than the negative subscale were controlled, the significant correlation between scores on the Life Orientation Test and symptom reports was eliminated. These findings suggested a multidimensional view of the test and that the positive subscale may be sufficient to measure optimism validly. Implications of these for the personality dimensions of positive versus negative affectivity are also discussed.

Adult↗

PubMed1993

Brain regional distributions of monoamine oxidase activities in postnatal development in normal and chronically manganese-treated rats.

To investigate the hypothesis that manganese toxicity may affect the development of the monoamine oxidases (MAOs) in brain, the regional distributions of the A (serotonin-oxidizing) and B (benzylamine-oxidizing) forms of MAO were determined in manganese-treated (1 mg or 10 mg of MnCl2.4H2O per ml of drinking water from conception onwards until the rats were used for experiments) and untreated male rats during various stages of postnatal development. The age-related variations in regional MAO-A activities (especially in pons and medulla and in cerebellum) were more marked than those in regional MAO-B activities. The MAO-A:MAO-B activity ratios decreased in all regions during development. Chronic manganese treatment (at the specified doses) did not significantly alter the age-related changes in regional MAO-A and MAO-B activities; nor were the A:B activity ratios affected. The results suggest that there is differential expression of MAO isoforms in various brain regions during postnatal development but the expression is not affected by chronic manganese toxicity.

Aging↗

PubMed1993

High activities of glutamine transaminase K (dichlorovinylcysteine beta-lyase) and omega-amidase in the choroid plexus of rat brain.

Certain halogenated hydrocarbons, e.g., dichloroacetylene, are nephrotoxic to experimental animals and neurotoxic to humans; cysteine-S-conjugate beta-lyases may play a role in the nephrotoxicity. We now show that with dichlorovinylcysteine as substrate the only detectable cysteine-S-conjugate beta-lyase in rat brain homogenates is identical to glutamine transaminase K. The predominant (mitochondrial) form of glutamine transaminase K in rat brain was shown to be immunologically distinct from the predominant (cytosolic) form of the enzyme in rat kidney. Glutamine transaminase K and omega-amidase (constituents of the glutaminase II pathway) activities were shown to be widespread throughout the rat brain. However, the highest specific activities of these enzymes were found in the choroid plexus. The high activity of glutamine transaminase K in choroid plexus was also demonstrated by means of an immunohistochemical staining procedure. Glutamine transaminase K has a broad specificity toward amino acid and alpha-keto acid substrates. The omega-amidase also has a broad specificity; presumably, however, the natural substrates are alpha-ketoglutaramate and alpha-ketosuccinamate, the alpha-keto acid analogues of glutamine and asparagine, respectively. The high activities of both glutamine transaminase K and omega-amidase in the choroid plexus suggest that the two enzymes are linked metabolically and perhaps are coordinately expressed in that organ. The data suggest that the natural substrate of glutamine transaminase K in rat brain is indeed glutamine and that the metabolism of glutamine through the glutaminase II pathway (i.e., L-glutamine and alpha-keto acid-->alpha-ketoglutarate and L-amino acid + ammonia) is an important function of the choroid plexus. Moreover, the present findings also suggest that any explanation of the neurotoxicity of halogenated xenobiotics must take into account the role of glutamine transminase K and its presence in the choroid plexus.

Amidohydrolases↗

PubMed1993

Glycolysis-citric acid cycle interrelation: a new approach and some insights in cellular and subcellular compartmentation.

In the development of an integrated approach to study metabolic compartmentation and regulation in brain, we have emphasized the importance, versatility, and need to exploit the recent methodological advances in (1) NMR spectroscopy, (2) primary cultures of neurons and glial cells, and (3) subcellular fractionation (especially brain mitochondrial isolation). The integrated approach has the advantage of being able to draw data and inferences based on some combination of results derived from in vivo, cellular, and subcellular studies. For example, some in vivo NMR data may suggest that an enzymatic step may be rate-limiting in a particular pathway. This information may be used to frame testable hypotheses and questions that can be investigated in experiments involving primary cultures of neural cells and subcellular fractions. Subsequently, the data from such in vitro studies could serve as the bases for constructing the hypothetical framework for predicting the regulatory role, in vivo, of the enzyme in the pathway. We have discussed the known as well as the as yet ill-defined facets of the cellular and subcellular aspects of the glycolysis-citric acid cycle interrelation and have attempted to illustrate how such an integrated approach could be applied to generate testable hypotheses for investigating the mechanisms concerned with metabolic compartmentation and regulation in brain. In the process of the illustration, we discuss some of the evidence in support of the general hypothesis that the transfer of reducing equivalents across the inner mitochondrial membrane plays a major role in mediating the coupling of the glycolytic flux to that of the citric acid cycle. We have given some indications as to how this hypothesis could be further investigated employing our approach. Moreover, we hope that other workers will find this integrated approach useful in designing multidisciplinary studies to investigate mechanistic issues related to this important theme.

Animals↗

PubMed1993

Differential effects of fatty acyl coenzyme A derivatives on citrate synthase and glutamate dehydrogenase.

We investigated the hypothesis that one mechanism underlying fatty acid toxicity is the selective inhibition of rate-limiting and/or regulated tricarboxylic acid cycle and related enzymes by fatty acyl coenzyme A (CoA) derivatives by examining the effects of several fatty acyl CoAs on purified citrate synthase (CS) and glutamate dehydrogenase (GDH). The results indicate that, at pathophysiological levels, palmitoyl CoA, a long-chain acyl CoA, is a potent inhibitor of CS and GDH with IC50 values of 3-15 microM. At much higher levels (in the pathological and toxicological range), octanoyl and decanoyl CoA (medium-chain acyl CoAs) inhibited both enzymes with IC50 values of 0.4-1.6 mM. Butyryl CoA, a short-chain acyl CoA, inhibited CS (IC50 = 0.9 mM) at toxicological levels but inhibited GDH poorly. These results suggest that the long-chain fatty acyl CoA inhibition of CS and GDH may assume some pathophysiological importance in fatty acid toxicity and in metabolic encephalopathies in which organic acidemia is persistent. The findings also provide additional support for the original hypothesis.

Acyl Coenzyme A↗

PubMed1992

Neurochemical changes in rats chronically treated with a high concentration of manganese chloride.

Several neurochemical parameters were studied in brain regions of rats chronically treated with a high concentration of manganese chloride (20 mg MnCl2.4H2O per ml. of drinking water) throughout development until adulthood. Large increases in Mn accumulation were found in all brain regions (hypothalamus, +530%; striatum, +479%; other regions, +152 to +250%) of Mn-treated adult rats. In these animals, Ca levels were decreased (-20 to -46%) in cerebellum, hypothalamus, and cerebral cortex but were increased (+186%) in midbrain. Mg levels were decreased (-12 to -32%) in pons and medulla, midbrain, and cerebellum. Fe levels were increased (+95%) in striatum but were decreased (-28%) in cerebral cortex. Cu levels were increased (+43 to +100%) in pons and medulla and striatum but Zn levels were decreased (-30%) in pons and medulla. Na levels were increased (+22%) in striatum but those of K and Cl remained unchanged. Type A monoamine oxidase activities were decreased (-13 to -16%) in midbrain, striatum, and cerebral cortex, but type B monoamine oxidase activities decreased (-13%) only in hypothalamus. Acetylcholinesterase activities were increased (+20 to +22%) in striatum and cerebellum. The results are consistent with our hypothesis that chronic manganese encephalopathy not only affects brain metabolism of Mn but also that of other metals.

Acetylcholinesterase↗

PubMed1992

Differential effects of metal ions on type A and type B monoamine oxidase activities in rat brain and liver mitochondria.

To investigate the hypothesis that neurotoxic metals can exert their toxicity through the direct inhibition of monoamine oxidases (MAOs), the effects of several neurotoxic metal ions on type A (MAO-A) and type B (MAO-B) monoamine oxidase activities in rat forebrain nonsynaptic mitochondria and rat liver mitochondria were studied. At pathophysiological levels (10-100 microM), Cu2+ and Cd2+ are good inhibitors of brain mitochondrial MAO-A and, to a lesser extent, liver mitochondrial MAO-A. The inhibition of MAO-B activities in brain and liver mitochondria by Cu2+ and Cd2+ is only detected at the higher end of the concentration range (i.e., 50-100 microM). At the pathophysiological level of 0.5 mM, Al3+ only inhibits brain mitochondrial MAO-A but at the higher level of 2.5 mM, it inhibits both forms of MAO in brain as well as liver mitochondria. Even at toxic levels (e.g., 5 mM), neither Mn2+ nor Li+ inhibits the activities of MAO-A and MAO-B in brain and liver mitochondria. Our results are consistent with the hypothesis that some neurotoxic metals can exert their toxicity through the direct inhibition of the isoforms of MAO. Our data also suggest that the selective inhibition of brain MAO-A by Cu2+ and Cd2+ may assume pathophysiological importance in the neurotoxicity of copper and cadmium.

Animals↗

PubMed1992

Changes in brain regional manganese and magnesium levels during postnatal development: modulations by chronic manganese administration.

Manganese (Mn) and magnesium (Mg) levels in hypothalamus, cerebellum, pons and medulla, striatum, midbrain, and cerebral cortex of control and Mn-treated (10 mg MnCl2.4H2O per ml of drinking water) rats during postnatal development were studied using instrumental neutron activation analysis. The age-dependent Mn accumulation showed regional variation: at day 5, this accumulation was most marked in striatum (12.05 micrograms/g wet weight) but least marked in cerebral cortex (0.85 micrograms/g wet weight). By day 10, pons and medulla, and hypothalamus were regions with, respectively, the highest (4.73 micrograms/g wet weight) and the lowest (0.52 micrograms/g wet weight) Mn levels. By contrast, brain regional Mn variations were less pronounced in weanling and adult rats. The age-dependent Mg accumulation showed regional variation at day 5, being most marked in pons and medulla (720 micrograms/g wet weight) and least marked in cerebral cortex (295 micrograms/g wet weight). Mg levels in all regions decreased after day 5; by day 120, only Mg level in cerebral cortex was lower than levels in other regions (the latter being very similar). In general, the age-related decreases in Mn and Mg levels paralleled the decreases in water content and increases in tissue weight, suggesting that the maturation of the blood-brain barrier may play important role(s) in brain Mn and Mg homeostasis. Chronic Mn-treatment from conception onwards altered the regional Mn and Mg distribution patterns during development. Our results are consistent with the hypothesis that chronic Mn toxicity exerts modulatory effects on brain regional metabolism and homeostasis of Mn and other metals during development.

Aging↗