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Biomedical subjects

J C Lai

Publications and source records attributed to J C Lai.

At least 19 recordsLinked to original sources
PubMed2001

Alternations in quantities and activities of erythrocyte cytosolic carbonic anhydrase isoenzymes in glucose-6-phosphate dehydrogenase-deficient individuals.

BACKGROUND: This study was designed to evaluate the quantitative and activity alterations of cytosolic carbonic anhydrase (CA) isoenzymes in the erythrocytes of glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. METHODS: Western Blot and CA esterase activity analysis were employed to measure cytosolic erythrocyte CA isoenzymes. RESULTS: The total CA activities were analyzed from erythrocytes of 30 healthy and 30 G6PD-deficient individuals. The mean values with standard error (SE) were 22.9+/-1.69 U/gHb and 27.2+/-2.1 U/gHb (P<0.01), respectively. The ratio of CAI/CAII of G6PD-deficient individuals (1.28+/-0.06) was significantly lower than that of the normal subjects (3.79+/-0.18) (P<0.001). Furthermore, the concentration of CAIII in G6PD-deficient individuals was significantly lower than that of the normal subjects (P<0.001) and there were significant correlations between the concentration of CAI, CAII, CAIII, and ratio of CAI/CAII, and the activity concentration of G6PD. CONCLUSIONS: Different carbonic anhydrase isoenzymes may serve different roles in the G6PD-deficient erythrocyte. CAI could be used as an indicator for hemolytic anemia. CAII is able to compensate for the functions of CAI and increased expression of CAII will promote oxidative damage. CAIII can provide the G6PD-deficient persons with some extent of protection against oxidative damage.

Adult↗
PubMed2001

Traumatic hyphema in children: risk factors for complications.

OBJECTIVE: To identify risk factors associated with higher rates of ocular complications in children with traumatic hyphema. METHODS: Consecutive inpatient records from July 1990 through December 1997 were retrospectively reviewed for all children (aged < or = 18 years) who were admitted to the Wilmer Ophthalmological Institute, Baltimore, Md, within 48 hours of a closed-globe injury leading to hyphema. Data obtained included age, sex, race, sickle cell status, initial and final visual acuities, hyphema size and intraocular pressure at presentation, the occurrence of a secondary hemorrhage, subsequent intraocular pressure elevations, and therapeutic interventions. RESULTS: Forty children fulfilled the inclusion criteria: 20 African American, 1 Asian American, and 19 white. Five of the 20 African American children had sickle cell trait, and 1 had sickle cell anemia. The rate of secondary hemorrhage was statistically higher in the African American population (P =.05), but no statistical difference existed between the rate of secondary hemorrhage in patients with and without sickle cell hemoglobinopathy. Sickle cell hemoglobinopathy was associated with a higher intraocular pressure at presentation (P =.03) and during inpatient follow-up (P =.02). CONCLUSIONS: In the setting of traumatic hyphema, African American children appear to be at greater risk for developing a secondary hemorrhage. In our patients, sickle cell hemoglobinopathy increased the risk of intraocular pressure elevation, but did not seem to increase the risk of rebleeding beyond that associated with race. Larger studies are needed to validate these observations.

Adolescent↗
PubMed2000

Brain regional development of the activity of alpha-ketoglutarate dehydrogenase complex in the rat.

This study was initiated to test the hypothesis that the development of alpha-ketoglutarate dehydrogenase complex (KGDHC) activity, like that of pyruvate dehydrogenase complex, is one of the late developers of tricarboxylic acid (TCA) cycle enzymes. The postnatal development of KGDHC in rat brain exhibits four distinct region-specific patterns. The age-dependent increases in olfactory bulb (OB) and hypothalamus (HYP) form one pattern: low in postnatal days (P) 2 and 4, KGDHC activity rose linearly to attain adult level at P30. The increases in mid-brain (MB) and striatum (ST) constitute a second pattern: being <40% of adult level at P2 and P4, KGDHC activity rose steeply between P10 and P17 and attained adult level by P30. The increases in cerebellum (CB), cerebral cortex (CC), and hippocampus (HIP) form a third pattern: being 25-30% of adult level at P2 and P4, KGDHC activity doubled between P10 and P17 and rose to adult level by P30. KGDHC activity development is unique in pons and medulla (PM): being >60% of the adult level at P2, it rose rapidly to adult level by P10. Thus, KGDHC activity develops earlier in phylogenetically older regions (PM) than in phylogenetically younger regions (CB, CC, HIP). Being lowest in activity among all TCA cycle enzymes, KGDHC activity in any region at any age will exert a limit on the maximum TCA cycle flux therein. The results may have functional and pathophysiological implications in control of brain glucose oxidative metabolism, energy metabolism, and neurotransmitter syntheses.

Animals↗
PubMed2000

Breakdown of tolerance to a neo-self antigen in double transgenic mice in which B cells present the antigen.

Transgenic (Tg) mice expressing a foreign Ag, hen egg lysozyme (HEL), under control of the alphaA-crystallin promoter ("HEL-Tg" mice) develop immunotolerance to HEL attributed to the expression of HEL in their thymus. In this paper we analyzed the immune response in double (Dbl)-Tg mice generated by mating the HEL-Tg mice with Tg mice that express HEL Abs on their B cells ("Ig-Tg" mice). The B cell compartment of the Dbl-Tg mice was unaffected by the HEL presence and was essentially identical to that of the Ig-Tg mice. A partial breakdown of tolerance was seen in the T cell response to HEL of the Dbl-Tg mice, i.e., their lymphocyte proliferative response against HEL was remarkably higher than that of the HEL-Tg mice. T-lymphocytes of both Dbl-Tg and Ig-Tg mice responded to HEL at concentrations drastically lower than those found stimulatory to lymphocytes of the wild-type controls. Cell mixing experiments demonstrated that 1) the lymphocyte response against low concentrations of HEL is due to the exceedingly efficient Ag presenting capacity of the Ab expressing B cells and 2) breakdown of tolerance in Dbl-Tg mice can also be attributed to the APC capacity of B cells, that sensitize in vivo and stimulate in vitro populations of T cells with low affinity toward HEL, assumed to be escapees of thymic deletion. These results thus indicate that T cell tolerance can be partially overcome by the highly potent Ag presenting capacity of Ab expressing B cells.

Animals↗
PubMed2000

Nonlinear determination of Michaelis-Menten kinetics with model evaluation through estimation of uncertainties.

A structured analytic approach was developed to evaluate enzyme kinetic parameters using non-linear least-squares fitting. The approach was implemented in a software package called KinSim and designed to run on Windows 95, 98, and NT platforms. The software and the theoretical approach were tested using kinetic data obtained using citrate synthase with acetyl CoA as a substrate and octanoyl CoA as an inhibitor. Using the software, the data were evaluated for statistical certainty of the presence of competitive and non-competitive inhibition of the enzyme. Given the determination of the presence of both components of inhibition in the experimental setup, the software was used to determine the inhibitory kinetics from the experimental data, including non-normal distributions of uncertainty. Finally, the software was used to evaluate the sensitivities of the experiment design at each concentration of substrate used. The theoretical approach as implemented in the user-friendly software allows investigators to use a structured procedure for evaluating and planning enzyme kinetic and related metabolic studies.

Acetyl Coenzyme A↗
PubMed2000

Bioadhesives for intraocular use.

BACKGROUND/PURPOSE: A safe, effective adhesive could be useful in the management of retinal holes or tears and selected complicated retinal detachments, as well as for attaching a small electronic device (retinal prosthesis) to the retina. In this study, we examined nine commercially available compounds for their suitability as intraocular adhesives. METHODS: The following materials were studied: commercial fibrin sealant, autologous fibrin, Cell-Tak, three photocurable glues, and three different polyethylene glycol hydrogels. An electronic strain gauge measured the adherence forces between different glues and the retina. The stability of hydrogels at body temperature and the impermeability of the hydrogel adhesive to dextran blue were examined. Long-term biocompatibility testing of the most promising glues in terms of adhesive force, consistency, and short-term safety (hydrogels) were done in rabbits. Funduscopy, electroretinogram, and histology of the retina were performed. RESULTS: Hydrogels had 2 to 39 times more adhesive force (measured in mN) than the other glues tested. They liquefied at body temperature after 3 days to a few months. Hydrogels were impermeable to dextran blue. One type of hydrogel proved to be nontoxic to the retina. CONCLUSIONS: Hydrogels proved to be superior for intraocular use in terms of consistency, adhesiveness, stability, impermeability, and safety.

Adhesiveness↗
PubMed2000

Consistency in choice of social referent.

Similarity has been an important but ill-defined concept in social comparison theory. For social comparisons of competence, similarity should be defined within the same evaluative social context, for example, the same school for students or the same workplace for workers. 104 postsecondary school students, 96 full-time university students, and 81 part-time mature university students were recruited to participate in this study. They filled out a questionnaire to indicate whether they compared themselves with each of 11 categories of social referent in each of 10 domains of competence. Comparers preferred to choose those in the same evaluative social context as referents for social comparisons in domains of competence, and their comparisons with dissimilar others were rare. This preference was consistent across the three different samples.

Achievement↗
PubMed2000

Health beliefs and optimism as predictors of preventive health decisions in Hong Kong Chinese.

The effects of components of the Health Belief Model and optimism on preventive intention were examined in 144 Hong Kong Chinese. Two variables related to the Health Belief Model, susceptibility and severity, were experimentally manipulated for an imaginary flu outbreak and a hypothetical vaccine. Participants indicated their intention to take the hypothetical vaccine after reading each of the 4 combinations of high versus low susceptibility and severity. Analysis suggested that both higher susceptibility and higher severity were associated with stronger behavioral intention to take the vaccine. Higher optimism scores were significantly associated with lower intention to take preventive action. In addition, a significant interaction was observed for optimism and severity. The effect of optimism was higher when severity was low than when it was high. Implications of these findings for research among Chinese were discussed.

Adult↗
PubMed1999

Bilateral ocular ischemic syndrome secondary to giant cell arteritis progressing despite corticosteroid treatment.

PURPOSE: To report the development of a bilateral ocular ischemic syndrome despite corticosteroid treatment in a patient with giant cell arteritis. METHOD: Case report. RESULTS: Despite receiving high-dose intravenous methylprednisolone and oral prednisone for biopsy-proven giant cell arteritis that presented as a severe anterior ischemic optic neuropathy in the right eye, a patient developed progressive ocular ischemia in that eye as well as an ocular ischemic syndrome in the fellow eye. CONCLUSIONS: Some patients with giant cell arteritis, possibly patients with other underlying systemic vasculopathies, are refractory to what should be adequate treatment with systemic corticosteroids and may develop a bilateral ocular ischemic syndrome.

Administration, Oral↗
PubMed1999

Hexokinase in astrocytes: kinetic and regulatory properties.

Hexokinase (HK, EC 2.7.1.1) is a key enzyme in the control of brain glucose metabolism. The regulatory role of HK in different neural cell types has not been elucidated. In this study we determined some kinetic and regulatory properties of HK in mouse cerebrocortical astrocytes in primary culture. Astroglial HK showed an absolute requirement for Mg-ATP and D-glucose. The pH optimum of HK was between 7.4 and 8.0. For astroglial HK, the Km for Mg-ATP was approximately 208 microM and Vmax approximately 35.4 mU/mg protein. At levels higher than 0.2 mM, D-glucose-1,6-bisphosphate, a known regulator of glycolysis, inhibited astroglial HK in a concentration-dependent manner, with an IC50 of approximately 0.4 mM; at 1.2 mM, it almost completely inhibited HK activity. The results obtained for astroglial HK are compatible with those reported for the highly purified preparations of brain HK. These data are of direct relevance to the assessment of glycolytic flux and its regulation in astrocytes.

Animals↗
PubMed1999

Uveitis induced by lymphocytes sensitized against a transgenically expressed lens protein.

PURPOSE: Previously established experimental models for lens-associated uveitis (LAU) are all mediated by antibodies. The present study analyzed the features of a novel experimental intraocular inflammatory eye disease that is mediated by lymphocytes targeted at a lens antigen. METHODS: Conventional technologies were used to generate three lines of transgenic (Tg) mice, expressing hen egg lysozyme (HEL) under the control of the alphaA-crystallin promoter. To induce intraocular inflammation, these Tg mice were injected with lymphocytes from syngeneic wild-type donors sensitized against HEL. Before their injection, the cells were stimulated in culture with HEL. To release lenticular material, some eyes were capsulotomized. Ocular histopathologic changes were examined by routine methods. Levels of HEL antibody were measured by enzyme-linked immunosorbent assay, whereas cellular immunity was determined by the lymphocyte proliferation assay. RESULTS: Intraocular inflammation developed in HEL-Tg mice injected with syngeneic lymphocytes sensitized against HEL. The severity of inflammation was directly related to the number of injected cells, as well as to the accessibility of HEL. The most intense inflammation was seen in Tg mice in which the lens was disintegrated due to high production of HEL. In mice with no apparent lenticular changes the inflammation was enhanced by capsulotomy. The inflammation affected all segments of the eye and persisted for at least 39 days after adoptive transfer of cells. Four days after cell injection, the inflammation consisted of subacute infiltration, with both mononuclear and polymorphonuclear leukocytes, whereas more chronic infiltration was seen at later times. Vigorous cellular immunity but no antibody to HEL was found in recipient mice, thus demonstrating the exclusive participation of cellular immunity in the pathogenesis of this experimental disease. CONCLUSIONS: Transgenic mice expressing HEL in their lenses develop intraocular inflammation after injection of syngeneic lymphocytes sensitized against HEL. This experimental disease is a novel cell-mediated model for LAU.

Adoptive Transfer↗
PubMed1998

Functional studies in cultured astrocytes.

Studies using primary cultures of astrocytes have made essential contributions to the understanding of astrocytic functions and neuronal-astrocytic interactions. The purposes of this article are to (i) outline principles and methodologies used in the preparation of such cultures and caveats for the interpretation of the observations made; (ii) summarize astrocytic functions in turnover of the amino acid transmitters glutamate and gamma-aminobutyric acid (GABA), in energy metabolism and in Na+,K+-ATPase-catalyzed processes and emphasize the degree to which the observations have been confirmed in intact tissue; (iii) describe regulations of astrocytic functions by transmitters and by calcium channel activity; and (iv) indicate suggestions for future functional studies using astrocytes in primary cultures and emphasize that some of the conclusions about neuronal-astrocytic interactions reached on the basis of studies in cultured cells and confirmed in intact tissue may not yet have been completely integrated into general neuroscience knowledge.

Adenosine Triphosphatases↗
PubMed1998

Aging is associated with a decrease in synaptosomal glutamate uptake and an increase in the susceptibility of synaptosomal vitamin E to oxidative stress.

We examined the influence of aging upon the uptake of glutamate by synaptosomes, and the oxidation of synaptosomal vitamin E. Synaptosomes isolated from the cerebral hemispheres of Fischer 344 rats, 4 and 24 months old, were suspended at 37 degrees C in buffer (pH 7.4) simulating extracellular fluid containing 10 mM glucose. The Km for the high affinity uptake of tritium labeled glutamate was approximately 10 microM. The uptake of glutamate was lower in synaptosomes from older animals than those from younger animals for periods of up to 20 minutes. Upon incubation with a mixture of ferrous iron and ascorbate, more of the alpha tocopherol in synaptosomes derived from older rats was oxidized than in those derived from younger ones. Older animals may be more susceptible to excitotoxicity because: a) synaptosomal reuptake of glutamate is less efficient and b) oxidative stress induced by various agents including glutamate may be higher in synaptosomes from the older animal.

Aging↗
PubMed1998

Topical liposome-encapsulated FK506 for the treatment of endotoxin-induced uveitis.

PURPOSE: Liposome preparations of FK506 improve the penetration of topically administered drug into the aqueous humor. The purpose of the experiment was to compare topically administered highdose oil-dissolved FK506 (OD-FK506) and low-dose liposome-bound FK506 (LB-506) for the treatment of endotoxin-induced uveitis (EIU). METHODS: Endotoxin-induced uveitis was produced in female Lewis rats with Salmonella typhimurium endotoxin. Four hours prior to endotoxin injection, one eye received 20 mul eyedrops every four hours containing either high-dose OD-FK506 at 3 mg/ml (N = 20), low-dose LB-FK506 at 0.16 mg/ml (N = 19), prednisolone acetate 1% (N = 20), or empty liposomes (N = 20). Eyes were enucleated 24 hours after endotoxin injection and inflammatory cells were counted on histologic sections by two masked observers. RESULTS: The mean number of infiltrating inflammatory cells per section +/- S.E.M. was 127.8 +/- 20.1, 76.8 +/- 16.7, 75.0 +/- 19.1, and 3.6 +/- 0.4 for animals treated with empty liposomes, LB-FK506, OD-FK506, and prednisolone acetate, respectively. The difference in inflammation between the empty liposome controls and the LB-FK506- and OD-FK506-treated animals was statistically significant (p = 0.03 and p = 0.02, respectively). The difference in inflammation between the high-dose OD-FK506- and low-dose LB-FK506-treated animals was not statistically significant (0 = 0.94). CONCLUSION: In this study, low-dose LB-FK506 and high-dose (OD-FK506) were both effective in inhibiting EIU. Higher concentrations of LB-FK506 are being developed and should augment the therapeutic effect of topical FK506.

Administration, Topical↗
PubMed1998

Immunotolerance against a foreign antigen transgenically expressed in the lens.

PURPOSE: To extend our knowledge concerning immunotolerance against autologous lens crystallins, transgenic (Tg) mice that express a foreign antigen in their lens were generated, and the immune response against the antigen in these mice was analyzed. METHODS: Conventional techniques were used to generate lines of Tg mice that express soluble (S-) or membrane-bound (M-) hen egg lysozyme (HEL) under the control of the alphaA-crystallin promoter. The presence of HEL in various organs was determined by the particle concentration fluorescence immunoassay (PCFIA), and reverse transcription-polymerase chain reaction technique was used to detect mRNA transcripts of the molecule. To examine the development of immunity (or tolerance), Tg mice and their wild-type controls were immunized with HEL (25 microg) in Freund's complete adjuvant and 14 days later were tested for immune response against the antigen. Cellular immunity was measured by the lymphocyte proliferation assay and cytokine production, and humoral immunity was determined by enzyme-linked immunosorbent assay. RESULTS: Eyes of the high copy number M-HEL Tg mice were dystrophic, with disrupted lens, whereas no morphologic changes were detected in the eyes of the other Tg mouse lines. All Tg mice exhibited tolerance to HEL by their cellular and humoral immune compartments. The state of immunotolerance to HEL was retained in the Tg mice for as long as 10 months after removal of the main depot of this protein, by enucleation. Measurable amounts of HEL were found in the eyes of all Tg mice, but the protein could not be detected in the serum or in other organs by the sensitive PCFIA (with a threshold of 1 ng/ml). Yet, HEL mRNA was found in the thymus of the Tg mice, suggesting that minute amounts of the protein are expressed in this organ. CONCLUSIONS: The unresponsiveness to HEL in the Tg mice seems to be due to a "central" mechanism of tolerance, mediated by a minuscule amount of HEL in the thymus. Conversely, the much larger amounts of HEL in the peripheral depot, the eyes, play a minor role if any in the tolerogenic process. It is further proposed that a similar mechanism of central tolerance is responsible for the immunotolerance against autologous lens crystallins.

Animals↗
PubMed1997

Permissive recognition of immunodominant determinants of the retinal S-antigen in different rat strains, primates and humans.

The majority of antigenic peptides exhibit restriction in their interaction with the MHC molecules on antigen-presenting cells of different haplotypes. Certain peptides, however, are "permissive': they bind strongly to different MHC molecules and are selected as the immunodominant epitopes by animals using these MHC gene products. Here we show for the first time that several peptides from four regions of the sequence of human S-antigen (H-SAg), a retinal-specific protein, demonstrate high levels of permissiveness. Each of these peptides was found to be immunodominant in at least some of four inbred rat strains and five cynomolgus monkeys, immunized with whole H-SAg. Moreover, some of these peptides were recognized by lymphocytes from four normal controls and four patients with uveitis who responded against the H-SAg molecule. On the other hand, the permissive peptides stimulated marginal or no response in cultures of Lewis rats injected with adjuvant alone, or rat and human cell lines specific to other antigens, thus demonstrating that these peptides do not carry any non-specific mitogenic activity. One peptide, 29, which was found immunodominant in the monkeys, the uveitis patients and Lewis rats, is highly immunopathogenic in this rat strain. No good correlation between immunodominance and immunopathogenicity was found with other H-SAg peptides. The finding of cross-species permissiveness among peptides of H-SAg and similar observations with myelin proteins suggest that permissiveness could be quite prevalent among peptides of immunopathogenic antigens.

Adult↗
PubMed1997

Complement-induced retinal arteriolar occlusions in the cat.

PURPOSE: To develop an animal model of complement-induced retinal vasculopathy and determine whether it resembles Purtscher's retinopathy. METHODS: Intravenous cobra venom factor was used to achieve intravascular activation of the complement system in cats. After a single bolus of cobra venom factor (75 units/kg), retinal blood flow was monitored at regular intervals by fluorescein angioscopy and angiography. RESULTS: Multiple small retinal arteriolar occlusions were present during the initial fluorescein transit of the immediate postinjection fluorescein study in 12 of 12 animals. Small, rapidly moving gaps in the fluorescein column were seen in two thirds of the animals observed continuously by fluorescein angioscopy. Angiographically, the obstructions were transient, and filling of the associated patches of capillary nonperfusion occurred within 3 minutes. Purtscher's-like ischemic retinal infarcts did not develop in any eye. Histopathologic analysis failed to demonstrate the nature of the transient vascular obstructive lesions, but indirect evidence suggested the possibility of granulocyte aggregates. CONCLUSION: Intravascular activation of the complement system produces transient microembolic retinal arteriolar occlusions in the cat. Although this model may represent a mild form of Purtscher's retinopathy, factors in addition to complement activation appear necessary to induce ischemic retinal infarcts.

Angioscopy↗