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Biomedical subjects

J H Lai

Publications and source records attributed to J H Lai.

At least 19 recordsLinked to original sources
PubMed2005

Sweet's syndrome as an initial presentation in systemic lupus erythematosus: a case report and review of the literature.

Malar or discoid rash is the most frequent specific cutaneous lesion for systemic lupus erythematosus (SLE). Neutrophilic dermatosis as an initial presentation in SLE is unusual. We describe a 38-year old female patient who primarily suffered from erythematous tender plaques and fever. Examination of skin biopsy of the plaques showed dense neutrophilic infiltration in the dermis. Polyarthritis, heavy proteinuria, photosensitivity and positive antinuclear antibodies (ANA > 1:1280) concluded the diagnosis of SLE. The plaques disappeared completely after treatment with systemic corticosteroids. To our knowledge, this is the first reported SLE patient with Sweet's syndrome as the initial presentation in literature review.

Adult↗
PubMed2004

Organosilicon dental composite restoratives based on 1,3-bis[(p-acryloxymethyl) phenethyl] tetramethyldisiloxane.

OBJECTIVES: The major concern associated with the use of polysiloxanes as polymer matrices in dental restorative materials, is the generally modest mechanical properties of the polymers. However, it has long been demonstrated that thermal stability, and mechanical properties of polysiloxanes can be substantially modified by incorporation of bulkier substituents such as phenyl groups or more polar groups in the chains. The purpose of this research was to evaluate visible light activated dental composites based on the high molecular weight siloxane monomer 1,3-bis[(p-acryloxymethyl) phenethyl] tetramethyldisiloxane (BAPD). METHODS: Hardness, diametral tensile strength (DTS), degree of conversion (DC), water sorption (WS) and polymerization shrinkage of BAPD-based composites and bis-GMA-based composites were determined and compared. RESULTS: Composites based on BAPD exhibited low WS, high DC, low polymerization shrinkage, and had hardness and DTS values that were not significantly lower than those of dental composites based on bis-GMA. SIGNIFICANCE: BAPD is a high molecular weight monomer (MW = 511) with a low viscosity. It did not require the use of low molecular weight diluent monomers in formulating composite resins. The DC of BAPD was high, ranging from 86 to 94%. Although the DC of BAPD was significantly higher than the conventional difunctional dental monomers, the polymerization shrinkage of the siloxane composites (1.70 - 1.81 vol%) was comparable to several composites based on bis-GMA.

Absorption↗
PubMed2004

Dehydroepiandrosterone suppresses interleukin 10 synthesis in women with systemic lupus erythematosus.

OBJECTIVE: To study the effects of dehydroepiandrosterone (prasterone, DHEA) 200 mg/day on cytokine profiles in adult women with active systemic lupus erythematosus (SLE). METHODS: In a double blind, randomised, placebo controlled study conducted as part of a larger multicentre study, 30 adult women with active SLE received oral DHEA 200 mg/day or placebo for 24 weeks. Baseline prednisone (<10 mg/day) and other concomitant SLE medications were to remain constant. The levels of cytokines including interleukin (IL) 1, IL2, interferon gamma, IL4, and IL10 were determined by ELISA. The mean change from baseline to 24 weeks of therapy was analysed. RESULTS: The two groups (DHEA n = 15; placebo n = 15) were well balanced for baseline characteristics. Only IL1beta and IL10 could be detected in the serum of lupus patients; however, there was no significant mean (SD) difference in serum IL1beta before and after treatment (9.94 (8.92) v 9.20 (6.49) pg/ml). IL10 demonstrated a greater and significant reduction from baseline (9.21 (9.66) to 1.89 (1.47) pg/ml in the DHEA treatment group). CONCLUSIONS: In a 24 week study of adult Chinese women with mild to moderate SLE, treatment with DHEA 200 mg once daily resulted in significant reduction of serum levels of IL10. This finding may suggest why DHEA could significantly reduce lupus flares.

Adolescent↗
PubMed2003

Ruptured renal microaneurysms complicated with a retroperitoneal abscess for a patient with systemic lupus erythematosus.

Renal artery aneurysm is extremely rare among patients with systemic lupus erythematosus.(SLE). Herein, we report on a 22-year-old male lupus patient who presented with acute abdominal pain, anemia and subsequent hypertension. Abdominal computed tomography revealed a peri-renal hematoma over the right kidney. A renal angiography revealed bilateral renal microaneurysms. The patient subsequently developed a right-side retroperitoneal abscess 4 weeks after hematoma formation and received an emergent laparotomy with drainage. Subsequent culture ofthe abscess-derived fluid revealed the presence of Proteus mirabilis and Escherichia coli. Following appropriate antipyretic and immunosuppressive drugs therapy, the patient recovered successfully. To the best of our knowledge, this is the first report of SLE associated with a retro-peritoneal abscess probably secondary to a ruptured renal microaneurysm.

Abdominal Abscess↗
PubMed2002

New organosilicon maxillofacial prosthetic materials.

OBJECTIVES: The silicone elastomer A-2186 is a widely used maxillofacial prosthetic material. It is a pourable two-component silicone rubber cured by a platinum catalyst. Used as a prosthetic material, A-2186 has short working time and because of its hydrophobic nature, poor adhesion to non-silicone based adhesives. The purpose of this study is to evaluate the physical properties of new prosthetic materials based on methacryloxypropyl-terminated polydimethylsiloxane (MPDS-MF), and to compare the properties with those of A-2186. METHODS: Hardness, tensile strength, ultimate elongation, tear strength and adhesive bonding strength of MPDS-MF and A-2186 with and without additives were determined and compared. The bonding strengths of the extrinsic colorant carrier with the prosthetic materials were also determined. Statistical analyses were done using a two-way analysis of variance (ANOVA). For significant effects, post-hoc tests were done using the Bonferroni correction. RESULTS: The hardness of MPDS-MF is similar to A-2186. However, tensile strength, tear strength, ultimate elongation, and adhesive bonding strength of MPDS-MF are higher than those of A-2186. SIGNIFICANCE: MPDS-MF is cured by free radical thermal polymerization and crosslinking. The working time of MPDS-MF, unlike A-2186, is long. The presence of methacrylate groups in MPDS-MF enhances its adhesion to non-silicone based adhesive. Based on the present study, it appears that MPDS-MF is suitable for use in fabricating of clinical prostheses.

Adhesives↗
PubMed2002

[Cloning and analysis of a novel gene encoding N-terminal acetyltransferase subunit].

N-terminal acetylation is the most common modification in eukaryotic proteins, affecting stability and activity of proteins. NatA is one of the N-terminal acetytransferases in yeast. It is composed of two subunits, NAT1 and ARD1. Defect in one of them leads to loss of activity of NatA. Null mutant of NAT1 in yeast exhibits a variety of phenotypes, including depression of a silent mating type locus (HML), failing to enter G(0) in poor nutrient situations and chromosomes instability. Based on homology of NAT1 between yeast and other organisms, the full-length CDS (coding sequence) of HNAT1 was cloned and sequenced. Result of in situ hybridization in testis of rat showed that expression of NAT1 was high and its expression was different in different phases of spermatogenesis. The gene may play an important role in spermatogenesis.

Acetyltransferases↗
PubMed2001

Western and Chinese antirheumatic drug-induced T cell apoptotic DNA damage uses different caspase cascades and is independent of Fas/Fas ligand interaction.

Spontaneous or therapeutic induction of T cell apoptosis plays a critical role in establishing transplantation tolerance and maintaining remission of autoimmune diseases. We investigated the mechanisms of apoptosis induced by Chinese and Western antirheumatic drugs (ARDs) in human T cells. We found that hydroxychloroquine, Tripterygium wilfordii hook F, and tetrandrine (Tet), but not methotrexate, at therapeutic concentrations can cause T cell death. In addition, Tet selectively killed T cells, especially activated T cells. Although ARD-induced cytotoxicity was mediated through apoptotic mechanisms, Fas/Fas ligand interaction was not required. We further demonstrated that the processes of phosphatidylserine externalization and DNA damage along the ARD-induced T cell apoptotic pathway could operate independently, and that selective inhibition of DNA damage by caspase inhibitors did not prevent T cells from undergoing cell death. Moreover, we found that Tet- and Tripterygium wilfordii hook F-induced T cell DNA damage required caspase-3 activity, and hydroxychloroquine-induced T cell DNA damage was mediated through a caspase-3- and caspase-8-independent, but Z-Asp-Glu-Val-Asp-fluomethyl ketone-sensitive, signaling pathway. Finally, the observation that ARD-induced activation of caspase-3 in both Fas-sensitive and Fas-resistant Jurkat T cells indicates that Fas/Fas ligand interaction plays no role in ARD-induced T cell apoptosis. Our observations provide new information about the complex apoptotic mechanisms of ARDs, and have implications for combining Western and Chinese ARDs that have different immunomodulatory mechanisms in the therapy of autoimmune diseases and transplantation rejection.

Alkaloids↗
PubMed2001

Infection of human dendritic cells by dengue virus causes cell maturation and cytokine production.

Dengue virus (DV) infection is a major problem in public health. It can cause fatal diseases such as Dengue hemorrhagic fever and Dengue shock syndrome. Dendritic cells (DC) are professional APCs required for establishing a primary immune response. Here, we investigated the role of human PBMC-derived DC in DV infection. Using different techniques, including plaque assay, flow cytometry analysis, nested RT-PCR, and confocal microscope and electron microscope examinations, we show that DV can enter cultured human DC and produce virus particles. After entrance, DV could be visualized in cystic vesicles, vacuoles, and the endoplasmic reticulum. The DV-infected DC also showed proliferation and hypertrophy of the endoplasmic reticulum as well as the swollen mitochondria. In addition, the DV-stimulated DC could express maturation markers such as B7-1, B7-2, HLA-DR, CD11b, and CD83. Furthermore, the infection of DC by DV induced production of TNF-alpha and IFN-alpha, but not IL-6 and IL-12. Although DC underwent spontaneous apoptosis in the absence of feeding cytokines, this process appeared to be delayed after DV infection. Our observations provide important information in understanding the pathogenesis of DV infection.

Apoptosis↗
PubMed2001

Aspirin differentially regulates endotoxin-induced IL-12 and TNF-alpha production in human dendritic cells.

OBJECTIVE: In the development of autoimmune diseases, dendritic cells (DC) play critical roles. Here, we examined the effect of aspirin on lipopolysaccharide (LPS)-induced DC activation. METHODS: The monocyte-derived DC were established. The cytokine production was measured by ELISA, reverse transcriptase/polymerase chain reaction, or intracellular staining analyzed by flow cytometry. The expression of cell surface molecules was determined by flow cytometry. RESULTS: Aspirin inhibited LPS-induced DC maturation and costimulatory molecules expression. Aspirin, at therapeutic concentrations, also decreased LPS-induced IL-12 and IL-10 production. In contrast, the LPS-induced TNF-alpha production was enhanced by aspirin. The differential effects of aspirin on IL-12 and TNF-alpha production may not be due to down-regulation of cyclooxygenase activities. CONCLUSION: The various effects of aspirin on LPS-stimulated DC may influence the understanding of the diverse immunomodulatory mechanisms of this anti-inflammatory drug.

Aspirin↗
PubMed2001

Development of a nondestructive compliance test for resilient denture liners.

PURPOSE: Resilient denture liners are prescribed for patients who cannot adjust to hard-based dentures because of a thin mucosa or severe alveolar ridge resorption. A nondestructive test to evaluate compliance of new soft liner materials will be useful in clinical trials. The purpose of this study was to evaluate a nondestructive compliance testing technique designed to characterize long-term, silicone-based resilient denture liner materials. MATERIALS AND METHODS: Samples of thicknesses of 1.1, 2.2, 3.3, and 4.4 mm of 2 materials (MPDS-SL [Lai Laboratories, Inc, Burnsville, MN] and Molloplast-B [Buffalo Dental, New York, NY]) were assessed for compliance using a closed-loop servohydraulic testing system, applying a 3 lb force following a squarewave pattern; force and position values were recorded using a storage oscilloscope. The oscilloscope values were analyzed using computer software to determine compliance values. The effect of material thickness was examined by testing wedges of the 2 materials. RESULTS: The testing technique used showed that differing thicknesses had significantly different compliance values (p <.0001). In the materials used to evaluate the technique, MPDS-SL behaved more elastically than did Molloplast-B (p <.0001). Material thicknesses beyond 2.2 mm did not increase compliance, although MPDS-SL had a steeper thickness-compliance curve than Molloplast-B. CONCLUSIONS: The method used to test compliance proved to be sufficiently sensitive to distinguish between 2 materials and between varying thicknesses. The sensitivity and nondestructive nature of this test show its suitability for clinical evaluation of resilient denture liners.

Analysis of Variance↗
PubMed2001

[Genetic polymorphisms of 9 STR loci in Achang ethnic group in Yunnan Province].

Blood samples were collected from the unreleatled individuals in the Achang ethnic group in Yunnan Province. Genetic distribution for nine STR loci and amelogenin locus were determined in Achang ethnic group based on GeneScan. 96 samples were denatured of gel electrophoresis. The databanks in Achang ethnic group were generated by using GeneScan, genotyper, and genetic distribution analysis. 69 alleses and 166 genotypers were observed, with the corresponding frequency being 0.0050-0.6100 and 0.0100-0.3900. The average H is 0.7381. The comulated DP is 0.9999999. The comulated EPP is 0.9999989. The allele distribution of the loci was in good agreement with the Handy-Weibeng equilibrium. It is useful to establishing DNA databanks for studying gene natural resources, very valuable in the study of forensic science, anthropology and ethnic.

Amelogenin↗
PubMed2000

Utilization of oriented peptide libraries to identify substrate motifs selected by ATM.

The ataxia telangiectasia mutated (ATM) gene encodes a serine/threonine protein kinase that plays a critical role in genomic surveillance and development. Here, we use a peptide library approach to define the in vitro substrate specificity of ATM kinase activity. The peptide library analysis identified an optimal sequence with a central core motif of LSQE that is preferentially phosphorylated by ATM. The contributions of the amino acids surrounding serine in the LSQE motif were assessed by utilizing specific peptide libraries or individual peptide substrates. All amino acids comprising the LSQE sequence were critical for maximum peptide substrate suitability for ATM. The DNA-dependent protein kinase (DNA-PK), a Ser/Thr kinase related to ATM and important in DNA repair, was compared with ATM in terms of peptide substrate selectivity. DNA-PK was found to be unique in its preference of neighboring amino acids to the phosphorylated serine. Peptide library analyses defined a preferred amino acid motif for ATM that permits clear distinctions between ATM and DNA-PK kinase activity. Data base searches using the library-derived ATM sequence identified previously characterized substrates of ATM, as well as novel candidate substrate targets that may function downstream in ATM-directed signaling pathways.

Amino Acid Motifs↗
PubMed2000

[STR polymorphisms in five Chinese ethnic groups(2)].

Population genetic studies were performed in Chinese Han, Hui, Mongolian, Tibetan and Uygur. Allele frequency distributions were analyzed for ten loci, i.e., D3S1358, VWA, CSF1PO, FGA, THO1, TPOX, D5S818, D13S317 and D7S820 by GeneScan. The results showed that there were 60 STR alleles and 149 genotypes in Han; 63 STR alleles and 144 genotypes in Hui; 69 STR alleles and 173 genotypes in Mongolian; 77 STR alleles and 168 genotypes in Tibetan; 70 STR alleles and 148 genotypes in Uygur. Significant differences were identified among ethnic groups (African-American, US-Caucasian and Chinese-Oriental), but similarity was found among the five Chinese populations, and immunogenomics and pharmacogenomics studied in this report. These findings indicated that the nine STR loci and amelogenin locus were very useful for individual identification in forensic science.

Alleles↗
PubMed1999

Plant alkaloid tetrandrine and its analog block CD28-costimulated activities of human peripheral blood T cells: potential immunosuppressants in transplantation immunology.

BACKGROUND: T lymphocyte activation mediated by CD28 costimulation plays a critical role in graft rejection. Plant alkaloid tetrandrine, purified from a Chinese antirheumatic herb, is a potent immunosuppressant. Here, we examined its effects on several CD28-costimulated T-cell activities. In addition, such effects were readily compared with the effects of three tetrandrine analogs. METHODS: T lymphocytes were purified from whole blood by negative selection. The stimuli that mimic CD28 costimulation included both anti-CD3 + anti-CD28 monoclonal antibody and PMA+anti-CD28 monoclonal antibody. The determination of CD28-costimulated cell proliferation was performed by tritium uptake, cytokine production by ELISA, cell surface interleukin 2Ra and CD69 expression by flow cytometry, and mixed leukocyte reaction by tritium uptake. Drug cytotoxicity was determined by trypan blue exclusion, propidium iodide staining, and MTT colorimetric assays. RESULTS: Tetrandrine inhibited CD28-costimulated T-cell proliferation and cytokine production through a mechanism different from that of cyclosporine. In addition, tetrandrine down-regulated both T helper 1 and T helper 2 cytokine production in CD4+ and CD8+ T-cell subpopulations. By examining cytokine production and T-cell activation marker expression, we further demonstrated that, among tetrandrine and its analogs tested, dauricine was the most potent suppressor of CD28-costimulated T-cell activities. Furthermore, the different immunosuppressive activities of these compounds were not associated with their cytotoxic capacities. Finally, the unparalleled inhibitory potency of dauricine on both mixed leukocyte reaction and CD28-costimulated T-cell proliferation suggests that dauricine preferentially targeted CD28-costimulated T-cell activities. CONCLUSIONS: This is the first report to show that tetrandrine and its analogs potently inhibited both PMA+CD28-costimulated and CD3 + CD28-costimulated activation of human peripheral blood T cells. Based upon their structural similarity and different immunosuppressive potency, these in vitro data also provide very useful information for further identification and development of more potent and less toxic immunosuppressants to achieve transplantation success.

Alkaloids↗
PubMed1999

Plant alkaloid tetrandrine downregulates protein kinase C-dependent signaling pathway in T cells.

Tetrandrine, a purified traditional Chinese medicinal herb that acts as an immunosuppressant and a Ca2+ channel blocker, has been clinically used to treat patients with arthritis, silicosis and hypertension. Since T cells play a critical role as autoreactive and pathogenic population in autoimmune diseases, in this study, we examined the immunosuppressive effect of tetrandrine on human peripheral blood T cells. We showed that tetrandrine inhibited phorbol 12-myristate 13-acetate (PMA) + ionomycin-induced T cell proliferation, interleukin-2 secretion and the expression of the T cell activation antigen, CD71. Further investigation of the molecular mechanism demonstrated that tetrandrine inhibited the expression of the protein kinase C-dependent interleukin-2 receptor alpha chain and CD69 but not the expression of the Ca2+-dependent CD40 ligand and CD69. Interestingly, when tetrandrine and cyclosporin A were added together, significant synergism in the suppression of T cell activation was observed. Moreover, of the several tetrandrine analogues studied, hernandezine was the most potent inhibitor of protein kinase C signaling events. These results also suggest that the protein kinase C-inhibitory capacity of tetrandrine and its analogues may not be associated with their function as Ca2+ channel blockers. Lastly, we showed that, within therapeutic concentrations, tetrandrine and its analogues could induce cellular apoptosis, which is defective in autoimmune diseases. In conclusion, our findings provide novel information about the molecular mechanism of the immunosuppressive effect of tetrandrine and its analogues in human peripheral blood T cells.

Alkaloids↗