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Biomedical subjects

S Ho

Publications and source records attributed to S Ho.

At least 19 recordsLinked to original sources
PubMed2001

Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens.

Toll-like receptors (TLRs) are ancient microbial pattern recognition receptors highly conserved from Drosophila to humans. To investigate if subsets of human dendritic cell precursors (pre-DC), including monocytes (pre-DC1), plasmacytoid DC precursors (pre-DC2), and CD11c(+) immature DCs (imDCs) are developed to recognize different microbes or microbial antigens, we studied their TLR expression and responses to microbial antigens. We demonstrate that whereas monocytes preferentially express TLR 1, 2, 4, 5, and 8, plasmacytoid pre-DC strongly express TLR 7 and 9. In accordance with these TLR expression profiles, monocytes respond to the known microbial ligands for TLR2 (peptidoglycan [PGN], lipoteichoic acid) and TLR4 (lipopolysaccharide), by producing tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. In contrast, plasmacytoid pre-DCs only respond to the microbial TLR9-ligand, CpG-ODNs (oligodeoxynucleotides [ODNs] containing unmethylated CpG motifs), by producing IFN-alpha. CD11c(+) imDCs preferentially express TLR 1, 2, and 3 and respond to TLR 2-ligand PGN by producing large amounts of TNF-alpha, and to viral double-stranded RNA-like molecule poly I:C, by producing IFN-alpha and IL-12. The expression of distinct sets of TLRs and the corresponding difference in reactivity to microbial molecules among subsets of pre-DCs and imDCs support the concept that they have developed through distinct evolutionary pathways to recognize different microbial antigens.

Biomarkers↗
PubMed2001

Distinct cytokine profiles of neonatal natural killer T cells after expansion with subsets of dendritic cells.

Natural killer T (NKT) cells are a highly conserved subset of T cells that have been shown to play a critical role in suppressing T helper cell type 1-mediated autoimmune diseases and graft versus host disease in an interleukin (IL)-4-dependent manner. Thus, it is important to understand how the development of IL-4- versus interferon (IFN)-gamma-producing NKT cells is regulated. Here, we show that NKT cells from adult blood and those from cord blood undergo massive expansion in cell numbers (500-70,000-fold) during a 4-wk culture with IL-2, IL-7, phytohemagglutinin, anti-CD3, and anti-CD28 mAbs. Unlike adult NKT cells that preferentially produce both IL-4 and IFN-gamma, neonatal NKT cells preferentially produce IL-4 after polyclonal activation. Addition of type 2 dendritic cells (DC2) enhances the development of neonatal NKT cells into IL-4(+)IFN-gamma(-) NKT2 cells, whereas addition of type 1 dendritic cells (DC1) induces polarization towards IL-4(-)IFN-gamma(+) NKT1 cells. Adult NKT cells display limited plasticity for polarization induced by DC1 or DC2. Thus, newly generated NKT cells may possess the potent ability to develop into IL-4(+)IFN-gamma(-) NKT2 cells in response to appropriate stimuli and may thereafter acquire the tendency to produce both IL-4 and IFN-gamma.

Adult↗
PubMed2001

Effect of light on 5-methoxyindole-3-acetic acid in the rat.

This study aims to determine the effects of light on the levels of 5-MIAA to provide further information on this indoleamine, using a sensitive and specific radioimmunoassay (RIA) for immunoreactive 5-methoxyindole-3-acetic acid (5-MIAA) developed in our laboratories using a specific antibody and tritiated label. Significant differences were found in the immunoreactive 5-MIAA levels between mid-light and mid-dark pineal glands in rats adapted to 12/12 hrs light/dark and in constant darkness. Under constant light, the circadian rhythm was abolished. The rat serum displayed no diurnal variations in 5-MIAA levels under aux photic conditions. The persistence of rhythms found in constant darkness but abolished in constant light suggests that the pineal 5-MIAA is endogenous and uses light as an environmental cue. In addition to melatonin, 5-MIAA could possibly be another pineal photoperiodic signal in animals.

Animals↗
PubMed2001

HLA class II alleles in Chinese patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Recent reports of an association between human leucocyte antigens (HLA) and persistence of hepatitis B virus infection, and the familial clustering of hepatocellular carcinoma raise the question of genetic susceptibility. Previous studies have been limited to serological phenotyping of HLA B and DR antigens. The aim of this study was to use molecular genotyping to investigate HLA class II as a risk factor for the development of hepatocellular carcinoma in Hong Kong Chinese. METHODS: We determined HLA DRB1, DQA1, DQB1 and DPB1 alleles in 123 hepatitis B surface antigen positive patients (84 with hepatocellular carcinoma and 39 without) and 124 matched controls. RESULTS: The alleles DRB1*1501 (36% of HCC patients versus 19% of controls, odds ratio=2.44), DQA1*0102 (42% versus 26%, odds ratio=2.07), and DPB1*0501 (80% versus 63%, odds ratio=2.35) were significantly more common in patients with hepatocellular carcinoma, and DQA1*03 (36% versus 56%, odds ratio=0.53), DQB1*0302 (4.% versus 13%, odds ratio=0.25) and DPB1*0201 (14% versus 29%, odds ratio=0.4) were found at significantly lower frequencies. CONCLUSIONS: Although none of these associations was significant after correction for multiple testing, this report suggests that further investigations are warranted.

Adolescent↗
PubMed2001

Melatonin protects against cardiac toxicity of doxorubicin in rat.

Doxorubicin (DOX) is commonly used for the treatment of hematological and solid tumors. However, there are serious toxic effects on the cardiovascular system, which limits the application of the drug. Recently, melatonin has been reported to have immunomodulatory effect in addition to lowering cholesterol levels as well as inhibiting malignant tumors. In this study, the effect of melatonin against the toxicity of doxorubicin was investigated in rats. Hemodynamic function, pathological and biochemical changes were determined in different treated hearts. Our findings showed that a significant protection by melatonin (6 mg kg(-1) for 15 days, cumulative dose of 90 mg kg(-1)) against the DOX-induced toxicity was observed. Cardiac function was improved and lipid peroxidation decreased after melatonin treatment. It is concluded that melatonin provides protection against doxorubicin toxicity via an attenuation of lipid peroxidation.

Animals↗
PubMed2001

Admission angiography for blunt splenic injury: advantages and pitfalls.

BACKGROUND: To analyze the use of admission angiography as a nonoperative adjunct for management of blunt splenic injury. METHODS: Retrospective chart review of all blunt splenic injuries to a Level I trauma center from March 1997 through July 1999. RESULTS: One hundred twenty-six patients underwent angiography for splenic injury. Eighty-six patients (68%) had a negative angiogram and were treated expectantly. Of these, seven patients (8%) required laparotomy, with a splenic salvage rate of 92%. Embolization was performed on 40 patients (32%) for evidence of vascular injury. Of these, three patients (8%) required laparotomy, for a total salvage of 92%. Repeat angiography was performed for suspicion of bleeding in 12 patients (10%), with 50% requiring embolization. Outcome based on CT grade demonstrated an average grade of 2.9, with a salvage rate of greater than 70% for grade IV and V injuries. CONCLUSION: Vascular injury increases with splenic injury grade. Embolization improves nonoperative salvage rates to 92%, even with high-grade injuries. Ten percent of patients require additional therapy including "second-look" angiography. A significant portion of patients with negative screening angiograms (10%) required either embolization or laparotomy to control delayed hemorrhage.

Adult↗
PubMed2001

Sugar coordinately and differentially regulates growth- and stress-related gene expression via a complex signal transduction network and multiple control mechanisms.

In plants, sugars are required to sustain growth and regulate gene expression. A large set of genes are either up- or down-regulated by sugars; however, whether there is a common mechanism and signal transduction pathway for differential and coordinated sugar regulation remain unclear. In the present study, the rice (Oryza sativa cv Tainan 5) cell culture was used as a model system to address this question. Sucrose and glucose both played dual functions in gene regulation as exemplified by the up-regulation of growth-related genes and down-regulation of stress-related genes. Sugar coordinately but differentially activated or repressed gene expression, and nuclear run-on transcription and mRNA half-life analyses revealed regulation of both the transcription rate and mRNA stability. Although coordinately regulated by sugars, these growth- and stress-related genes were up-regulated or down-regulated through hexokinase-dependent and/or hexokinase-independent pathways. We also found that the sugar signal transduction pathway may overlap the glycolytic pathway for gene repression. alpha-Amylase and the stress-related genes identified in this study were coordinately expressed under sugar starvation, suggesting a convergence of the nutritional and environmental stress signal transduction pathways. Together, our studies provide a new insight into the complex signal transduction network and mechanisms of sugar regulation of growth and stress-related genes in plants.

DNA, Complementary↗
PubMed2001

Critical role of central facilitation in the glottic closure reflex.

The sphincteric function of the larynx, essential to lower airway protection, is most efficiently achieved through strong reflex adduction by both vocal cords. We hypothesize that central facilitation is an essential component of a bilateral adductor reflex and that its disturbance could result in weakened sphincteric closure. Six adult 50-kg pigs underwent evoked response laryngeal electromyography under 0.5 to 1.0 minimal alveolar concentration (MAC) isoflurane anesthesia. The internal branch of the superior laryngeal nerve was stimulated through bipolar platinum-iridium electrodes, and recording electrodes were positioned in the ipsilateral and contralateral thyroarytenoid muscles. Consistent threshold responses were obtained ipsilaterally from 0.5 to 1.0 MAC anesthesia. However, the contralateral reflex responses approached 0% in successive trials as anesthetic levels approached 1.0 MAC. Alteration of central facilitation by deepening anesthesia abolishes the crossed adductor reflex, predisposing to a weakened glottic closure response. A precise understanding of this effect may improve the prevention of aspiration in patients emerging from prolonged sedation or under heavy psychotropic control.

Anesthesia↗
PubMed2000

Generation of interferon alpha-producing predendritic cell (Pre-DC)2 from human CD34(+) hematopoietic stem cells.

Upon viral stimulation, the natural interferon (IFN)-alpha/beta-producing cells (IPCs; also known as pre-dendritic cells (DCs 2) in human blood and peripheral lymphoid tissues rapidly produce huge amounts of IFN-alpha/beta. After performing this innate antiviral immune response, IPCs can differentiate into DCs and strongly stimulate T cell-mediated adaptive immune responses. Using four-color immunofluorescence flow cytometry, we have mapped the developmental pathway of pre-DC2/IPCs from CD34(+) hematopoietic stem cells in human fetal liver, bone marrow, and cord blood. At least four developmental stages were identified, including CD34(++)CD45RA(-) early progenitor cells, CD34(++)CD45RA(+) late progenitor cells, CD34(+)CD45RA(++)CD4(+)interleukin (IL)-3Ralpha(++) pro-DC2, and CD34(-)CD45RA(++) CD4(+)IL-3Ralpha(++) pre-DC2/IPCs. Pro-DC2s have already acquired the capacity to produce large amounts of IFN-alpha/beta upon viral stimulation and to differentiate into DCs in culture with IL-3 and CD40 ligand. CD34(++)CD45RA(-) early progenitor cells did not have the capacity to produce large amounts of IFN-alpha/beta in response to viral stimulation; however, they can be induced to undergo proliferation and differentiation into IPCs/pre-DC2 in culture with FLT3 ligand.

Antigens, CD34↗
PubMed2000

A GDP-fucose-protected, pyridoxal-5'-Phosphate/NaBH(4)-sensitive lys residue common to human alpha1-->3Fucosyltransferases corresponds to Lys(300) in FucT-IV.

Human alpha1-->3/4fucosyltransferases (FucTs) contain a common essential pyridoxal-5'-phosphate(PLP)/NaBH(4) reactive, GDP-fucose-protectable Lys. For identification, site-directed mutants at lysines of FucT-IV and -VII were prepared and tested. Non conserved lysine mutants K119Y and K394Q were similar to wild-type FucT-IV. However, mutants of conserved lysines K228R and K300R were distinct. The specific activity of K228R was 2- to 3-fold lower but retained K(m) values for donor and acceptor substrates as wild-type FucT-IV. The specific activity of K300R was reduced over 400-fold with an apparent K(m) for GDP-fucose over 200 microM. FucT-VII mutants K169R and K240R (equivalent to K228R and K300R for FucT-IV, respectively) were inactive. No change in PLP/NaBH(4) sensitivity occurred with K119Y, K228R, and K394Q compared to wild-type FucT-IV. These and previous results (A. L. Sherwood, A. T. Nguyen, J. M. Whitaker, B. A. Macher, M. R. Stroud, and E. H. Holmes, J. Biol. Chem. 273, 25256-25260, 1998) demonstrate that of three conserved lysines in FucT-IV, two (Lys(228) and Lys(283)) are not involved in substrate binding but perhaps in catalysis. The third site, Lys(300), is involved in GDP-fucose binding and PLP/NaBH(4) inactivation.

Amino Acid Sequence↗
PubMed2000

The human anti-bullous pemphigoid monoclonal autoantibody P22 is encoded by genes of the IGHV4 and IGLV4 families.

We identified, cloned, and biochemically characterized the full-length cDNAs encoding the heavy and light chains of a human monoclonal antibody (mAb) from the Epstein-Barr virus (EBV)-cell line P22. The cell line P22, which originated from a patient with bullous pemphigoid (an autoimmune disease causing skin blistering) expressed immunoglobulin-G (IgG) with a lambda light chain. Although the variable heavy (IGHV) chain gene family could not be assigned by IGHV repertoire analysis, the determination of its nucleotide sequence demonstrated that the heavy chain of P22 belonged to the IGHV4 family. The limited IGHV4 gene usage by memory IgG, IGA and IgE-expressing cells supports the notion of the autoreactivity-associated IGHV4 genes and stresses the strong selection pressure within germinal centres towards IGHV4 family. Alignment of P22 IGHV4 cDNA sequence to germline sequences from gene databases, revealed a remarkable divergence, suggesting that the heavy chain of the P22 mAb encodes a distinct IGHV4 gene. The variable light chain (IGLV) encodes a IGLV4 gene and is 98% similar to a previously reported IGLV gene. Furthermore, fluorescent staining with the recombinant mAb showed the same reactivity to that of the native antibody. The data reported herein, (a) reveal an autoantibody encoding a distinct IGHV4 gene, (b) confirm the notion that autoantibodies preferentially use IGHV4 genes, and (c) hypothesize that somatic hypermutation within GC may be a mechanism by which autoreactive B lymphocytes escape negative selection.

Amino Acid Sequence↗
PubMed2000

Joint position during anterior-posterior glide mobilization: its effect on glenohumeral abduction range of motion.

OBJECTIVE: To investigate the effect of joint position during an anterior-posterior glide (APG) procedure on the range of motion (ROM) of glenohumeral abduction in cadaver specimens. DESIGN: Mechanical simulation of APG mobilization and abduction torque ROM measurement of the glenohumeral joint with a material testing system. The immediate mechanical efficacy of APG was compared in two groups of specimens at two different joint positions: midrange (n = 5) and end range (n = 6) of glenohumeral abduction. SETTING: Biomechanics laboratory. SPECIMENS: Eleven fresh cadaver shoulder specimens (mean age, 66.9+/-2.5 yrs). MAIN OUTCOME MEASURE: Improvement in glenohumeral abduction torque ROM obtained before and after APG procedure. RESULTS: Glenohumeral abduction improved significantly, as indicated by a significant increase (Kruskal-Wallis statistics, chi2 = 7.50, p = .006) in the torque ROM of the end range group (mean +/- standard error of the mean, 2.02 degrees +/- .20 degrees) over the midrange group (.64 degrees +/- .08 degrees). A significant difference in the magnitude of peak displacement of the humeral head between midrange (14.44+/-3.56 mm) and end range (3.19+/-.81 mm) groups was also found (Mann-Whitney test, p < .030). CONCLUSION: This study demonstrated that APG technique performed at close to the end of the range of abduction is more effective in improving glenohumeral abduction ROM than that performed at the middle of the range of abduction.

Aged↗
PubMed2000

Immediate response of glenohumeral abduction range of motion to a caudally directed translational mobilization: a fresh cadaver simulation.

OBJECTIVE: To investigate the immediate effect of caudal glide translational mobilization on the range of motion (ROM) of passive glenohumeral abduction with a fresh cadaver model to simulate the mobilization movement performed by a physical therapist treating patients with glenohumeral hypomobility. DESIGN: Mechanical simulation of caudal glide mobilization and abduction torque range of motion (TROM) measurement of the glenohumeral joint with 2 material testing systems. Mobilizations were conducted with the glenohumeral joint positioned at a resting position (IGR) and at the end range of abduction (IGE). SETTING: Biomechanics laboratory. CADAVERS: Twenty fresh shoulder specimens from 10 cadavers (mean age, 68 +/- 8 yr). MAIN OUTCOME MEASURE: Changes in TROM of the glenohumeral abduction in response to 5 bouts of caudal glide mobilization. RESULTS: At least 3 repetitions of TROM were required to attain consistent measurements on glenohumeral abduction ROM. Significant differences were found among changes in TROM because of rest, IGR, and IGE (Kruskal-Wallis statistics, (chi2 = 14.58, p = .001). A greater increase in glenohumeral abduction TROM was found after IGE (mean +/- standard error of the mean, 4.38 degrees +/- 0.95 degrees) compared with the rest control (0.03 degrees +/- 0.07 degrees; Mann-Whitney test, p = .001, alpha = .017) or its IGR counterpart (0.26 degrees +/- 0.46 degrees, p = .001, alpha = .017). CONCLUSION: This simulation of caudal glide translational mobilization at the end range using cadaver models improved passive glenohumeral abduction ROM but was ineffective when performed with the shoulder placed in a resting position. The mechanical responses of the glenohumeral joint to translational mobilization in a live patient may be similar, but some caution should be used in generalizing these findings.

Aged↗