PubMed Health⌕ Search

Biomedical subjects

C Y Ho

Publications and source records attributed to C Y Ho.

At least 19 recordsLinked to original sources
PubMed2006

N-glucuronidation of the platelet-derived growth factor receptor tyrosine kinase inhibitor 6,7-(dimethoxy-2,4-dihydroindeno[1,2-C]pyrazol-3-yl)-(3-fluoro-phenyl)-amine by human UDP-glucuronosyltransferases.

The potential cancer therapeutic agent, 6,7-(dimethoxy-2, 4-dihydroindeno[1,2-c]pyrazol-3-yl)-(3-fluoro-phenyl)-amine (JNJ-10198409), formed three N-glucuronides that were positively identified by liquid chromatography-tandem mass spectrometry and NMR as N-amine-glucuronide (Glu-A), 1-N-pyrazole-glucuronide (Glu-B), and 2-N-pyrazole-glucuronide (Glu-C). All three N-glucuronides were detected in rat liver microsomes, whereas only Glu-A and -B were found in monkey and human liver microsomes. In contrast to common glucuronides, Glu-B was completely resistant to beta-glucuronidase. Kinetic analyses revealed that glucuronidation of JNJ-10198409 in human liver microsomes exhibited atypical kinetics that may be described by a two-site binding model. For the high affinity binding, K(m) values were 1.2 and 5.0 microM, and V(max) values were 2002 and 2,403 nmol min(-1) mg(-1) for Glu-A and Glu-B, respectively. Kinetic constants of low affinity binding were not determined due to low solubility of the drug. Among the human UDP-glucuronosyltransferases (UGTs) tested, UGT1A9, 1A8, 1A7, and 1A4 were the most active isozymes to produce Glu-A; for the formation of Glu-B, UGT1A9 was the most active enzyme, followed by UGT1A3, 1A7, and 1A4. Glucuronidation of JNJ-10198409 by those UGT1A enzymes followed classic Michaelis-Menten kinetics. In contrast, no glucuronides were formed by all UGT2B isozymes tested, including UGT2B4, 2B7, 2B15, and 2B17. Collectively, these results suggested that glucuronidation of JNJ-10198409 in human liver microsomes is catalyzed by multiple UGT1A enzymes. Since UGT1A enzymes are widely expressed in various tissues, it is anticipated that both hepatic and extrahepatic glucuronidation will likely contribute to the elimination of the drug in humans. Additionally, conjugation at the nitrogens of the pyrazole ring represents a new structural moiety for UGT1A-mediated reactions.

Animals↗
PubMed2004

Cytotoxic activities of Coriolus versicolor (Yunzhi) extract on human leukemia and lymphoma cells by induction of apoptosis.

Coriolus versicolor (CV), also known as Yunzhi, is one of the commonly used Chinese medicinal herbs. Although recent studies have demonstrated its antitumour activities on cancer cells in vitro and in vivo, the exact mechanism is not fully elucidated. Hence, the objective of this study was to examine the in vitro cytotoxic activities of a standardized aqueous ethanol extract prepared from Coriolus versicolor on a B-cell lymphoma (Raji) and two human promyelocytic leukemia (HL-60, NB-4) cell lines using a MTT cytotoxicity assay, and to test whether the mechanism involves induction of apoptosis. Cell death ELISA was employed to quantify the nucleosome production resulting from nuclear DNA fragmentation during apoptosis. The present results demonstrated that CV extract at 50 to 800 microg/ml dose-dependently suppressed the proliferation of Raji, NB-4, and HL-60 cells by more than 90% (p < 0.01), with ascending order of IC50 values: HL-60 (147.3 +/- 15.2 microg/ml), Raji (253.8 +/- 60.7 microg/ml) and NB-4 (269.3 +/- 12.4 microg/ml). The extract however did not exert any significant cytotoxic effect on normal liver cell line WRL (IC50 > 800 microg/ml) when compared with a chemotherapeutic anticancer drug, mitomycin C (MMC), confirming the tumour-selective cytotoxicity. Nucleosome productions in HL-60, NB-4 and Raji cells were significantly increased by 3.6-, 3.6- and 5.6-fold respectively upon the treatment of CV extract, while no significant nucleosome production was detected in extract-treated WRL cells. The CV extract was found to selectively and dose-dependently inhibit the proliferation of lymphoma and leukemic cells possibly via an apoptosis-dependent pathway.

Antineoplastic Agents↗
PubMed2004

Differential effect of Coriolus versicolor (Yunzhi) extract on cytokine production by murine lymphocytes in vitro.

Being one of the commonly used Chinese medicinal herbs, Coriolus versicolor (CV), also named as Yunzhi, was known to possess both anti-tumor and immunopotentiating activities. The present study aimed to investigate the in vitro immunomodulatory effect of a standardized ethanol-water extract prepared from CV on the proliferation of murine splenic lymphocytes using the MTT assay, and the production of six T helper (Th)-related cytokines using the enzyme-linked immunosorbent assay (ELISA) technique. The results showed that the CV extract significantly augmented the proliferation of murine splenic lymphocytes in a time- and dose-dependent manner, maximally by 2.4-fold. Moreover, the production of two Th1-related cytokines, including interleukin (IL)-2 and IL-12, in culture supernatants from the CV extract-activated lymphocytes was prominently upregulated at 48 and 72 h. Positive correlations were found between the levels of these two cytokines and the MTT-based proliferative response. In contrast, the production of two other Th1-related cytokines, including interferon (IFN)-gamma and IL-18, was significantly augmented only at 24 h, but not at 48 and 72 h. On the other hand, the levels of two Th2-related cytokines such as IL-4 and IL-6 were undetectable in the culture supernatants of lymphocytes treated with the CV extract. The CV extract was suggested to be a lymphocyte mitogen by differentially enhancing the production of Th1-related cytokines.

Animals↗
PubMed2003

Suppressive effect of combination treatment of leflunomide and methotrexate on chemokine expression in patients with rheumatoid arthritis.

To study the immunosuppressive and anti-inflammatory effects of combined leflunomide and methotrexate (MTX) therapy on chemokine expression in patients with rheumatoid arthritis (RA), nine patients were enrolled for the combination therapy for 24 weeks. These patients have been on treatment with MTX 15 mg/week for not less than 3 months before entry to the study. A loading dose of l00 mg/day of leflunomide was given for 3 days, followed by 10 mg/day for the rest of the study period. Plasma concentrations of monocyte chemotactic protein-1 (MCP-1), thymus- and activation-regulated chemokine (TARC), and macrophage-derived chemokine (MDC) were assayed before and after combination treatment by ELISA. Gene expression of inflammatory cytokines and chemokines of peripheral blood mononuclear cells was analysed by cDNA expression array. Plasma MCP-1, TARC and MDC concentrations were significantly lower in patients after combination treatment [median (interquartile range) before versus after treatment: MCP-1 of 118.0 (64.0-515.2) versus 3.2 (0.0-22.8) pg/ml, P < 0.01; TARC of 126.1 (27.2-197.4) versus 0.0 (0.0-52.5) pg/ml, P < 0.05; MDC of 503.3 (446.2-600.9) versus 366.8 (337.4-393.4) pg/ml, P < 0.05]. Positive correlations among reductions in plasma chemokines and clinical outcome measures were also found. Expression of chemokine genes including MDC and TARC was suppressed after combination treatment [% suppression of 38.7 (54.3-13.0) and 53.7 (55.9-28.4), respectively]. Combination therapy with leflunomide and MTX exhibits anti-inflammatory activity in the suppression of chemokine expression and subsequent recruitment of inflammatory cells into the inflammatory sites in RA.

Adult↗
PubMed2003

Elevated plasma concentrations of nitric oxide, soluble thrombomodulin and soluble vascular cell adhesion molecule-1 in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the correlations among plasma concentrations of nitric oxide (NO), soluble thrombomodulin (sTM) and vascular cell adhesion molecule (sVCAM-1), and whether these three molecules are associated with renal involvement in patients with systemic lupus erythematosus (SLE). METHODS: Plasma NO concentrations of 73 SLE patients (35 with renal disease, RSLE patients; 38 without renal disease, SLE patients) and 28 age- and sex-matched healthy control subjects were measured by the non-enzymatic Griess assay, and sTM and sVCAM-1 by enzyme-linked immunosorbent assay. RESULTS: In RSLE patients, plasma nitrite concentrations were significantly higher than in control subjects (P=0.009) and correlated positively with plasma sTM, plasma creatinine and urea (all P<0.05). Plasma sTM and sVCAM-1 concentrations were significantly elevated in RSLE and SLE patients (both P<0.0001) compared with controls. Plasma sTM was significantly correlated with plasma sVCAM-1, and both were correlated with plasma creatinine and urea and the SLE Disease Activity Index (all P<0.05). CONCLUSION: Elevated plasma NO, sTM, and sVCAM-1 concentrations have significant intercorrelations and are strongly associated with renal involvement in SLE.

Adult↗
PubMed2002

Effects of ionization in single-bubble sonoluminescence.

We studied the effects of ionization in a sonoluminescing (SL) bubble within the hydrodynamic framework. The thermodynamic variables and the degrees of ionization inside the bubble throughout an oscillation cycle are obtained by solving the hydrodynamic equations assuming spherical symmetry. Several models are used to compute the emitted radiation, which are then compared with experimental data. Numerical results show that shock waves are absent in the stable SL regime, and compressional waves are already strong enough to produce moderate temperature and ionization. The degrees of ionization at the bubble center are found to be within 7% to 30%, and Ar+ is the only dominant ion. Moreover, an opacity-corrected blackbody radiation model gives the peak power, pulse widths, and spectra that agree very well with the experimental data.

Journal Article↗
PubMed2002

Elevated production of interleukin-18 is associated with renal disease in patients with systemic lupus erythematosus.

To investigate the production mechanism and proinflammatory role of the cytokine interleukin (IL-18) in lupus nephritis, we investigated the plasma concentrations of IL-18 and nitric oxide (NO) and the release of IL-18 and NO from mitogen-activated peripheral blood monomuclear cells (PBMC), in 35 SLE patients with renal disease (RSLE), 37 patients without renal disease (SLE) and 28 sex- and age-matched healthy control subjects (NC). IL-18 and NO concentrations were measured by ELISA and colourimetric non-enzymatic assay, respectively. Gene expressions of IL-18 and IL-18 receptor were analysed by RT-PCR. Plasma IL-18 and NO concentrations were significantly higher in RSLE than NC (both P < 0.01). Elevation of plasma IL-18 in RSLE correlated positively and significantly with SLE -disease activity index and plasma NO concentration (r = 0.623, P < 0.0001 and r = 0.455, P = 0.017, respectively), and the latter also showed a positive and significant correlation with plasma creatinine (r = 0.410, P = 0.034) and urea (r = 0.685, P < 0.0001). There was no significant difference in gene expressions of IL-18 and IL-18 receptor in PBMC among RSLE, SLE and NC. Percentage increase in culture supernatant IL-18 concentration was significantly higher in RSLE than SLE and NC (both P < 0.05). The basal NO release was significantly higher in RSLE than that in SLE and NC (both P < 0.005). IL-18 is therefore suggested to play a crucial role in the inflammatory processes of renal disease in SLE.

Adult↗
PubMed2001

Evolution of anti-HIV drug candidates. Part 2: Diaryltriazine (DATA) analogues.

A synthesis program directed toward improving the stability of imidoyl thiourea based non-nucleoside reverse transcriptase inhibitors (NNRTIs) led to the discovery of diaryltriazines (DATAs), a new class of potent NNRTIs. The synthesis and anti-HIV structure-activity relationship (SAR) studies of a series of DATA derivatives are described.

Anti-HIV Agents↗
PubMed2001

Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues.

The synthesis and anti-HIV-1 activity of a series of diarylpyrimidines (DAPYs) are described. Several members of this novel class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) are extremely potent against both wild-type and a panel of clinically significant single- and double-mutant strains of HIV-1.

Anti-HIV Agents↗
PubMed2001

Alleviation of wood smoke-induced lung injury by tachykinin receptor antagonist and hydroxyl radical scavenger in guinea pigs.

We recently reported that wood smoke inhalation initially (within 5 min) causes airway injury and subsequently produces both airway and parenchymal injury after a delay (within 2 h). In this study, we investigated the mediator mechanisms of this delayed smoke-induced lung injury in 126 anesthetized and artificially ventilated guinea pigs who received challenges of either air or 40 tidal breaths of wood smoke. Two hours after inhalation, wood smoke produced various injurious responses, including increases in alveolar-capillary permeability, microvascular permeabilities, and histological injury scores, in airway and parenchymal tissues. Pre-treatment given before smoke challenge with CP-96,345 [a tachykinin NK1 receptor antagonist; (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-aza bicyclo(2.2.2.)-octan-3-amine], dimethylthiourea (a hydroxyl radical scavenger), or a combination of these two drugs largely alleviated both the airway and parenchymal responses, whereas pre-treatment with SR-48,968 [a tachykinin NK2 receptor antagonist; (S)-N-methyl-N(4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-butyl)benzamide] or a combination of CP-96,344 and SR-48,965 (inactive enantiomers) failed to do so. Post-treatment given at 5 min after smoke challenge with CP-96,345 or dimethylthiourea significantly alleviated the parenchymal responses, while having no effect on the airway responses. Pre-treatment with dimethylthiourea prevented the smoke-induced reduction in airway neutral endopeptidase activity (an enzyme for tachykinin degradation). We concluded that (1) tachykinins and hydroxyl radical play important roles in producing smoke-induced delayed lung injury in guinea pigs, and both may be involved in the spread of injury from the airways to the pulmonary parenchyma, and (2) the contribution of tachykinins is mediated via the activation of tachykinin NK1 receptors, and is associated with the hydroxyl radical-induced inactivation of airway neutral endopeptidase.

Animals↗
PubMed2001

Asymmetric epoxidation of olefins catalyzed by chiral iminium salts generated in situ from amines and aldehydes.

[reaction: see text] A new approach for catalytic asymmetric epoxidation of olefins was developed that utilized chiral iminium salts, generated in situ from chiral amines and aldehydes, as catalysts. Epoxidation reactions can be conducted with 20 mol % of amines and aldehydes. The enantioselectivity of epoxides can be up to 65%. This modular approach obviates the difficulties inherent in the preparation and isolation of unstable exocyclic iminium salts.

Journal Article↗
PubMed2001

Role of gas density in the stability of single-bubble sonoluminescence.

Recent full hydrodynamic simulations of a sonoluminescing bubble interior have shown that the bubble content is compressed to a very dense state during the violent collapse. In this paper, we numerically studied the shape stability of a radially oscillating gas bubble by using Hilgenfeldt et al. theoretical model with corrections taking into account the gas density effect. Our results show that gas density variations not only significantly suppress the Rayleigh-Taylor instability, but also enhance the threshold of the parametric instability under sonoluminescence conditions.

Journal Article↗
PubMed2001

Sensitivity of vagal afferent endings to chemical irritants in the rat lung.

This study was carried out to investigate the relationship between the conduction velocity of the vagal afferents arising from the rat lungs and their sensitivities to capsaicin, other chemical irritants, and lung inflation. We recorded single-unit activities of vagal pulmonary afferents (n = 205) in anesthetized, open-chest rats, and distinguished C fibers (conduction velocity < 2 m/sec) from myelinated afferents; the latter group was further classified into rapidly adapting pulmonary receptors (RARs) and slowly adapting pulmonary stretch receptors (SARs) on the basis of their adaptation indexes to lung inflation. Right-atrial injection of capsaicin (1 microg/kg) evoked an abrupt and intense stimulatory effect in 88.9% (64/72) of the pulmonary C fibers tested, but only a mild stimulation in 6.3% (3/48) of the RARs and none of the SARs. Other inhaled and injected chemical stimulants (e.g., cigarette smoke, lactic acid) activated 68.9% (42/61) of the pulmonary C fibers. The same chemical irritants exerted a mild stimulatory effect in only 14.5% (8/55) of the RARs; this subgroup of RARs exhibited a low or no baseline activity, and half of them were located near the hilum. Chemical stimulants had little or no effect on SARs. The response of pulmonary C fibers to lung inflation (tracheal pressure = 30 cm H2O) was not only extremely weak, but also showed a longer onset latency and an irregular pattern. In a sharp contrast, lung inflation evoked rapid and vigorous discharges in both RARs and SARs. In conclusion, C fibers are the primary type of chemosensitive vagal pulmonary afferents in rat lungs.

Animals↗
PubMed2001

Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma.

Allergen-reactive T helper type-2 (Th2) cells and proinflammatory cytokines have been suggested to play an important role in the induction and maintenance of the inflammatory cascade in allergic asthma. We compared the plasma concentrations of novel proinflammatory cytokines IL-17 and IL-18, other proinflammatory cytokines IL-6 and IL-12, Th2 cytokines IL-10 and IL-13, and intracellular interferon-gamma (IFN-gamma) and IL-4 in Th cells of 41 allergic asthmatics and 30 sex- and age-matched health control subjects. Plasma cytokines were measured by enzyme-linked immunosorbent assay. Intracellular cytokines were quantified by flow cytometry. Plasma IL-18, IL-12, IL-10, IL-13 concentrations were significantly higher in allergic asthmatic patients than normal control subjects (IL-18: median 228.35 versus 138.72 pg/ml, P < 0.001; IL-12: 0.00 versus 0.00 pg/ml, P = 0.001; IL-10: 2.51 versus 0.05 pg/ml, P < 0.034; IL-13: 119.38 versus 17.89 pg/ml, P < 0.001). Allergic asthmatic patients showed higher plasma IL-17 and IL-6 concentrations than normal controls (22.40 versus 11.86 pg/ml and 3.42 versus 0.61 pg/ml, respectively), although the differences were not statistically significant (P = 0.077 and 0.053, respectively). The percentage of IFN-gamma-producing Th cells was significantly higher in normal control subjects than asthmatic patients (23.46 versus 5.72%, P < 0.001) but the percentage of IL-4 producing Th cells did not differ (0.72 versus 0.79%, P > 0.05). Consequently, the Th1/Th2 cell ratio was significantly higher in normal subjects than asthmatic patients (29.6 versus 8.38%, P < 0.001). We propose that allergic asthma is characterized by an elevation of both proinflammatory and Th2 cytokines. The significantly lower ratio of Th1/Th2 cells confirms a predominance of Th2 cells response in allergic asthma.

Adult↗
PubMed2001

Effects of dexamethasone on the expression of Fas molecules and apoptosis of lymphocytes in patients with systemic lupus erythematosus.

Previous studies have shown that the autoimmune phenomenon could be caused by defective apoptosis of autoreactive lymphocytes. Corticosteroids used for treatment of systemic lupus erythematosus (SLE) are potent apoptosis inducers. We examined dexamethasone (DEX)-induced apoptosis and Fas expression in peripheral blood lymphocytes of SLE patients and normal subjects. Peripheral blood lymphocytes were obtained from 40 SLE patients and 18 sex- and age-matched control subjects. Percentages of apoptosis and expression of Fas molecule in lymphocytes were assessed by flow cytometry. Fas expression in lymphocytes treated with or without DEX was significantly higher in SLE patients than normal controls [median (interquartile range) of mean fluorescence intensity without DEX: 74.9 (50.7-98.0) vs 20.0 (17.7-25.0), p < 0.001; with DEX: 77.9 (56.0-130.5) vs 20.5 (18.6-24.7), p<0.001]. DEX (0.1-5 microM) could also induce apoptosis of lymphocytes from SLE and control subjects in a dose-dependent manner. Elevation of apoptotic susceptibility was more prominent in DEX-treated SLE lymphocytes [33.9% (24.7-37.5%) vs 19.6% (13.6-26.1 %), p = 0.003]. The higher apoptotic susceptibility of SLE lymphocytes upon DEX treatment in vitro may be related, at least partly, to the pharmacological action of corticosteroids.

Adolescent↗
PubMed2001

Malignant melanoma of the eustachian tube.

The case report describes the diagnosis and the management of malignant melanoma of the eustachian tube. This is an exceedingly rare condition that was treated with endoscopic surgery and post-operative radiotherapy. During a 15-month follow-up, there was no evidence of recurrence.

Ear Neoplasms↗
PubMed2000

Homozygous mutation in cardiac troponin T: implications for hypertrophic cardiomyopathy.

BACKGROUND: Mutations in the gene that encode cardiac troponin T (cTnT) account for approximately 15% of cases of familial hypertrophic cardiomyopathy (HCM). These mutations are associated with a particularly severe form of HCM characterized by a high incidence of sudden death and a poor overall prognosis, despite subclinical or mild left ventricular hypertrophy. METHODS AND RESULTS: We evaluated a family with HCM and multiple occurrences of sudden death in children. DNA samples were isolated from peripheral blood or paraffin-embedded tissue, and all protein-encoding exons of the cTnT gene were sequenced. A mutation was identified in exon 11 and is predicted to substitute a phenylalanine-for-serine mutation at residue 179 (Ser(179)Phe) in cTnT. Both parents and 3 of 4 surviving and clinically unaffected children were heterozygous for this mutation; another clinically unaffected child did not carry the mutation. Genetic analysis of DNA from a child who died suddenly at age 17 years demonstrated he was homozygous for this mutation. A review of his echocardiogram revealed profound left and right ventricular hypertrophy. CONCLUSIONS: An homozygous Ser(179)Phe mutation in cTnT causes a severe form of HCM characterized by striking morphological abnormalities and juvenile lethality. In contrast, the natural history of the heterozygous mutation is benign. These studies emphasize the relevance of genetic diagnosis in hypertrophic cardiomyopathy and provide a new perspective on the clinical consequences of troponin T mutations.

Adolescent↗