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Biomedical subjects

F Cheng

Publications and source records attributed to F Cheng.

At least 19 recordsLinked to original sources

Longer term follow up of aerobic capacity in children affected by severe acute respiratory syndrome (SARS).

BACKGROUND: A study was undertaken to investigate the aerobic capacity and pulmonary function of children 6 and 15 months after the diagnosis of severe acute respiratory syndrome (SARS). METHODS: Thirty four patients of mean age 14.7 years completed both pulmonary function and maximal aerobic capacity tests at 6 months. All had normal clinical examination and were asymptomatic. Their exercise responses were compared with a group of healthy controls. Complete data were collected on 27 of the original 34 cases at 15 months. RESULTS: Compared with normal controls, the patient group had significantly lower absolute and mass related peak oxygen consumption (peak V o(2) (p<0.01)), higher ventilatory equivalent for oxygen (p<0.01), lower oxygen pulse (p<0.01), and a lower oxygen uptake efficiency slope (p<0.01) at 6 months. This impairment was unexpected and out of proportion with the degree of lung function abnormality. Residual high resolution computed tomography of thorax (HRCT) abnormalities were present in 14 patients. Those with abnormal HRCT findings had significantly lower mass related peak V o(2) than subjects with normal radiology (p<0.01). Absolute and mass related peak V o(2) in the patient group remained impaired at 15 months despite normalisation of lung function in all patients. CONCLUSIONS: The mechanism for the reduced aerobic capacity in children following SARS is not fully understood, but it is probably a consequence of impaired perfusion to the lungs at peak exercise and deconditioning.

Adolescent↗

The effect of renal ischemia-reperfusion injury on expression of RAE-1 and H60 in mice kidney.

INTRODUCTION: NKG2D, an activating receptor, may trigger NK and CD8+ T cells. Ligands for NKG2D and major histocompability complex class I chain-related antigen (MIC) have been reported to be expressed in rejected human renal allografts. MIC-NKG2D engagement may induce natural killer (NK) cell activation providing T-cell costimulation. We hypothesized that this interaction between innate and adaptive immunity may occur during kidney ischemia-reperfusion injury (IRI). METHODS: Male C57BL/6 mice after right renal resection were subjected to 35 minutes of left renal ischemia: the ischemic group. Sham-operated mice underwent the same protocol without vascular occlusion. The sham and ischemic kidneys were removed at 2 to 7, 10, 14, or 28 days postoperatively. The normal, sham, and ischemic kidney tissues were collected for reverse-transcriptase polymerase chain reaction, and immunohistochemistry analysis of MIC homologues in mice (Rae-1 and H60). RESULTS: Compared with no expression in sham control and normal kidneys, IRI caused mRNA expression of Rae-1 from 2 to 10 days postoperatively and protein expression of Rae-1 from 2 to 14 days postoperatively in ischemic kidneys. We observed no expression of H60 mRNA or protein in any kidney. CONCLUSION: H60 transcripts have been reported to be present in the BALB/c background but not in C57BL/6. We found IRI did not cause H60 mRNA on protein expression in C57BL/6 kidneys. Rae-1 was absent in normal C57BL/6 kidneys. The IRI-induced expression of the NKG2D ligand, Rae-1, might activate NK and CD8+ T cells. Our results suggested that MIC may be an important link between innate and adaptive immunity in kidney IRI.

Animals↗

Hypoxia/reoxygenation up-regulated the expression of death receptor 5 and enhanced apoptosis in human hepatocyte line.

OBJECTIVES: Ischemia-reperfusion injury (IRI) is a key factor that contributes to early and late dysfunction of liver graft. Although we have known that hepatocytes express death receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), the effects of TRAIL on hypoxia/reoxygenation (H/R)-mediated apoptosis are unclear. This study sought to examine the effects of H/R on TRAIL cytotoxicity, as a cause of primary hepatic graft dysfunction, delayed graft refunction, and chronic graft dysfunction. METHODS: Using an hepatocyte H/R model in vitro to mimic IRI in the grafted liver, normal human hepatocytes HL-7702 were exposed to hypoxia for 5 hours then reoxygenated for 0, 2, 4, 6, or 20 hours. In another experiment, hepatocytes were exposed to hypoxia for 0, 2, 4, 8, or 20 hours. Expressions of TRAIL-R2/Death receptor 5 (DR5) mRNA were measured by semiquantitative reverse-transcriptase polymerase chain reactions. After 16 hours of hypoxia, human hepatocytes were treated with TRAIL in different concentrations for 5 hours. The death of hepatocytes was confirmed by flow cytometer and methyl thiazolyl tetrazolium analysis. RESULT: After 5-hour hypoxia, the expressions of DR5 mRNA increased at all times of reoxygenation. DR5 mRNA was up-regulated from 0 hour after reoxygenation, reaching a peak value at 2 hours after reoxygenation compared with the normoxia cultured cells. Moreover, DR5 mRNA was up-regulated gradually following prolonged hypoxia. TRAIL-mediated cell killing was concentration-dependent being greater in the hypoxia treatment group compared to the normoxia group. CONCLUSIONS: H/R up-regulated the expression of DR5 and enhanced TRAIL-mediated apoptosis in an human hepatocyte line. The TRAIL pathway might play a critical role in hepatocyte apoptosis induced by IRI.

Apoptosis↗

Effect of cyclosporine on expression of MIC in human hepatocytes.

OBJECTIVES: The human major histocompatibility complex class I chain-related antigen A, B (MICA, B) are believed to be "cell stress sensors," which encode stress-inducible surface proteins that bind to NKG2D, an activating receptor of NK, alpha beta and gamma delta T cells. While cyclosporine (CsA) has improved patient and graft survival rates following solid organ transplantation, its clinical use is often limited by acute and chronic toxicity. Besides ischemia-reperfusion injury, which could up-regulate the expression of MIC, the toxicity of CsA may also be another violent stress factor. The purpose of this study was to investigate whether CsA can affect the expression of MIC. METHODS: Various doses of CsA (5 or 20 microg/mL) was added to cultured human hepatocytes for 1, 3, 5, 8, or 24 hours. The expression of MIC was measured by immunofluorescence using a laser scanning confocal microscope. RESULTS: CsA (5 or 20 microg/mL) upregulated MIC protein expression in hepatocytes at 1 hour, peaking at 3 hours, and persisting until 5 hours (P < .05), returning to normal levels after 8 to 24 hours (P > .05). CONCLUSION: This study reported that CsA up-regulated MIC expression on human hepatocytes. MIC, as a "cellular stress biomarker," may play a significant role in activating NK, T, and B lymphocyte responses associated with transplantation. This study suggested that immunosuppressants produce deterioration in organ function in transplantation.

Cells, Cultured↗

Yisheng injection decreases the expression of H60 and RAE-1 genes in ischemic mice liver.

OBJECTIVE: Major histocompatability complex class I chain-related antigen A, B (MICA, B) functions as ligands for human NKG2D receptors, which may play a role in graft rejection and cellular stress. In this study we explored the effect of ischemia/reperfusion injury (IRI) on the expression of H60 and RAE-1 (MICA, B homologues) in mice to study the protective effect of Yisheng injection (YS), an herbal preparation developed from traditional Chinese medicine. METHODS: Male BALB/c mice were divided into sham, ischemic, and YS-treated groups using 90 minutes of left liver lobe ischemia. Sham control mice underwent the same operation, but without vascular occlusion. In the treated group, YS (20 mg/kg) was given before ischemia and after reperfusion for 7 days. Liver samples collected at 7 days postoperation were used for real-time quantitative polymerase chain reaction analysis, Western blotting, and immunohistochemical assays. RESULTS: Compared with the sham group, H60 and RAE-1 mRNA levels were increased by sevenfold and 4.5-fold in the ischemic group, respectively. After YS treatment, they were reduced by 76% and 70%, respectively. Western blotting and immunohistochemical assays showed that there was absent or faint H60 and RAE-1 expression in sham liver, but they were apparently increased in ischemic liver; however, the expressions were significantly decreased in the presence of YS. CONCLUSIONS: Hepatic IRI significantly increased H60 and RAE-1 expression in mouse liver. YS treatment effectively reduced this increase, seeming to attenuate NKG2D-ligand-mediated immune responses caused by IRI. This may suggest a new concept to prevent IRI and graft rejection.

Animals↗

Dexamethasone in the treatment of obstetric cholestasis: a case series.

Twelve women with obstetric cholestasis were given dexamethasone after failure to respond to ursodeoxycholic acid. Clinical improvement was achieved in eight cases, without complete resolution of symptoms. Biochemical response was achieved in seven cases. All but two cases had good correlation between clinical and biochemical response. Women of Asian and South American origin were more likely to respond to dexamethasone than Caucasians. There were no reported maternal or fetal side-effects. However, the subsequent consequences of dexamethasone treatment for the mother and fetus have not been thoroughly evaluated. Therefore, even in Asian and South American women, larger studies of dexamethasone are required before this treatment can be recommended as a universally safe and effective treatment for obstetric cholestasis.

Anti-Inflammatory Agents↗

The relationship between HPV16 and expression of CD44v6, nm23H1 in esophageal squamous cell carcinoma.

The esophageal squamous cell carcinoma (ESCC) has high incidence in Shaanxi Province of China. More and more researches indicated that human papillomavirus type 16 (HPV16) might play an important role in carcinogenesis of ESCC but the relationship between HPV16 and CD44v6, nm23H1 has not been elucidated. HPV16 was detected by amplifying HPV16 E6 gene through polymerase chain reaction (PCR) method and the expression of CD44v6, nm23H1 in 40 ESCCs and fifteen normal esophageal mucosa (NEM) from Shaanxi Province was examined by Streptavidin-Peroxidase (SP) method using monoclonal antibody specific to CD44v6 and nm23H1. The positive rates of HPV16 E6 gene, CD44v6 and nm23H1 were 60% (24/40), 65% (26/40) and 45% (18/40) respectively in ESCCs and 26.67% (4/15), 33.33% (5/15) and 86.67% (13/15) respectively in NEMs. There exited statistical difference for HPV16, CD44v6 and nm23H1 between NEMs and ESCCs respectively (p < 0.05). The relationship between HPV16 and the expression of CD44v6 in ESCCs was statistical significance (P = 0.021), but no significant correlation was found between HPV16 and the expression of nm23H1 (P = 0.436) in ESCCs. The infection rate of HPV16 had no statistical difference in all pathological features we observed, but the expression rates of CD44v6 and nm23H1 had statistical correlation with invasion (p = 0.001, 0.013) and lymph nodes metastasis (p = 0.014, 0.002) respectively. In different histology grade of ESSCs, the relationship between HPV16 and CD44v6 was statistical significance in grade I (p = 0.044) but was not in grade II (p = 0.165) and grade III (p = 0.658), however as to the expression of nm23H1 there exited no statistical significance in all histology grades of ESCC (p > 0.05). The expression rates of CD44v6 and nm23H1 were statistically different between grade I and II (p = 0.004, 0.016) respectively and between grade I and grade III (p = 0.014, 0.020), but not statistically different between grade II and III (p = 0.792, 0.943) respectively. Our data firstly suggested that there existed the statistical relationship between the infection of HPV16 and the expression of CD44v6 in ESCCs and that HPV16 may be involved in invasion and metastasis of ESCC.

Carcinoma, Squamous Cell↗

ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) affects approximately 0.7% of pregnancies in the UK and is associated with prematurity, fetal distress, and intrauterine death. Homozygous mutations in the ATP8B1 gene cause cholestasis with a normal serum gamma-glutamyl transpeptidase (gamma-GT), and have been reported in two forms of cholestasis: progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis (BRIC). AIMS: To establish whether mutations in ATP8B1 are associated with ICP in British cases PATIENTS: Sixteen well phenotyped women with ICP without raised gamma-GT were selected for sequence analysis. Subsequently, 182 patients and 120 controls were examined for the presence of the variants detected. METHODS: All coding exons were sequenced in 16 cases. Eight ICP cases, including two women carrying a mutation, were investigated using in vivo hepatic (31)P magnetic resonance spectroscopy (MRS) RESULTS: Two heterozygous ATP8B1 transitions (208G>A and 2599C>T) that resulted in amino acid substitutions were identified; 208G>A was identified in three cases. MRS revealed an increased phosphodiester signal (Mann-Whitney U test, p = 0.03) and a decreased phosphomonoester/phosphodiester ratio (p = 0.04) in ICP cases compared with controls. CONCLUSIONS: We were able to demonstrate ATP8B1 mutations in ICP. MRS studies suggest that susceptibility to ICP is associated with a relative rise in biliary phospholipid. These data also suggest that MRS may be used for non-invasive assessment of the liver and biliary constituents in cholestasis.

Adenosine Triphosphatases↗

Novel aspects of glypican glycobiology.

Mutations in glypican genes cause dysmorphic and overgrowth syndromes in men and mice, abnormal development in flies and worms, and defective gastrulation in zebrafish and ascidians. All glypican core proteins share a characteristic pattern of 14 conserved cysteine residues. Upstream from the C-terminal membrane anchorage are 3-4 heparan sulfate attachment sites. Cysteines in glypican-1 can become nitrosylated by nitric oxide in a copper-dependent reaction. When glypican-1 is exposed to ascorbate, nitric oxide is released and participates in deaminative cleavage of heparan sulfate at sites where the glucosamines have a free amino group. This process takes place while glypican-1 recycles via a nonclassical, caveolin-1-associated route. Glypicans are involved in growth factor signalling and transport, e.g. of polyamines. Cargo can be unloaded from heparan sulfate by nitric oxide-dependent degradation. How glypican and its degradation products and the cargo exit from the recycling route is an enigma.

Animals↗

Eighteen living related liver transplants for Wilson's disease: a single-center.

The aim of this study was to review our experience with living related liver transplantation (LRLT) for Wilson's disease. From January 2001 to July 2003 LRLT were performed in 18 patients with Wilson's disease, seven of whom had neurologic complications. The mean age of the patients was 13.5 +/- 2.3 years (range 6 to 20). Before transplantation all recipients displayed low serum ceruloplasmin levels (mean value = 118.4 +/- 32.6 mg/L). The serum ceruloplasmin levels increased to an average of 236.8 +/- 38.5 mg/L after LRLT at the latest evaluation, which ranged between 2 and 32 months after transplantation. A marked reduction in urinary copper excretion was observed in all recipients after transplantation. All recipients are alive and remain well. None have developed signs of recurrent Wilson's disease after a mean follow-up of 18.2 +/- 9.4 months (range 2 to 32 months). The donors were 17 mothers and one father of mean age 34.0 +/- 3.0 years (range 30 to 45 years). The serum ceruloplasmin levels were within normal limits in all donors (mean 226 +/- 27.8 mg/L). Two donors had biliary leakage and percutaneous drainage Grafts included four right lobes without the hepatic middle vein and 14 left lobe grafts with the middle vein. LRLT is a curative procedure for Wilson's disease presenting with fulminant hepatic failure and the others with end-stage hepatic insufficiency. After liver transplantation, the serum ceruloplasmin level increases to the normal range, urinary copper excretion decreases, and neurological manifestations improve to various extents.

Adolescent↗

Effect of ligustrazine on ischemia-reperfusion injury in murine kidney.

INTRODUCTION: Ischemia-reperfusion (I/R) injury is unavoidable in cadaveric renal transplantation. It contributes to acute rejection and chronic allograft dysfunction. Studies have shown that Ligustrazine, a purified and chemically identified component of a Chinese herbal remedy, is a potent blocker of vasoconstriction and has strong effects to scavenge oxygen free radicals. Since warm I/R is potentially more damaging than cold storage, we investigated the possible protective effect of Ligustrazine on warm I/R in mice. METHODS: Unilaterally nephrectomized C57BL/6 male mice were subjected to 50 minutes of left renal ischemia. Group I were sham-operated animals; group II, nontreated animals (saline, iP 30 minutes before I/R); and group III, Ligustrazine-treated animals (80 mg/kg, iP 30 minutes before I/R). Mice were sacrificed 24 hours postreperfusion. Serum creatinine, blood urea nitrogen, kidney malondialdehyde (MDA)level, and superoxide dismutase (SOD) were determined as well as examining the kidneys histologically with immunohistochemistry for Bcl-2, and ICAM-1. RESULTS: I/R produced a six fold increase in creatinine and urea nitrogen levels in group II. Ligustrazine halved the increase, as well as attenuated the necrosis and apoptosis in the tubules (P < .01). Ligustrazine decreased MDA levels and ameliorated the down-regulation of SOD activity. Bcl-2 was up-regulated following I/R, especially in the Ligustrazine-treated group (P < .01). The up-regulation of ICAM-1 was greatly diminished by Ligustrazine (P < .01). CONCLUSION: These findings suggest that Ligustrazine reduces the renal dysfunction associated with warm I/R of the kidney.

Animals↗

Alleviating ischemia-reperfusion injury in aged rat liver by induction of heme oxygenase-1.

BACKGROUND: Heme oxygenase-1 (HO-1), a cytoprotective protein, may be important in ameliorating hepatic ischemia-reperfusion (I/R) injury, a critical factor in the dysfunction of the aged liver after transplantation. METHODS: We used hemin to overexpress HO-1 and analyze its effects in a model of I/R in aged livers used for orthotopic transplantation. RESULTS: The SGOT levels in the hemin group were significantly lower than those of the saline treatment group. Hemin liver grafts showed markedly fewer apoptotic (TUNEL+) liver cells after reperfusion compared with the controls. The plasma nitric oxide levels in the hemin group were significantly lower than those in the control group. Unlike untreated or hemin + Znpp-treated orthotopic liver transplant controls, iNOS expression in the hemin group was almost absent at 12 and 24 hours, after reperfusion. In contrast, eNOS was comparable in hemin and saline orthotopic liver transplants. The increased levels of Bcl-2 expression compared with saline controls were most pronounced at 12 hours after transplantation. In contrast, caspase 3 was lower at 24 hours among the hemin-pretreated group compared with saline-treated liver transplant controls. CONCLUSIONS: HO-1 alleviated the I/R injury in the aged liver by suppressing local expression of inducible nitric oxide synthase and by modulating pro- and antiapoptotic pathways.

Aging↗

Rapid induction of cAMP/PKA pathway during retinoic acid-induced acute promyelocytic leukemia cell differentiation.

The second messenger cyclic adenosine monophosphate (cAMP) plays an important role in cell proliferation, differentiation and apoptosis. In the present work, we evaluated the cAMP signaling in acute promyelocytic leukemia (APL) cells in the context of differentiation induced by all-trans retinoic acid (ATRA). There was a marked increase in the intracellular cAMP level within a few minutes after treatment with ATRA in APL cell line NB4 and fresh APL cells, whereas no such phenomenon was observed in NB4-R1 cells that are resistant to ATRA-induced maturation. In addition, the basal level of intracellular cAMP was lower in NB4-R1 than in NB4 cells. Mechanistic study showed that this induction of cAMP was mediated through the activation of adenylate cyclase. Moreover, we found that cAMP-dependent protein kinase (PKA) activity was quickly upregulated in parallel in ATRA-treated NB4 cells, and the phosphorylation of RARalpha by PKA could increase its transactivation effect. Use of H-89, an inhibitor of PKA, could partially suppress the transcriptional expression of ATRA target genes and ATRA-induced differentiation of APL cells. Taken together, we suggested a crosstalk between ATRA-induced cytosolic pathway and nuclear pathway in APL cell differentiation.

Adenylyl Cyclases↗

Factors affecting uptake of cervical and breast cancer screening among perimenopausal women in Hong Kong.

OBJECTIVES: To identify factors affecting cervical and breast cancer screening attendance among women aged 44 to 55 years by comparing self-reported uptake of cervical smear and clinical breast examination between patients and a population sample. DESIGN AND SETTING: Telephone survey and audit of clinic records to confirm patients' self-report. PARTICIPANTS: Two thousand and sixty-seven women identified through random telephone dialling from the residence directory and 319 patients ever-registered at a family practice teaching clinic. MAIN OUTCOME MEASURES: Uptake of cervical smear and clinical breast examination. RESULTS: The proportion of women undergoing cervical smear tests and clinical breast examination in the previous 12 months were 35.4% and 22.6%, respectively, for randomly selected women, while the figures were 47.2% and 50.6%, respectively, for patients. Record audit confirmed high rates of screening for patients according to evidence-based protocols (85.1% had had a cervical smear within 3 years). For women in the random sample (mean age, 48.9 years; standard deviation, 3.3 years), those who were older, postmenopausal, not receiving hormone therapy, educated to primary level, and with no chronic diseases were least likely to have had screening. For clinic patients (mean age, 47.9 years; standard deviation, 2.8 years), lower education level was the only variable associated with no recent smears. CONCLUSIONS: Healthy perimenopausal and postmenopausal women in the community with lower educational level and not receiving hormone therapy were more likely to be underscreened. Attendance of 44- to 55-year-old women at a family medicine clinic that actively promotes preventive medicine was associated with high screening uptake.

Adult↗

Novel C60-based building blocks derived from C60(2-) anion.

[reaction: see text]. Reactions of chemically generated C60(2-) dianion with halo derivatives bearing a second functional group (halo, ester, ketone) give rise to new organo C60 derivatives. Thus, the regioselective formation of 1,2- and 1,4-adducts is observed from long-chain halo derivatives, whereas using 1,3-dihaloalkanes leads to 1,2-fused ring C60 adducts. Such adducts may be used as new synthons in C60 chemistry, thus leading to new C60-based dyads, as exemplified by two examples.

Journal Article↗

Differences in the uptake and nuclear localization of anti-proliferative heparan sulfate between human lung fibroblasts and human lung carcinoma cells.

Heparan sulfate inhibits the proliferation of normal human lung fibroblasts (HFL-1) but not of a human lung carcinoma cell-line (A549). In this study we investigated possible mechanisms and structural requirements by which antiproliferative heparan sulfates exerts its effects on binding, uptake and subcellular localisation. Both HFL-1 and A549 cells were incubated with 125I- or rhodamine-labeled L-iduronate-rich antiproliferative heparan sulfate species as well as L-iduronate-poor inactive ones. The antiproliferative heparan sulfate was bound to the cell surface on both HFL-1 and A549 cells, but to a lesser extent and with less affinity to A549 cells. Both cell types bound the antiproliferative heparan sulfate with one high- and with one low affinity site. The L-iduronate-poor heparan sulfate bound to a lesser extent and with less affinity to both cell types compared to the antiproliferative heparan sulfate. The antiproliferative heparan sulfate accumulated in the cytoplasm of HFL-1 cells after 24 h incubation, but after 72 h it was found evenly distributed in the nucleus. The time-scale for antiproliferative activity correlated with nuclear localization. In contrast, in A549 cells it was only found near the nuclear membrane. The inactive heparan sulfate was taken up in considerably smaller amounts compared to the antiproliferative heparan sulfate and could not be detected in the nucleus of either HFL-1 or A549 cells. Our data suggest that the antiproliferative activity of L-iduronate-rich heparan sulfate on normal fibroblasts may be due to direct effects on nuclear processes, such as gene transcription.

Animals↗

[Tracing algorithms of ECG tracks from scanned image].

This paper presents a discussion on the tracing algorithms of the extraction of Electrocardiogram (ECG) data from scanned image of hardcopy ECG. We have advanced a new algorithm integrated by seek-and-predict method and polygon model method, which can tolerate crossing of two leads, fault-line and disturbing of grid lines. Two practical situations that may be encountered while processing hardcopy ECG are discussed in detail. Furthermore, the after-treatment of extraction-filtering is considered and an SVD-based filter designed to smooth ECG signal is analyzed.

Algorithms↗