Biomedical subjects

Hong Ding

Publications and source records attributed to Hong Ding.

49 records · Page 3Linked to original sources

PubMed2003

In vivo characterization of A-192411: a novel fungicidal lipopeptide (II).

The ability of the novel antifungal cyclic hexalipopetide A-192411 to treat fungal infections in rodents is presented. Efficacy was demonstrated against Candida albicans as both prolonged survival of systemically infected mice and clearance of viable yeasts from kidneys. The efficacy of A-192411, administered intraperitoneally, was equivalent to amphotercin B at a 4-fold lower dose by weight in the systemic candidiasis models in mice, while the efficacy of A-192441 administered intravenously was equivalent to amphotercin B by weight in the Candida pyelonephritis model in rats. A-192411 also slightly prolonged the survival of immunocompromised mice infected systemically with Aspergillus fumigatus.

Amphotericin B↗

PubMed2003

The endothelium in health and disease--a target for therapeutic intervention.

In this review we discuss the contribution of NO, prostacyclin and endothelium-derived relaxing factor--endothelium-derived hyperpolarizing factor, or EDHF, to vascular function. We also explore the hypotheses (1): that tissues can store NO as nitrosothiols (RSNOs) and (2) that such RSNO stores can be modulated by physiological and pathophysiological processes. Notably in the microcirculation, EDHF appears to play an important role in the regulation of vascular tone. Leading candidates for EDHF include extracellular potassium (K+), an epoxygenase product, hydrogen peroxide and/or a contribution from myoendothelial gap junctions. Data from our laboratory indicate that in mouse vessels, different endothelium-dependent vasodilators, such as acetylcholine and protease-activated receptor (PAR) agonists, release different endothelium-derived relaxing factors. The combination of two K-channel toxins, apamin and charybdotoxin, inhibits EDHF activity in most protocols. Endothelial dysfunction is considered as the major risk factor and a very early indicator of cardiovascular disease including the cardiovascular complications of type I & types II diabetes. Impaired endothelium-dependent vasodilatation results primarily from a decreased synthesis of endothelium-derived nitric oxide (NO) and/or an increase in the production of reactive oxygen species such as superoxide. We have shown that the administration of tetrahydrobiopterin, an important co-factor for nitric oxide synthase (NOS) partially restores endothelial function (1) in leptin-deficient mice (db/db) with spontaneous type II diabetes, as well as (2) in human vascular tissue harvested for coronary artery bypass grafting (CABG). These data suggest that a deficiency in the availability of tetrahydrobiopterin plays an important role in vascular dysfunction associated with Type II diabetes. In addition, changes in the contribution of EDHF occur in vascular tissue from the db/db mice suggesting a compensatory increase in EDHF production; whether this alteration in EDHF production is physiological or pathophysiological remains controversial.

Animals↗

PubMed2003

Influence of Kupffer cells on hepatic signal transduction as demonstrated by second messengers and nuclear transcription factors.

AIM: To understand the influence of Kupffer cell (KC) on signal transduction pathways in the liver. METHODS: To decrease selectively the number and function of KC, Kunming mice were ip injected with a single dose of gadolinium chloride (GdCl3, 20 mg x kg(-1)), the time-effect relationship assessment was performed after 1 d, 3 d and 6 d. sALT, sGST, liver glycogen content, phagocytic index, and expression of CD68 were assessed as the indexes of hepatotoxicity and functions of KC respectively, and morphology of KC was observed with transmission electron microscopy. Furthermore, cAMP, PGE2 level, nitric oxide (NO) content, and mRNA expression of NFkappaBp65, Erk1, STAT1 were examined. RESULTS: GdCl3 could selectively cause apoptosis of KC and obvious reduction of KC's activity, but no hepatotoxicity was observed. One day after KC blockade, NO, PGE2, cAMP contents in the liver were reduced 21.0%, 6.94-fold, 8.3%, respectively, and mRNA expression of NFkappaBp65 was decreased 3.0-fold. The change tendency of NO, PGE2, and cAMP contents and mRNA expression of NFkappaBp65 were concomitant with recovery of the functions of KC. The contents of NO, PEG2, cAMP were increased when the functions of KC was recovered. However, all of the changes could not return to the normal level except NO content after 6 d Gdcl3 treatment. No obvious changes were found in STAT1 and Erk1 mRNA expression in the present study. CONCLUSION: Hepatic NO, PGE2, cAMP level and mRNA expression of NFkappaBp65 are closely related with the status of KC. It suggests that KC may play an important role in the cell to cell signal transduction in the liver.

Alanine Transaminase↗

PubMed2003

Modulation of GdCl3 and Angelica sinensis polysaccharides on differentially expressed genes in liver of hepatic immunological injury mice by cDNA microarray.

AIM: To study the modulating effect of GdCl(3) and Angelica Sinensis polysaccharides (ASP) on differentially expressed genes in liver of hepatic immunological mice by cDNA microarray. METHODS: Hepatic immunological injury was induced by lipopolysaccharide (LPS ip, 0.2 mg/kg(-1)) in bacillus calmetteguerin (BCG ip, 1 mg/kg(-1)) primed mice; A single dose of 20 mg/kg(-1) GdCl(3) was simultaneously pretreated and 30 mg/kg(-1) ASP (ig, qdX7 d) was administrated when the BCG+LPS was primed. The mice were sacrificed at the end of the 7(th) day after ip LPS for 6 h and the liver was removed quickly. The PCR products of 512 genes were spotted onto a chemical material-coated glass plate in array. The DNAs were fixed to the glass plate after series of treatments. The total RNAs were isolated from the liver tissue, and were purified to mRNAs by Oligotex. Both mRNAs from the normal liver tissue and the liver tissue from the mice with hepatic immunological injury or that pretreated with GdCl(3) or ASP were reversely transcribed to cDNAs with the incorporation of fluorescent dUTP to prepare the hybridization probes. The mixed probes were hybridized to the cDNA microarray. After high-stringent washing, the cDNA microarray was scanned for fluorescent signals and showed differences between the two tissues. RESULTS: Among the 512 target genes, 18 differed in liver tissue of hepatic immunological injury mice, and 6 differed in those pretreated by ASP, 7 differed in those pretreated by GdCl(3). CONCLUSION: cDNA microarray technique is effective in screening the differentially expressed genes between two different kinds of tissue. Further analysis of those obtained genes will be helpful to understand the molecular mechanism of hepatic immunological injury and to study the intervention of drug. Both ASP and GdCl(3) can decrease the number of the differentially expressed genes in liver tissue of mice with hepatic immunological injury.

Angelica sinensis↗

PubMed2003

Characterization of focal hepatic lesions with contrast-enhanced C-cube gray scale ultrasonography.

AIM: To characterize enhancement patterns of focal hepatic lesions using C-cube gray scale sonography with a microbubble contrast agent and to evaluate its usefulness in differential diagnosis of hepatic lesions. METHODS: Fifty-four patients with 58 focal hepatic lesions were examined with Levovist-enhanced C-cube gray scale sonography. The final diagnosis of hepatic lesions was 29 primary liver cancers, 4 metastases, 8 hemangiomas, 12 focal nodular hyperplasias, 2 inflammatory pseudotumors of the liver and 3 angiomyolipomas. The initiation time of enhancement in various lesions and enhancement duration after administration of contrast agent were compared. Vascular findings in lesions were classified as peripheral enhancement, homogenous enhancement, mosaic enhancement and no enhancement depending on microbubble signals in the lesion relative to the liver parenchyma. RESULTS: The initiation time of enhancement in hemangioma (48+/-12 s) was significantly later compared to other lesions (P<0.05). The enhancement duration of malignancies (69+/-33 s in primary liver cancer, 61+/-23 s in metastasis) was significantly shorter compared to benign lesions (P<0.05). Intranodular enhancement appearing at arterial phase and decreasing at portal venous phase was considered characteristic for malignancy. Intranodular enhancement did not appear earlier than the liver parenchyma, and peripheral enhancement pattern was regarded as positive findings for hemangioma. Intranodular enhancement appeared in the arterial phase, and homogenous enhancement pattern sustained in the whole portal venous phase were regarded as positive findings for focal nodular hyperplasia. No microbubble signals appeared in two inflammatory pseudotumors of the liver. CONCLUSION: C-cube gray scale sonography can demonstrate dynamic intranodular enhancement in various focal hepatic lesions. The information provided by this methodology may be useful in the differential diagnosis of hepatic lesions.

Adult↗

PubMed2003

Effects of Kupffer cell inhibition on liver function and hepatocellular activity in mice.

Kupffer cells are the tissue macrophages in the liver and play an important role in the defense mechanisms of the body. However, their role in liver function and hepatocellular activity remains unclear. This study was therefore undertaken to investigate the effect of gadolinium chloride-induced Kupffer cell dysfunction on liver function and hepatocellular signaling activity in mice and to establish an animal model for studying the role of Kupffer cells in vivo. Kunming mice were intraperitoneally injected with different doses of gadolinium chloride (GdCl3), a selective inhibitor of Kupffer cells, and the mice were sacrificed at different time periods following the drug administration. Hepatotoxicity and Kupffer cell function, as well as the levels of signaling molecules and inflammatory mediators in liver tissue, were measured. We demonstrated that the administration of 10-20 mg/kg GdCl3 caused apoptosis of Kupffer cells and blocked the Kupffer cell effector function, as shown by a decrease in CD68 expression and phagocytic activity. In addition, the NO, PGE2 and cAMP levels in the liver were also reduced significantly. Furthermore, 20 mg/kg GdCl3 decreased the levels of cNOS, PKC and NF-kappaB p65 expression by 26.6, 68 and 64%, respectively. In contrast, hepatotoxicity was not observed when the same doses of GdCl3 were used. Moreover, we found that Kupffer cell function and the NO, PGE2 and cAMP contents, as well as PKC and NF-kappaB p65 levels in the liver were only partially, but not fully recovered in up to six days following 20 mg/kg GdCl3 injection. However, the administration of higher doses of GdCl3 (40 mg/kg) caused both hepatotoxicity and Kupffer cell necrosis, as well as an increased release of TNF, NO, and PGE2 in the liver. These results indicate that administration of suitable doses of GdCl3 blocked the effector function of Kupffer cells selectively, but did not cause liver parenchymal cell toxicity, and provide a frame-work for the establishment of an animal model for studying the role of Kupffer cells in signaling in the liver. Lastly, the present study also provides evidence that shows there is a positive association between the expression of cAMP, PKC, or NF-kappaB and the levels of NO, PGE2 and TNF in the liver of Kupffer-cell-blocked mice, and suggests that Kupffer cells may play a part in mediating liver function and hepatocellular activity.

Adenosine Triphosphatases↗

PubMed2002

Endothelium-derived hyperpolarizing factor: is there a novel chemical mediator?

1. Endothelium-derived hyperpolarization (EDH) has been reported in many vessels and an extensive literature suggests that a novel, non-nitric oxide and non-prostanoid, endothelium-derived factor(s) may be synthesized in endothelial cells. 2. The endothelium-dependent hyperpolarizing factor, or EDHF, is synthesized by the putative EDHF synthase and mediates its cellular effects by either, directly or indirectly, opening K channels on vascular smooth muscle cells or, via hyperpolarization of the endothelial cell, by facilitating electrical coupling between the endothelial and the vascular smooth muscle cell. 3. The question of the chemical identity of EDHF has received considerable attention; however, no consensus has been reached. Tissue and species heterogeneity exists that may imply there are multiple EDHF. Leading candidate molecules for EDHF include an arachidonic acid product, possibly an epoxygenase product, or an endogenous cannabinoid, or simply an increase in extracellular K+. 4. An increasing body of evidence suggests that EDH, notably in the resistance vasculature, may be mediated via electrical coupling through myoendothelial gap junctions and the existence of electrical coupling may negate the need to hypothesize the existence of a true endothelium-derived chemical mediator. 5. In this paper we review the evidence that supports and refutes the existence of a novel EDHF versus a hyperpolarization event mediated solely by myoendothelial gap junctions.

Animals↗

PubMed2002

Large multifunctional proteasome 2 gene Arg60His variant in autoimmune thyroid disease in Shanghai Chinese.

OBJECTIVE: To investigate the relationship between Arg60His variant in the large multifunctional proteasome 2(LMP2) gene and autoimmunune thyroid disease (AITD) in Shanghai Chinese. METHODS: By means of PCR-restriction fragment length polymorphisms(RFLP) assay, the genotypes of Arg60His variant in the LMP2 gene were determined in 367 unrelated Shanghai Chinese, including 205 patients with AITD and 162 normal control individuals. The former group was further divided into two subgroups 78 subjects with positive thyrotrophin receptor antibody(TRAb) and 127 subjects with negative TRAb but positive either thyroglobulin antibody(TGAb),thyoid microsomal antibody(TMAb) or thyroid peroxidase antibody (TPOAb). RESULTS: Significant difference ( P = 0.000)of allele frequencies of R/H 60 in the LMP2 gene was observed between Shanghai Chinese (R 0.89,H 0.11) and white Caucasians (R 0.29, H 0.71)and was also observed between TRAb positive subgroup in AITD and normal controls. The frequencies of RH genotype and H allele in TRAb positive subgroup is significantly higher than those in normal controls( P = 0.037,0.047,respectively).In AITD group, the genotype and allele frequencies of Arg60His variant in the LMP2 gene showed no significant difference between other antibody(+) subgroups and antibody(-) subgroups. CONCLUSION: Arg60His variant in the LMP2 gene may be associated with the pathogenesis of AITD in Shanghai Chinese.

Asian People↗

PubMed2002

[Comparative analysis of serologic typing and HLA-II typing by micro-PCR-SSP].

OBJECTIVE: To evaluate the accuracy of polymerase chain reaction with sequence specific primers (PCR-SSP) in HLA-II genotyping and analyze the causes of the errors occurring during the genotyping. METHOD: Blood samples were obtained form patients with chronic renal insufficiency, leukemia or thalassemia and also from normal subjects. HLA-DR and -DQ genotyping of the sera from the 110 subjects was performed using micro-PCR-SSP and comparison was made with the results obtained from monoclonal antibody serologic typing. RESULT: Of the 110 samples detected by micro-PCR-SSP, 396 alleles of HLA-DR were identified in 99 cases and 22 of HLA-DQ in 11 cases, and 10% of the subjects were identified as homozygote individuals. Examination by both of the 2 methods in 67 cases indicated high rates of missed diagnoses and misdiagnoses by serologic typing with the diagnostic discrepancy as high as 38.81% and 50.75% for HLA-DR and -DQ respectively. The antigens DR 15/16, 11/12, 13/14, 8 or 12; DQ 5/6, 8/9 were among those that frequently gave rise to errors or confusion. CONCLUSION: Micro-PCR-SSP method can accurately detect the alleles of HLA-II antigens that are easy to be missed or mistaken by serological typing method.

Alleles↗

PubMed2002

[Analysis about clinical data of intrauterine infection of hepatitis B virus].

OBJECTIVE: To investigate a practical diagnostic method in clinic for fetuses infecting with hepatitis B (HBV) and study the mutual effects between fetal infection and clinical factors. METHODS: Venous blood was drawn from 144 cases of HBV carrier mothers and their neonates. HBV DNA was detected by polymerase chain reaction (PCR) and hybridization, HBV M was detected by enzyme linked immunoadsorbent assay (ELISA), and aspartate aminotransferase/alanine aminotransferase (AST/ALT) was detected by IFCC. Umbilical blood and femoral blood was taken from 40 of 144 neonates for HBV DNA detection. Clinical data, neonatal AST and ALT level were compared between fetal infection group and control group. RESULTS: (1) The fetal infectious rate was 22.9% (33/144). Comparing with peripheral venous blood sample, the sensitivity and positive predictive value of HBV DNA detected in cords was 100.0%, 80.0% respectively. Following up the infants, HBV DNA was found persistently positive in 7 of 28 intrauterine infectious infants 6 approximately 9 months after birth. HBsAg was found changing to be negative 1 month later in the infants with HBsAg positive at birth. (2) The fetal infectious rate in mothers with HBeAg (+) or HBV DNA (+) was 70.5%, 61.1% respectively which was significantly higher than that in mothers with HBeAg (-) or HBV DNA (-). P < 0.01. There was no significantly difference in mothers' age, gestational age, delivery way, birth weight (BW), body length (BL), Apgar score between fetal infectious group and control group. (3) The mean value of AST, ALT in fetal infectious group was (61.2 +/- 31.3) IU, (24.7 +/- 14.9) IU respectively, which was significantly higher than that in control group [(55.2 +/- 37.1) IU, (19.0 +/- 10.1) IU]. P < 0.01. CONCLUSIONS: (1) Detection of HBV DNA in cord blood is a sensitive index for diagnosing fetal infection, however detection of peripheral venous blood is with the significance of making correct diagnosis. (2) HBsAg or HBV DNA positive in mothers is one of the risk factors of intrauterine infection. There is no relationship among fetal infection and mothers' age, gestational age, delivery way, neonates' sex, BW, BL. (3) The liver function of neonates infected with HBV intrauterinely maybe impaired to some extent.

Adult↗

PubMed2001

Detection of tumor parenchymal blood flow in hepatic tumors: value of second harmonic imaging with a galactose-based contrast agent.

Purpose. To evaluate the detectability of tumor vascularity in hepatic tumors by second harmonic imaging with the administration of a microbubble contrast agent, Levovist. Materials and methods: Twenty-four patients with hepatic tumors (21 hepatocellular carcinoma, one focal nodular hyperplasia and two liver metastasis) were studied using Aloka SSD 5500 with the administration of Levovist. Intermittent harmonic gray-scale imaging (HGSI) and intermittent harmonic power Doppler imaging (HPDI) were performed on every tumor and the detectability of the two harmonic imaging modes were compared with that of dynamic CT. Results: Tumor vessels and tumor parenchymal blood flow were obtained in hypervascular tumors in the early arterial phase, and metastasis presented peripheral enhancement. When dynamic CT was taken as a gold standard, the sensitivity, specificity and accuracy of detecting tumor vascularity for intermittent HGSI were 55.6, 100 and 66.7%, and for intermittent HPDI were 83.3, 100 and 87.5%, respectively. The difference of detectability between the two modes was statistically significant (P<0.05). Depth of the lesion from the abdominal wall was a major factor affecting the detectability of tumor vascularity. Conclusion: With the administration of Levovist, intermittent HPDI was more sensitive than intermittent HGSI to demonstrate tumor vessels and tumor blood flow. Second harmonic imaging with Levovist would be a promising valuable means for investigating specific vascular features in hepatic tumors.

Journal Article↗

PubMedDate not supplied

Twenty-five years since the discovery of endothelium-derived relaxing factor (EDRF): does a dysfunctional endothelium contribute to the development of type 2 diabetes?

Twenty-five years ago, the discovery of endothelium-derived relaxing factor opened a door that revealed a new and exciting role for the endothelium in the regulation of blood flow and led to the discovery that nitric oxide (NO) multi-tasked as a novel cell-signalling molecule. During the next 25 years, our understanding of both the importance of the endothelium as well as NO has greatly expanded. No longer simply a barrier between the blood and vascular smooth muscle, the endothelium is now recognized as a complex tissue with heterogeneous properties. The endothelium is the source of not only NO but also numerous vasoactive molecules and signalling pathways, some of which are still not fully characterized such as the putative endothelium-derived relaxing factor. Dysfunction of the endothelium is a key risk factor for the development of macro- and microvascular disease and, by coincidence, the discovery that NO was generated in the endothelium corresponds approximately in time with the increased incidence of type 2 diabetes. Primarily linked to dietary and lifestyle changes, we are now facing a global pandemic of type 2 diabetes. Characterized by insulin resistance and hyperglycaemia, type 2 diabetes is increasingly being diagnosed in adolescents as well as children. Is there a link between dietary-related hyperglycaemic insults to the endothelium, blood flow changes, and the development of insulin resistance? This review explores the evidence for and against this hypothesis.

Animals↗

PubMedDate not supplied

Correlation of serum VEGF levels with clinical stage, therapy efficacy, tumor metastasis and patient survival in ovarian cancer.

Vascular endothelial growth factor (VEGF) has been shown to play an important role in tumor growth and progression. However, the clinical implications of VEGF expression in ovarian tumors are not fully understood. We therefore investigated the serum level of VEGF in patients with ovarian tumors and explored the potential use of VEGF as a tumor marker for diagnosis, treatment and prognosis of human ovarian cancer. The serum VEGF (sVEGF) levels in 120 patients with ovarian carcinoma, 25 patients with benign ovarian tumor and 90 healthy female blood donors were measured by an enzyme-linked immunosorbent assay in this study. We also determined the levels of sVEGF in patients with epithelial ovarian cancer before and after surgery. Our results showed that: (i) ovarian cancer patients had significantly higher levels of sVEGF compared to those of patients with benign ovarian tumor or those of healthy individuals. As a cut-off at 100 pg/ml, the sensitivity and specificity of sVEGF levels for diagnosing ovarian carcinoma were 77.1% and 87%, respectively. (ii) sVEGF levels were markedly elevated in patients with advanced stage or poorly-differentiated ovarian cancer, as well as in those with more ascites (>500 ml), as compared to patients with early stage and well-differentiated ovarian cancer, or those with less ascites (<500 ml). However, there was no significant difference in sVEGF levels among different pathological subtypes of ovarian carcinoma. (iii) The post-operative sVEGF levels were significantly lower than the pre-operative sVEGF levels. (iv) We measured significantly higher levels of sVEGF in patients with metastasis as compared to patients lacking metastasis. Lastly (v) the average survival-time in patients with higher levels of sVEGF (>100 pg/ml) was 28 months, while the average survival-time in patients with lower levels of sVEGF (<100 pg/ml) was 35 months, indicating that the elevations in sVEGF level are correlated with patient survival and tumor metastasis in ovarian carcinoma. These data suggest that VEGF may be a useful serological biomarker for clinical diagnosis and prognosis of ovarian cancer, for follow-up of ovarian tumor metastasis and for monitoring the efficacy of therapy in patients with ovarian carcinomas.

Adult↗