Biomedical subjects

Q Li

Publications and source records attributed to Q Li.

1,149 records · Page 64Linked to original sources

PubMedDate not supplied

Effect of NF-kappaB constitutive activation on proliferation and apoptosis of gastric cancer cell lines.

OBJECTIVE: To observe whether there is constitutive activation of nuclear transcription factor kappaB (NF-kappaB) and its effect on proliferation and apoptosis of human gastric cancer cell lines. METHODS: Nuclear/cytoplasmic protein expression of NF-kappaB was analyzed by Western blot in four different gastric cancer cell lines. Trans AM(TM) NF-kappaB p65 Kit was used for detecting the difference of p65 activity. The effect of PDTC (pyrrolidine dithiocarbamate), a specific inhibitor of NF-kappaB on the proliferation of gastric cancer cells, was measured by MTT (3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide) method. The apoptotic rates of AGS and SGC-7901 gastric cancer cell lines were measured with flow cytometer (FCM) after treatment by PDTC. RESULTS: The constitutive activations of NF-kappaB were identified in four gastric cancer cell lines. The expression of activated subunit of p50 was lower in AGS cell line, and higher in MKN28, MKN45 and SGC-7901 cell lines. The expression of activated subunit of p65 was lower in MKN28 and MKN45 cell lines, and higher in AGS and SGC-7901 cell lines. Both the activity of NF-kappaB and the cell proliferation were significantly inhibited in experimental group treated by PDTC, compared with control groups (p<0.01). An increased apoptotic rate and a decreased proliferating activity were observed after the gastric cancer cells were exposed to PDTC for 24 h. CONCLUSIONS: These results suggested that the constitutive activation and the protein expression of NF-kappaB are different in gastric cancer cell lines. PDTC can inhibit NF-kappaB activity and cell proliferation, which related to an increased cell apoptosis. The results disclosed that NF-kappaB could be a potential therapeutic target for solid tumor therapy.

Adenocarcinoma↗

PubMedDate not supplied

Drinking water source and spontaneous abortion: A cross-sectional study in a rural Chinese population.

The authors examined the association between the risk of spontaneous abortion and the type of drinking water source in a rural Chinese population. Information about pregnancy outcomes and various exposures was collected by means of a detailed interview questionnaire. 2,876 pregnancies occurring in 1989-1993 among 2,201 nonsmoking and non-alcohol-drinking women were analyzed by logistic regression. Generalized estimating equations were used to adjust for correlations between multiple pregnancies in the same woman. The use of pond water as a drinking water source was associated with a higher risk of spontaneous abortion than the use of well or river water (odds ratio, 1.63; 95% confidence interval, 1.11 to 2.39), adjusting for potential confounders. More studies are needed to identify the agents responsible for the observed association. The results of this study emphasize the importance of monitoring potential drinking-water contamination in communities.

Abortion, Spontaneous↗

PubMedDate not supplied

The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers.

The effects of berberine (BBR) on the pharmacokinetics of ciclosporin A (CsA) were examined in healthy volunteers. Six healthy male volunteers were orally treated with 0.3 g BBR, twice daily for 10 days. Pharmacokinetic investigations on CsA at 6 mg/kg were done both before and at the end of the BBR treatment period. Another six healthy male volunteers were involved in the pharmacokinetic study with 3 mg CsA/kg, in which the subjects orally received the second single dose of 3 mg CsA/kg, followed by a single oral dose of 0.3 g BBR. The blood CsA concentrations were determined by fluorescence polarization immunoassay. In the pharmacokinetic study with 6 mg CsA/kg, BBR caused no significant changes in the pharmacokinetic parameters of CsA. However, in the trial with 3 mg CsA/kg, the average percentage increase in area under the blood concentration-time curve of CsA was 19.2% (P < 0.05) and the mean C12 increased to 123 microg/l from 104 microg/l (P < 0.05), without altering elimination half-life (t(1/2)), maximum blood drug concentration (Cmax), time to Cmax (tmax), apparent oral clearance (CL/F). The present results suggest that BBR can increase the oral bioavailability of CsA at the dosage of 3 mg/kg. The BBR-mediated increase in CsA bioavailability may be partly attributed to a decrease in liver and/or intestinal metabolism through the inhibition of CYP3A4 in the liver and/or gut wall. The BBR-induced increase in emptying time of stomach and small intestine might be another reason for the increase in CsA bioavailability. However, the speculation should be proved by further investigation.

Adult↗

PubMedDate not supplied

Immunological abnormalities in HTLV-I-associated myelopathy: spontaneous release of interleukin-2 and interleukin-2 receptor by peripheral blood lymphocytes.

Ten patients with human T lymphotropic virus type I-associated myelopathy (HAM), 5 asymptomatic HTLV-I carriers and 11 healthy normal volunteers were studied to determine if peripheral blood lymphocytes spontaneously release IL-2 and soluble IL-2 receptors. Peripheral blood lymphocytes obtained from HAM patients proliferated spontaneously when cultured for 5 days in vitro. Proliferating cells were CD3+ lymphocytes and both CD4+ cells and CD8+ cells as shown by morphologic and immunohistochemical observations. These T cell responses were also found in asymptomatic carriers, but the responses were not as marked as those of HAM patients. IL-2 activity in the culture supernatants was much higher in HAM patients than in asymptomatic carriers; IL-2 activity correlated well with the intensity of spontaneous proliferation of lymphocytes. Furthermore, soluble IL-2 receptors in the cell-free supernatants from HAM patients were markedly increased compared to those from asymptomatic carriers. These results indicate that spontaneous proliferation of T cells is intimately related to HTLV-I infection and is probably due to autocrine or paracrine pathways which involve IL-2 and IL-2 receptor system.

Adult↗

PubMedDate not supplied

Ultrastructural localization of endothelin-1 in nonneoplastic, hyperplastic, and neoplastic adrenal gland.

Endothelin (ET)-1 is a 21-amino acid peptide with potent vasopressor and vasoconstrictive properties. Biochemical and recent histochemical studies have shown that this peptide is present in human adrenal cortex. This study was intended to determine ET-1 immunoreactivity in human adrenal cortex and cortical adenoma, and hyperplasia ultrastructurally. Light microscopical examination confirmed recent findings of ET-1 immunoreactivity in the three cortical zones (but not in the medulla) as well as in cortical adenoma and cortical hyperplasia. The immunoreactivity in the cortex and adenoma appeared in the cytoplasm in the form of vacuolar structures and grains. Focally, the cell membranes also showed immunoreactive staining. Electronmicroscopical investigation revealed ET-1 immunoreactive products adjacent to the outer surface of the membrane of lipid bodies, in mitochondria and rough endoplasmic reticulum and focally on the cell membrane, but no immunolabeling was seen in the medulla. The localization of ET-1 in the endoplasmic reticulum indicates that this peptide is synthesized in the cortical cells. Its localization in the membrane of the lipid bodies and in the mitochondria suggests that it takes part in synthesis and/or secretion of steroid hormones. The focally immunolabeled cell membranes may be dependent on ET-1 binding to ET receptors.

Adrenal Gland Neoplasms↗

PubMedDate not supplied

Inhibition of antigen-specific IgE production by antigen coupled to membrane IgE peptide.

The membrane IgE peptide (MEP) encompassing 20 amino acids proximal to the C terminus of membrane IgE molecules, and secretory IgE peptides (SEP), spanning CH epsilon 1 to 4 domain were synthesized according to IgE genomic and cDNA sequences. Inhibition of anti-KLH and anti-BGG IgE, but not IgG responses was observed in mice treated with MEP-protein but not SEP-protein conjugates in complete/incomplete Freund's adjuvant. Only IgE responses directed toward proteins to which MEP was conjugated, were inhibited, while IgE responses to a concomitantly injected, unrelated antigen were not. Inhibition of antigen-specific IgE was also not correlated with levels of anti-MEP or anti-IgE antibodies, moreover, levels of total IgE remained comparable among mice treated with MEP-protein conjugates, native or glutaraldehyde-modified protein carriers. This observation may have significant import on future design of IgE immunotherapy. Treatment of MEP conjugated allergens prevents formation of IgE-anti-IgE complexes because the MEP sequence is absent from the secretory IgE.

Amino Acid Sequence↗

PubMedDate not supplied

Glycosylated extracellular domains of membrane immunoglobulin M contribute to its association with mb-1/B29 gene products and the B cell receptor complex.

It has recently become clear that the B cell antigen receptor, membrane immunoglobulin (mIg) is part of a complex composed of a number of different polypeptides. In a manner analogous to the T cell receptor, mIg has been found to be associated with several tyrosine kinases, and other proteins, which although not kinases themselves become targets of kinase activity upon binding of mIg to antigen. Thus the B cell receptor complex appears to be a structure whose function during signal transduction is to facilitate the interaction of tyrosine kinases with their proper substrates, and to coordinate the phosphorylation of these proteins with the binding of antigen to mIg. In an effort to understand the nature of the interactions which mediate the organization of the B cell receptor complex, we have explored binding of components of the complex including Ig-alpha and Ig-beta to IgM. Previous results have indicated that binding was mediated by transmembrane domains. Our results indicate that extracellular domains of IgM may also contribute to its association with Ig alpha and beta and other members of the B cell receptor complex.

Amino Acid Sequence↗

PubMedDate not supplied

Fluorescence spectroscopic study of the interaction of saporin with phospholipid vesicles.

Saporin-S6 (SO-6) is a type-1 ribosome-inactivating protein purified from the seeds of Saponaria officinalis. The fluorescence characteristics of SO-6 were studied in the presence and absence of phospholipids. The interaction of SO-6 with DMPG or DMPC vesicles results in a decrease in the fluorescence emission intensity of tryptophan without any shift in the emission maximal wavelength. The results of fluorescence titration indicate that DMPG/SO-6 saturation molar ratio is 100: 1, but the binding of DMPC with SO-6 does not reach a saturating plot. A shielding of the tryptophan fluorescence from quenching by acrylamide on interaction with the phospholipids was observed, and this shielding was more pronounced in the presence of DMPG. The interaction of SO-6 with DMPG vesicles is stronger in the liquid-crystalline phase than in the gel phase. Extrinsic fluorescence studies indicated that the interaction of the protein with DMPG vesicles does not modify the phase transition temperature of the lipid, but decreases the amplitude of the change of fluorescence anisotropy associated with the co-operative melting of 1,6-diphenyl-1,3,5-hexatriene (DPH)-labelled vesicles. These results indicate that both electrostatic and hydrophobic components are involved in the SO-6-lipid vesicle interaction.

Acrylamide↗

PubMedDate not supplied

Increased level of serum hepatocyte growth factor/scatter factor in liver cancer is associated with tumor metastasis.

Hepatocyte growth factor/scatter factor (HGF/SF) has been shown to play an important role in tumor migration and metastasis. We therefore investigated the relationship between HGF/SF expression and metastasis of human liver tumors. The serum HGF/SF levels in 41 patients with primary hepatocellular carcinoma (HCC; 22 patients with metastasis, 19 patients without metastasis); 4 patients with benign hepatic tumor, 4 patients with secondary hepatic carcinoma, and 12 healthy blood donors, were measured by sandwich enzyme-linked immunosorbent assay (ELISA) in this study. Our results show that liver tumor patients have significantly higher serum levels of HGF/SF compared to healthy blood donors. However, there is no difference between the serum HGF/SF levels in patients with primary HCC and patients with secondary HCC or benign hepatic tumors. In addition, we measured significantly higher levels of HGF/SF in serum from HCC patients with metastasis compared to HCC patients without metastasis, indicating that the elevations in serum HGF/SF level correlated positively with the tumor metastasis in human HCC. These findings appear to suggest that HGF/SF may be a useful serological biomarker for clinical diagnosis and follow-up of HCC metastasis, and suggest that larger scale studies in patients with hepatomas are warranted.

Biomarkers, Tumor↗

PubMedDate not supplied

Increased expression of nitric oxide synthase and dendritic injury in simian immunodeficiency virus encephalitis.

OBJECTIVES: Widespread dendritic injury may be one mechanism involved in the neurologic impairment that occurs in HIV-1 infection. The objectives of this study were to quantitate the extent of dendritic injury in a primate model of central nervous system (CNS) infection, investigate the role of nitric oxide (NO) as a mediator of neuropathologic changes, and evaluate the relation of these changes to cognitive and motor function. STUDY DESIGN/METHODS: Cognitive and motor function was assessed in rhesus macaque monkeys infected with simian immunodeficiency virus (SIV). In situ hybridization, immunohistochemistry, and quantitative image analysis were employed to assess the relations among productive infection, NO synthase (iNOS), and dendritic injury. RESULTS: Productive infection of cells of the macrophage lineage in CNS is associated with inflammation, increased expression of iNOS, and dendritic injury. The tests of cognitive and motor function employed were abnormal in both animals that had evidence of productive infection and those that did not. CONCLUSIONS: Increased NO accompanying productive infection and encephalitis may be one cause of neuronal injury in lentivirus infections of the CNS. Extension of tests of cognitive and motor function to late-stage AIDS in rhesus monkeys is needed to assess the potential role of NO-induced dendritic damage in lentiviral encephalopathy/AIDS dementia complex.

Animals↗

PubMedDate not supplied

Immunohistochemical and DNA sequencing analysis on human mismatch repair gene MLH1 in cervical squamous cell carcinoma with LOH of this gene.

BACKGROUND: The human MLH1 gene (hMLH1) is one of the DNA mismatch repair genes. Defects in these genes are believed to be the underlying cause of microsatellite instability (MSI). MSI has been demonstrated in many human cancers such as colon cancer and some female-specific tumors. The hMLH1 gene can be inactivated by genetic mutation or by hypermethylation of its promoter region, which often causes cessation of hMLH1 protein production. We were prompted by our previous finding of 43% of cervical cancers and their precursors with a loss of heterozygosity (LOH) of the hMLH1 gene to investigate whether it is inactivated during the carcinogenesis of cervical cancer. MATERIALS AND METHODS: hMLH1 protein production was assessed by immunohistochemistry, and nucleotide sequence analysis were performed on all exons of the hMLH1 gene. RESULTS: In 11 cases of invasive cervical cancer, among which 7 had LOH of the hMLH1 gene, immunohistochemistry provided no evidence for cessation of hMLH1 protein production. In addition, no mutations were found in any of the 19 hMLH1 gene exons. CONCLUSIONS: The activity of hMLH1 gene might not be disturbed in the development of cervical cancer although a proportion of the cases had lost one of its hMLH1 gene copies.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Association between the level of ERCC-1 expression and the repair of cisplatin-induced DNA damage in human ovarian cancer cells.

Nucleotide excision repair (NER) is responsible for the repair of platinum-DNA lesions. ERCC-1 is a critical gene within the NER pathway, and cells without a functional ERCC-1 do not repair cisplatin-caused DNA damage. The present study was therefore designed to evaluate the relationship between the expression of ERCC-1 and the repair of cisplatin-induced DNA adducts in human ovarian cancer cells in vitro. One hour exposure of MCAS cells to cisplatin yielded an approximately two-fold increment in the levels of ERCC-1 mRNA and ERCC-1 protein, as determined, respectively, by Northern and Western blottings. In addition, nuclear run-on assay showed that ERCC-1 gene transcription rate was increased to about the same extent as steady-state ERCC-1 mRNA and protein, in response to cisplatin treatment. However, the levels of ERCC-1 mRNA, ERCC-1 protein, and ERCC-1 transcript in MCAS cells are two-fold lower than those in A2780/CP70 cells, as previously reported. Furthermore, the repair of cisplatin-DNA adducts in MCAS cells, as measured by atomic absorption spectrometry, is also nearly two-fold less than that in A2780/CP70 cells, indicating a strong association between the level of ERCC-1 expression and the activity of excision repair in these two human ovarian tumor cell lines. These results suggest that ERCC-1 may be a useful marker to monitor the repair of platinum-DNA damage in tumor cells, and further highlight that potential pharmacological approaches which specifically inhibit ERCC-1 expression may increase cellular sensitivity to cisplatin.

Cell Nucleus↗

PubMedDate not supplied

Dopamine activates ATP-sensitive K+ currents in rat retinal pericytes.

The relatively sparse vasculature of the retina minimizes obstruction to incoming light, but also poses a challenge to fulfilling the metabolic demands of retinal neurons. An efficient process for distributing energy supplies to areas of need is likely to involve neuron-derived vasoactive signals. However, knowledge of the mechanisms by which capillary perfusion is regulated by neuron-to-vascular signaling is limited. Potential targets of vasoactive molecules released from nerve cells are the pericytes, which are positioned on the endothelial walls of microvessels and are thought to play a role in controlling the microcirculation. In this study, we assessed the effect of dopamine on pericyte physiology. Because dopaminergic neurites are closely associated with microvessels that express dopamine receptors, this molecule is a putative neuron-to-capillary signal, as well as neurotransmitter. We used the perforated-patch configuration of the patch-clamp technique to monitor the whole-cell currents of pericytes located on microvessels freshly isolated from the adult rat retina. In 43% (58/134) of the sampled pericytes, we found that dopamine reversibly activated a hyperpolarizing current, which increased the membrane potential by 19 +/- 1 mV. This dopamine-induced current was inhibited by the ATP-sensitive potassium (KATP) channel blocker, glibenclamide. Consistent with a signaling pathway involving D1 dopamine receptors, adenylate cyclase and protein kinase A (PKA), the selective D1 antagonist, SCH23390, inhibited the hyperpolarizing effect of dopamine; the activator of adenylate cyclase, forskolin, mimicked the dopaminergic effect, and H89, which inhibits PKA, significantly reduced the hyperpolarization induced by dopamine. Taken together, our experiments indicate that a mechanism involving D1 dopamine receptors, adenylate cyclase, and PKA activates KATP currents in retinal pericytes. Our observations support the hypothesis that, in addition to being a neuromodulator, dopamine also serves as a signal linking neuronal activity with the function of the pericyte-containing microvasculature.

Adenosine Triphosphate↗

PubMedDate not supplied

Effect of protein kinase modulators on the regulation of cathepsin B activity in THP-1 human monocytic leukemia cells.

Cathepsin B (CB), a lysosomal cysteine proteinase, is implicated in cancer metastasis and inflammatory tissue injury. We examined the effects of the protein kinase agonists and inhibitors on the regulation of CB activity in THP-1 human monocytic cells by two macrophage activators, lipopolysaccharide (LPS) and interferon- (IFN- ). CB elevation induced by LPS alone or LPS followed by IFN- was blocked by protein kinase C (PKC) inhibitors staurosporine, H-7, phloretin and bisindolylmaleimide, and by cyclic nucleotide-dependent protein kinase inhibitors HA 1004, H-8, H-89 and cAMP-dependent protein kinase (PKA) inhibitor. The CB activity by LPS and IFN- were augmented by diacylglycerol kinase inhibitor. PKC activator, phorbol 12-myristate 13-acetate (PMA) and PKA activator, dibutyryl cAMP could replace LPS in priming the cells for IFN- stimulation but 8-bromo-cGMP did not. These findings suggest that the activation of PKC and PKA appears to be involved at least in part in the induction of CB activity in THP-1 cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMedDate not supplied

Effect of interleukin-1 alpha and tumour necrosis factor-alpha on cisplatin-induced ERCC-1 mRNA expression in a human ovarian carcinoma cell line.

Enhanced expression of the human excision repair enzyme ERCC-1 is associated with cellular and clinical resistance to cisplatin in human ovarian cancer. High levels of expression of ERCC-1 appear to be associated with increased activity of the nucleotide excision repair pathway. We therefore began to examine the effect of some cisplatin resistance modulators on cisplatin-induced ERCC-1 mRNA expression in the human ovarian carcinoma cell line, A2780/CP70. Cisplatin exposure to A2780/CP70 cells in culture resulted in a four- to five-fold induction for steady-state ERCC-1 mRNA, that was dose- and time-dependent. The biological agents interleukin (IL)-1 alpha and tumour necrosis factor (TNF)-alpha have been shown to enhance cisplatin cytotoxicity in vitro. IL-1 alpha inhibited cisplatin induction of ERCC-1 mRNA levels in our system. The effect of IL-1 alpha was sequence dependent, in that the maximum inhibitory effect was observed with 24-hour pretreatment with IL-1 alpha. By contrast, TNF-alpha had little effect on ERCC-1 mRNA induction by cisplatin. Low-temperature hyperthermia (42 degrees C) almost completely suppressed ERCC-1 mRNA induction in these cells. These findings suggest that the enhancement effect of some agents on cisplatin sensitivity in ovarian tumour cells may be through downregulating ERCC-1 expression.

Cisplatin↗