Search PubMed⌕ Search

Biomedical subjects

N Ge

Publications and source records attributed to N Ge.

At least 19 recordsLinked to original sources
PubMed2001

Involvement of chemokine receptors in breast cancer metastasis.

Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.

Actins↗
PubMed2001

Interferon-gamma activates outwardly rectifying chloride channels in the human bronchial epithelial cell line BEAS-2B.

The mechanism of increased chloride currents by inflammatory cytokine, interferon-gamma (IFN-gamma), was investigated in cultured a human bronchial epithelial cell line (BEAS-2B) using cell-attached and inside-out patch configurations. The channel sensitive to chloride ion was activated by forskolin, an activator of adenylate cyclase, or 100 microM dibutyryl 5'-cyclic monophosphate in cell-attached configurations. The conductance of this channel was 40 +/- 4 pS in symmetrical 150 mM chloride solution between membrane potentials of 0 to mV, and this channel was blocked by 500 microM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), suggesting that this channel was an outwardly rectifying chloride channel (ORCC). Treatment of 10-1000 U/ml IFN-gamma for 3 hours, but not IFN-alpha, significantly increased channel activities of ORCC, and this activation was observed at least 24 hours after treatment. Erythromycin, a macrolide antibiotic, at a concentration of 100 microM inhibited the activation of ORCC induced by IFN-gamma. The findings of the present study indicate that increased mucus secretion during inflammation might be partly due to activation of chloride permeability by cytokine and erythromycin might improve oversecretion of mucus from bronchial epithelium by blocking ORCC.

Bronchi↗
PubMed2001

[Social economical status, behaviors and environment as the risk factors of tuberculosis in Chengdu China].

OBJECTIVE: To study the risk factors of pulmonary tuberculosis in Chengdu, Southwest China. METHODS: A population-based case-control study was used which included 174 cases selected from 12 communities in Chengdu and 174 controls selected from registered population with normal chest radiograph. Cases were active TB patients which were matched for age, sex with controls, then interviewed by trained interviewers using a standardized questionnaire. RESULTS: Social economic status measured by education, occupation and income did not show obvions influence to TB; It found that the active smoking, passive smoking, type of cigarettes and alcohol consumption had no significanct effects on TB during logistic regression analysis. The study showed that a person who was smoking and also alcohol intake had a higher risk to get TB (OR = 6.12, 95% CI = 1.15 - 32.49). Significant association was showed in the Dose-Response Analysis (OR = 1.37, 95% CI = 1.30 - 2.30). Crowded living space (OR = 1.14, 95% CI = 1.05 - 1.25), degree of darkness (OR = 2.18, 95% CI = 1.11 - 4.27) and moisture (OR = 4.06, 95% CI = 2.25 - 7.33), poor sanitary (OR = 3.03, 95% CI = 1.22 - 4.44), airpollution of working environment, which were filled with dusts (OR = 2.35, 95% CI = 1.18 - 4.70) and chemical fumes (OR = 5.15, 95% CI = 1.44 - 18.40) were strongly associated with pulmonary tuberculosis. BMI also had strong relationship with TB (OR = 4.72, 95% CI = 2.68 - 8.33). CONCLUSION: Poor environment and exposure to dust and chemical fume under working condition, low BMI, smoking combining alcohol consumption were the risk factors of adult pulmonary tuberculosis in Chengdu, China.

Adolescent↗
PubMed2001

[Smoking and alcohol consumption as risk factors of pulmonary tuberculosis in Chengdu: a matched case-control study].

OBJECTIVE: The aim of this study was to assess the relationship between personal behaviors (smoking and alcohol consumption) and contracting pulmonary tuberculosis. METHODS: 346 persons (173 cases and 173 controls) were selected from 12 communities of Chengdu area, all the cases were active TB patients (by WHO criteria) from March 1996 to March 1997. Controls were matched for age, sex and living district. Subjects were interviewed face to face by trained interviewers using questionnaires. RESULTS: The results of univariate analysis showed that active smoking (OR = 2.12, P = 0.006), passive smoking (OR = 1.55, P = 0.04), type of cigarettes (OR = 1.31, P = 0.005) and alcohol consumption (OR = 1.81, P = 0.008) were significantly associated with TB. Yet, multivariate logistic regression analysis did not find smoking or alcohol consumption being in independent association with TB, but it showed that persons who were smokers with the addition of alcohol consumption had a higher risk to contract TB (OR = 7.729, 95% C.I. = 1.5215-39.2634). Significant association was noted in the dose-response analysis (OR = 1.73, 95% C.I. = 1.300-2.3028). CONCLUSION: These data indicate that smoking alone or sole alcohol consumption bears no relationship with TB, but smoking plus alcohol abuse is probably a risk factor for pulmonary tuberculosis in Chengdu, and in this connection, a proposal of prospective study to further demonstrate this risk factor is warranted.

Adolescent↗
PubMed1999

Theoretical elucidation of activity differences of five phenolic antioxidants.

AIM: To verify the effectiveness of structure-activity relationship (SAR) and theoretical calculation methods for antioxidants. METHODS: Preliminary elucidation on the differences of activities of 5 antioxidants was performed by SAR. Then semiempirical quantum chemistry method AM1 was employed to calculate the delta HOF value, the difference between the heat of formation of antioxidant and its free radical, which was used as a theoretical parameter to elucidate the differences of activities of the antioxidants thoroughly. RESULTS: delta HOF values of antioxidants were obtained as follows: ferulic acid, 150.58 kJ.mol-1; anion of ferulic acid, 122.64 kJ.mol-1; modified ferulic acid, 137.70 kJ.mol-1; anion of modified ferulic acid, 118.99 kJ.mol-1; salvianic acid, 134.17 kJ.mol-1; rutin, 137.83 kJ.mol-1, L-EGCG, 124.39 kJ.mol-1; paeonol, 176.79 kJ.mol-1. The differences of the antioxidant activities were elucidated, and how to further enhance the antioxidant activity was investigated as well. CONCLUSION: The SAR and calculation methods are rather effective to elucidate the differences of antioxidant activities, and present some new clues for structural modification of antioxidants to increase their activities.

Acetophenones↗
PubMed1998

Femtosecond dynamics of electron localization at interfaces

The dynamics of two-dimensional small-polaron formation at ultrathin alkane layers on a silver(111) surface have been studied with femtosecond time- and angle-resolved two-photon photoemission spectroscopy. Optical excitation creates interfacial electrons in quasi-free states for motion parallel to the interface. These initially delocalized electrons self-trap as small polarons in a localized state within a few hundred femtoseconds. The localized electrons then decay back to the metal within picoseconds by tunneling through the adlayer potential barrier. The energy dependence of the self-trapping rate has been measured and modeled with a theory analogous to electron transfer theory. This analysis determines the inter- and intramolecular vibrational modes of the overlayer responsible for self-trapping as well as the relaxation energy of the overlayer molecular lattice. These results for a model interface contribute to the fundamental picture of electron behavior in weakly bonded solids and can lead to better understanding of carrier dynamics in many different systems, including organic light-emitting diodes.

Journal Article↗
PubMed1998

Step-down trend tests for identifying the minimum effective dose.

Many authors, most recently Tamhane, Hochberg, and Dunnett (18), have studied the problem of determining the minimum effective dose in dose-response studies. Based on past research and on findings from their own extensive simulation study, which covered a wide range of balanced normal homoscedastic situations, Tamhane et al. recommended a procedure they called SD2L, since it exhibited good performance in almost all the situations they studied. This method is a step-down procedure with a simple linear contrast-based trend test at each step. In this paper, we demonstrate that replacing the linear contrast trend test by Bartholomew's test leads to a procedure, SD2B, that consistently outperforms SD2L. In addition to the balanced normal homoscedastic framework, the finite sample performance of these procedures is also explored under unbalanced and/or heteroscedastic conditions. A third procedure, SD2W, which replaces the linear contrast test by Welch's test, offers some improvement over SD2B in a few heteroscedastic situations. In many cases, the increase in efficiency of SD2B and SD2W over SD2L exceeds 10%.

Animals↗
PubMed1996

Pathogenesis of HIV-1 associated neurodegeneration.

A significant number of people infected with the human immunodeficiency virus (HIV) develop neurologic complications. The AIDS dementia complex is frequently accompanied by HIV encephalitis, which is characterized at the neuropathologic level by loss of neuronal subpopulations in the neocortex, limbic system, and basal ganglia in association with synaptic and dendritic damage, astrogliosis, and formation of microglial nodules and multinucleated giant cells. Recent studies have shown that the extent of neurodegeneration in this condition correlates directly with the amount of HIV-1 antigen in the brain. HIV-1 infection of the brain could result in neurodegeneration via neurotoxic effects of viral products (e.g., gp 120, Nef, Tat) and/or via alterations in the expression of host factors. The latter may include increased production of potentially detrimental factors such as cytokines, excitotoxic amino acids, free oxygen radicals, and bioactive lipid mediators as well as interference with the production or action of neurotrophic/protective factors. Derangements of the neuronal calcium homeostasis, lipid peroxidation, and induction of programmed cell death (apoptosis) may all play a role as final common pathogenetic pathways in HIV-1-induced neurodegeneration. Recent studies in transgenic mice (over)expressing HIV- or host-derived proteins in their central nervous system indicate that distinct neuronal populations may differ in their susceptibility to specific pathogenic factors. For example, glutamate-receptor-bearing pyramidal neurons were particularly susceptible to neurodegeneration promoted by HIV-1 products, whereas interneurons were more sensitive to the neurotoxic effects mediated by cytokines. For the design of effective treatments for the HIV-1-associated cognitive/motor complex, it will be important to determine whether the neurologic deficits in this entity result from global neuronal dysfunction or relate more specifically to the impairment of distinct neuronal subpopulations. It will also be critical to examine diverse in vitro and in vivo models to help decide which of the many pathogenetic processes that may be at work in this complex disease constitute the most promising therapeutic targets.

AIDS Dementia Complex↗
PubMed1995

The inhibitory effect of apolipoprotein E4 on neurite outgrowth is associated with microtubule depolymerization.

Evidence is presented for the differential effects of two isoforms of apolipoprotein (apo) E, apoE3 and apoE4, on neurite outgrowth and on the cytoskeleton of neuronal cells (Neuro-2a) in culture. In the presence of a lipid source, apoE3 enhances and apoE4 inhibits neurite outgrowth. Immunocytochemical studies demonstrate that there is a higher concentration of apoE3 than apoE4 in both the cell bodies and neurites. Cells treated with apoE4 showed fewer microtubules and a greatly reduced ratio of polymerized to monomeric tubulin than did cells treated with apoE3. The effect of apoE4 on depolymerization of microtubules was shown by biochemical, immunocytochemical, and ultrastructural studies. The depolymerization of microtubules and the inhibition of neurite outgrowth associated with apoE4 suggest a mechanism whereby apoE4, which has been linked to the pathogenesis of Alzheimer's disease, may prevent normal neuronal remodeling from occurring later in life, when this neurodegenerative disorder develops.

Actins↗
PubMed1995

Fragmentation of the neuronal cytoskeleton in the Lewy body variant of Alzheimer's disease.

We studied neuronal alterations in the Lewy body variant of Alzheimer's disease (LBV) with a monoclonal antibody (SMI32) against non-phosphorylated neurofilament proteins, and compared them with the alterations found in pure Alzheimer's disease (AD). A characteristic granular and fragmented appearance of SMI32-immunolabeled pyramidal neurons in layers 3 and 5 of the neocortex occurred in 78% of the LBV cases and was not found in the pure AD cases. Lewy bodies (LBs) in pyramidal neurons in layers 5 and 6 immunoreacted with SMI32 in 44% of the LBV cases. These alterations may be associated with the cognitive deficits found in LBV and are suggestive of an underlying, widespread pathology that includes both disruption of the neurofilamentous cytoskeleton and formation of LBs.

Aged↗
PubMed1995

Neurodegeneration in the central nervous system of apoE-deficient mice.

Apolipoprotein E (apoE) is involved in the development and regeneration of the central nervous system (CNS). ApoE may also be necessary to maintain the integrity of the synapto-dendritic complexity. We analyzed the synaptic alterations in the CNS of apoE-deficient (knockout) mice during the aging process. In apoE-deficient homozygous mice, there was an age-dependent 15 to 40% loss of synaptophysin-immunoreactive nerve terminals and microtubule-associated protein 2-immunoreactive dendrites in the neocortex and hippocampus, when compared to controls. Dendritic alterations were observed as early as 4 months of age. Ultrastructural analysis revealed extensive dendritic vacuolization and disruption of the endomembrane system and cytoskeleton in apoE-deficient homozygous mice. Further immunocytochemical studies of the neuronal cytoskeleton showed that in apoE-deficient mice there was a decrease in the immunoreactivity of alpha and beta tubulin (but not kinesin) in the cell bodies and processes. These results support the contention that apoE might play an important role in maintaining the stability of the synapto-dendritic apparatus and that altered or deficient functioning of this molecule could underlie the synaptic and cytoskeletal alterations in Alzheimer's disease.

Aging↗
PubMed1995

The precursor protein of non-A beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system.

Non-A beta component of Alzheimer's disease amyloid (NAC) is the second component in the amyloid from brain tissue of patients affected with Alzheimer's disease. Its precursor protein (NACP) was shown to be a brain-specific protein. In rat brain, NACP was more abundant in the neocortex, hippocampus, olfactory bulb, striatum, thalamus, and cerebellum and less abundant in the brain stem. Confocal laser microscopy analysis revealed that anti-NACP immunostaining was colocalized with synaptophysin-immunoreactive presynaptic terminals. Ultrastructural analysis showed that NACP immunoreactivity was associated with synaptic vesicles. NACP sequence showed 95% identity with that of rat synuclein 1, a synaptic/nuclear protein previously identified in rat brain, and good homology with Torpedo synuclein from the electric organ synapse and bovine phosphoneuroprotein 14 (PNP-14), a brain-specific protein present in synapses. Therefore, NACP is a synaptic protein, suggesting that synaptic aberration observed in senile plaques might be involved in amyloidogenesis in Alzheimer's disease.

Alzheimer Disease↗
PubMed1995

Differential vulnerability of calbindin-immunoreactive neurons in HIV encephalitis.

Recent studies have suggested that the neuronal damage during human immunodeficiency virus encephalitis (HIVE) might be mediated by increased intracellular calcium. Since in vitro studies have shown that calcium-binding proteins protect neurons from calcium-mediated toxicity, we hypothesized that calbindin-expressing neurons might be resistant to HIV1-mediated damage. We compared patterns of calbindin immunoreactivity in the cortex and subcortex of autopsied AIDS cases with and without HIVE. Calbindin-immunoreactive neurons in the neocortex were significantly reduced in HIVE (one-way ANOVA, p < 0.001), while these neurons in the basal ganglia and hippocampus were unaffected. The loss of calbindin-immunolabeled neurons in the neocortex was correlated with viral burden (r = -0.45, p < 0.001). Differential loss of calbindin-immunoreactive neurons in HIVE suggests that neuronal damage in different regions of the CNS may be mediated by different pathogenic mechanisms.

Basal Ganglia↗
PubMed1994

Cytokine receptor alterations during HIV infection in the human central nervous system.

Cytokines are potent factors mediating interactions between the immune and nervous systems. Cytokines released by macrophages/microglia, the predominant immune cell within the brain, have been proposed to modulate neuronal survival and death. In human immunodeficiency virus-encephalitis (HIVE), cytokines could modulate neurologic damage if nervous system cells possessed appropriate receptors. We hypothesized that the populations of neurons vulnerable to the toxic effects of cytokines in HIVE might contain specific receptors for these molecules. We examined the distribution of cytokine receptors in the human brain utilizing fluorescent-labeled cytokines combined with confocal laser microscopy imaging. Phycoerythrin-conjugated interleukin-1 beta and phycoerythrin-Avidin/biotin conjugated transforming growth factor beta 1 labeled dendritic processes of neurons in the neocortex. Labeling was abolished by pre-incubation with unlabeled cytokines. In cases with moderate HIVE, an average 35% increase in intensity of labeling was observed compared to cases without HIVE or with cases with severe HIVE. The patterns of interleukin 2 labeling were not altered in HIVE. These results suggest that neurons susceptible to cytokine-mediated damage during the progression of HIVE display abnormal patterns of cytokine receptor labeling.

AIDS Dementia Complex↗
PubMed1993

Phorbol ester-induced neuritic alterations in the rat neocortex. Structural and immunocytochemical studies.

In order to explore the effect of aberrant sprouting in the CNS, phorbol 12-myristate 13-acetate (PMA) was administered into the neocortex of adult rats. PMA is a growth-promoting agent that activates and eventually downregulates protein kinase C (PKC), and induces in the rat the expression of several genes, including amyloid precursor protein (APP). We found that multiple injections of 100 nM PMA into the rat neocortex promote, in the first week postinjection, a widespread vacuolization of the neuropil with a subsequent disruption of the synapses in the injection site, followed, at d 15, by the formation of abnormally distended clusters of neurites that resembled aberrant, sprouting axons. At d 30, fewer aberrant sprouts were observed, and many degenerating neurites were found. At the ultrastructural level, the PMA-induced abnormal neurites at d 7-15 resembled growth cones, whereas the dystrophic neurites at d 30 contained abundant dense and laminated bodies. Immunohistochemical analysis indicated that the abnormal neurites in the areas of denervation and PMA administration were positive with antisynaptophysin and antigrowth-associated protein 43 (GAP-43), with an increased APP immunoreactivity surrounding them. APP immunoreactivity around the injection site was mostly associated with pyramidal neurons and glial cells. Control experiments, where saline alone or 4 alpha-phorbol 12, 13-didecanoate (PDD, an inactive phorbol derivative) was injected, failed to show aberrant sprouting neurites. Further immunohistochemical analysis showed that the PMA-treated animals presented increased amyloid beta immunoreactivity in the pyramidal cells at the site of injection, when compared with control injections. These findings suggest that aberrant sprouting induced by overstimulation could be followed by neurodegeneration. Alternatively, PKC downregulation could directly induce the neurodegeneration, with a secondary sprouting response.

Amyloid↗
PubMed1993

Detection of Borrelia burgdorferi in tissues of experimentally infected Peromyscus leucopus by the polymerase chain reaction.

A polymerase chain reaction (PCR) assay was used to amplify a 158 base pair (bp) DNA fragment from the ospA locus of Borrelia burgdorferi. This assay could identify all of four distinct B. burgdorferi isolates from Oklahoma and could detect as little as 50 x 10(-15) g of purified DNA from B. burgdorferi (JD-1) after agarose gel electrophoresis and ethidium bromide staining. The assay was used to detect the Lyme spirochete in the heart, liver, spleen, kidney and urinary bladder of four experimentally infected Peromyscus leucopus and results were compared with detection by in vitro cultivation in BSK-II media. Fifteen of twenty organs examined showed 158 bp amplification products. Except for one kidney sample all organs that were culture-positive were also positive by PCR. Two culture-negative heart samples and one culture-negative liver sample were PCR positive. The results indicate that this PCR assay may be useful for detection of B. burgdorferi from field-caught wildlife hosts in epidemiological investigations.

Animals↗