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Biomedical subjects

X Ge

Publications and source records attributed to X Ge.

At least 19 recordsLinked to original sources

Pharmacological rescue of noise induced hearing loss using N-acetylcysteine and acetyl-L-carnitine.

Despite the use of hearing protection devices (HPDs) and engineering changes designed to improve workspaces, noise-induced hearing loss continues to be one of the most common and expensive disabilities in the US military. Many service members suffer acoustic trauma due to improper use of HPDs, sound levels exceeding the protective capacity of the HPDs, or by unexpected, injurious exposures. In these cases, there is no definitive treatment for the hearing loss. This study investigated the use of the pharmacological agents N-acetylcysteine and acetyl-L-carnitine after acoustic trauma to treat cochlear injury. N-Acetylcysteine is an antioxidant and acetyl-L-carnitine a compound that maintains mitochondrial bio-energy and integrity. N-Acetylcysteine and acetyl-L-carnitine, respectively, significantly reduced permanent threshold shifts and hair cell loss compared to saline-treated animals when given 1 and 4 h post-noise exposure. It may be possible to obtain a greater therapeutic effect using these agents in combination or at higher doses or for a longer period of time to address the secondary oxidative events occurring 7-10 days after acute noise exposure.

Acetylcarnitine↗

Antibodies to liver sinusoidal endothelial cells modulate immune responses in liver transplantation.

AIM: Liver sinusoidal endothelial cells (LSECs) have been implicated to play a role in the induction of liver allograft rejections. Here, we studied the clinical consequences of preformed LSEC-reactive antibodies and their functional capacity in modulating T-cell responses. METHODS: Pre- and posttransplant sera and T lymphocytes from 95 liver transplant patients were used in this study. LSECs were isolated from a normal healthy liver. Binding of antibodies to LSECs was detected using flow cytometric analysis. To study whether LSEC antibodies facilitated cell-mediated immunity, a mixed cell culture (MCC) assay was used. Cytokines in the supernatant of MCC were also measured by enzyme-linked immunosorbent assay. Immunohistochemical staining on liver biopsy sections was performed to detect deposition of immunoglobulins in LSEC during rejections. RESULTS: Significantly higher numbers of patients with rejections had LSEC antibodies (35/50, 70%) compared with 8/45 (18%) without rejections (P < .0001). Purified fractions of LSEC antibodies induced the expression of the costimulatory marker CD86 on LSECs. Significantly higher numbers of patients with LSEC antibodies and rejections had an increased proliferation of T cells and markedly decreased levels of transforming growth factor (TGF)-beta in the MCC as compared with those without antibodies and rejections (P < .0001, P < .0001, respectively). Deposition of antibodies in LSECs during rejection episodes was observed in the biopsies of patients with LSEC antibodies but not in those without LSEC antibodies. CONCLUSION: Our data suggest that antibodies to LSEC may facilitate acute liver allograft rejections by down-regulating the immune modulating cytokine TGF-beta and thus up-regulating alloreactive T-cell proliferation.

Antibody Formation↗

DNA vaccination with an insulin construct and a chimeric protein binding to both CTLA4 and CD40 ameliorates type 1 diabetes in NOD mice.

Type 1 diabetes (T1D), a T-cell-mediated autoimmune disease, could be attributed to many defects in nonobese diabetic (NOD) mice, including deficient expressions of costimulatory molecules that impair antigen presentation. Thus, this deficient antigen presentation may result in a reduced ability to induce a tolerogenic response through negative selection/regulation of autoreactive T cells. Improperly activated T cells seem to be able to induce autoimmune responses causing diabetes. To re-establish tolerance to autoantigens by modulating costimulation, we constructed and tested a new type of DNA vaccine encoding a membrane-bound preproinsulin (mbPPI) and a chimeric gene vector encoding mutant B7.1/CD40L (mB7.1/CD40L) fusion protein. This mutant B7.1 binds CTLA4 but not CD28. We report that young NOD mice immunized with mbPPI along with mB7.1/CD40L DNA vectors significantly reduced diabetes incidence while treatment with CTLA4/IgG1 exacerbated diabetes. In conclusion, the combination of mbPPI and mB7.1/CD40L was able to protect against autoimmunity and diabetes in NOD mice possibly by promoting a more efficient presentation of autoantigen PPI and inducing specific tolerance to PPI by negatively regulating autoreactive T cells.

Animals↗

Stachyose extract from Rehmannia glutinosa Libosch. to lower plasma glucose in normal and diabetic rats by oral administration.

The hypoglycemic effects of water extract and stachyose extract (Part III) from Rehmannia glutinosa Libosch. were investigated in this paper by oral administration to normal, glucose- and adrenaline-induced hyperglycemic and alloxan-induced diabetic rats. The results showed that Part III had the effect of lowering fasted plasma glucose level and partially preventing hyperglycemia induced by glucose (2.5 g x kg(-1), i.p.) and adrenaline (300 microg x kg(-1), i.p.), respectively, but no obvious dose-dependent effect was found when it was administered at the doses of 100, 200 and 400 mg x kg(-1) for 6 days, i.g. In alloxan-induced diabetic rats, Part III (200 mg x kg(-1) for 15 days, i.g.) gave a significant decrease in blood glucose level. The results suggested that Part III, which is mainly composed of stachyose from Rehmannia glutinosa Libosch., had a significant hypoglycemic effect in glucose- and adrenaline-induced hyperglycemic and alloxan-induced diabetic rats.

Administration, Oral↗

Environmental nano-pollutants (ENP) and aquatic micro-interfacial processes.

The concepts of nano-science and technology are penetrating into the aspects of environmental science and technology. Environmental nano-pollutants (ENP) is suggested. as a specific category of pollutants that presents many common critical characters impacting the natural and social ecosystems. The outstanding properties are the various reactions in the macro-interfacial processes. Several examples as the adsorption of rare-earth metals on Chinese loess, the adsorption of PAHs on aquatic sediments with humic substances and the speciation of nano-flocculants in the water and wastewater treatment are discussed in the paper.

Adsorption↗

Viruses in subgroup 2 of the genus Ilarvirus share both serological relationships and characteristics at the molecular level.

Sequence data have been determined for 5 members of subgroup 2 of the genus Ilarvirus. These data support the known serological relationships among accepted members of this group and indicate that the ilarvirus Hydrangea mosaic virus (HdMV) is an isolate of Elm mottle virus (EMoV). The close relationships between members of this subgroup, exhibited through the coat proteins coded on RNA 3, extend to the other genomic molecules. Primers designed from the sequences of RNA 1 and RNA 2 of EMoV amplified fragments from all other subgroup 2 viruses but not from other ilarviruses. Although closely related, members of this subgroup occur naturally in distinctly different host species. The possible origins of the viruses are discussed in relation to similarities among the genomic molecules, in particular RNA 3.

Amino Acid Sequence↗

Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and their soluble receptors in coal workers' pneumoconiosis.

The aim of this study was to investigate whether systemic tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors (p55, p75), interleukin 6 (IL-6), and soluble IL-6 receptor could be markers of biological activities of coal workers' pneumoconiosis (CWP). The study population was composed of 182 Chinese retired coal miners who had similar dust exposure histories. Among them, 71 were cases with CWP and 111 were controls. Chest radiographs were classified according to International Labour Organization Criteria (ILO, 1980). Individual dust exposure variables were estimated from work histories, and smoking information was obtained from interviews. Serum concentrations of TNF-alpha, TNF-alpha receptors (p55, p75), IL-6, and IL-6 receptor were measured by ELISA techniques. Mean serum levels of p55, p75 and IL-6 were significantly higher in cases than in controls (P < or = 0.01 for each comparison by crude analyses). Results from logistic regression models, adjusted for age, dust exposure variables, and smoking habits, found similar associations between soluble p55 and p75 levels and the presence of CWP. Linear regression analysis revealed that CWP radiographic stage (by ILO criteria) was significantly correlated with the individual serum concentrations of p55, p75 and IL-6. Serum concentrations of all measured cytokines were notcorrelated to age, dust exposure, or smoking, but there were correlations between soluble p75 and p55 levels, and between p75 and IL-6 levels. The results of this study suggest that serum levels of TNF receptors and IL-6 are associated with the fibrotic process of CWP and serum cytokine levels may be correlated with the severity of CWP.

Aged↗

A strategy for the determination of enzyme kinetics using electrospray ionization with an ion trap mass spectrometer.

A simple and rapid means of enzyme kinetic analysis was achieved using electrospray ionization mass spectrometry and a one-point normalization factor. The model system used, glutathione S-transferase from porcine liver, is a two-substrate enzyme catalyzing the conjugation of glutathione with a variety of compounds containing an electrophilic center. An internal standard that is structurally similar to the product was added to the reaction quench solution, and a single-point normalization factor was used to determine the product concentration without the need of a calibration curve. Kinetic parameters, such as Km, Vmax and Ki (for thyroxine), obtained by electrospray mass spectrometry agreed with those obtained from traditional UV-vis spectroscopy, and competitive vs noncompetitive inhibition reactions could be delineated via mass spectrometry. These results suggest that our method can be applied to enzymatic processes in which spectrophotometric or spectrofluorometric assays are not feasible or when the relevant substrates do not incorporate chromophores or fluorophores. This new method is competitive with traditional UV assays in that it is facile and it involves very little analysis time.

Animals↗

Evidence for involvement of the neural pathway containing the peripheral vagus nerve, medullary visceral zone and central amygdaloid nucleus in neuroimmunomodulation.

It is now evident that a bidirectional communication network exists between the central nervous system (CNS) and immune system (IS). However, the way in which the IS passes inform to the brain is not quite clear.In the present study, one of the neural pathways involved in the cytokine-to-brain communication was investigated in the rat. This pathway starts at the vagal nerve projecting to the medullary visceral zone (MVZ), an arc-shape band from the dorsomedial to ventrolateral area in the middle-caudal segment of the medulla oblongata, and terminates at the central amygdaloid nucleus (Ce) which receives projections from large catecholaminergic neurons in the MVZ. Animals were randomly divided into two experimental groups. Triple-labeling was used in Group I animals to combine wheat germ aggulutinin-conjugated horseradish peroxidase (WGA-HRP) retrograde tracing with anti-Fos and anti-tyrosine hydroxylase (TH) immunostaining. WGA-RP was stereotaxically injected into the unilateral Ce of the animals and, after a survival period of 48 h, intraperitoneal (IP) injection of lipopolysaccharide (LPS) was performed. Seven kinds of labeled neurons were observed in the MVZ, namely, HRP-, Fos- or TH-singly-labeled neurons; Fos/HRP-, Fos/TH- or HRP/TH-doubly-labeled neurons; and Fos/HRP/TH-triply-labeled neurons. As for Group II animals, bilateral subdiaphragmatic vagotomy (SDV) or sham operation was performed, followed 4 weeks later by IP injection of LPS. The number of Fos-positive neurons within the Ce and MVZ was significantly lower (P<0.01) in rats having SDV when compared with those receiving sham operation. Our results suggest that part of the peripheral immune information can be conveyed through the vagus to the catecholaminergic neurons in the MVZ, where it is transported to the Ce. The MVZ is a neural relay station in the immune-to-brain communication and might play a significant role in neuroimmuno-modulation via the vagus-MVZ-Ce pathway.

Amygdala↗

Attenuation of morphine dependence and withdrawal in rats by venlafaxine, a serotonin and noradrenaline reuptake inhibitor.

The effects of venlafaxine, a novel serotonin and adrenaline reuptake inhibitor, on the morphine withdrawal and activation of morphine conditioned place preference (CPP), were investigated in rats. Our results showed that the most morphine withdrawal signs, including jumping, writhing, shakes, exploring, lacrimation, piloerection, irritability, and diarrhea, were attenuated by pretreatment with 10 or 20 mg/kg venlafaxine. To investigate the effects of venlafaxine on relapse to opiate dependence, the morphine CPP was used and a dopamine D2 antagonist sulpiride was selected as a control drug. The morphine CPP disappeared following a 28-day drug-free period and appeared again after given a single injection of 1 mg/kg morphine. Acute treatment with sulpiride (25 or 50 mg/kg, i.p.) 30 min prior to 1 mg/kg morphine injection significantly blocked the reacquisition of CPP, while venlafaxine (10 or 20 mg/kg, i.p.) did not show significant effect. However, chronic treatment with venlafaxine (5 or 10 mg/kg, i.p. twice, daily, for seven consecutive days) significantly attenuated the reacquisition of morphine CPP, whereas chronic treatment with sulpiride (10 or 20 mg/kg, i.p.) have no significant effect. Our results demonstrated for the first time that venlafaxine strongly attenuates morphine withdrawal and morphine-induced reaquisition of

Adrenergic Uptake Inhibitors↗

Pubertal transition, stressful life events, and the emergence of gender differences in adolescent depressive symptoms.

This study examined the role of both pubertal and social transitions in the emergence of gender differences in depressive symptoms during adolescence. This study generated the following findings: (a) Gender differences in depressive symptoms emerged during 8th grade and remained significant through 12th grade. (b) Pubertal status in 7th grade was related to adolescent depressive symptoms over time. (c) Early-maturing girls represented the group with the highest rate of depressive symptoms. (d) Depressive symptoms measured in 7th grade predicted subsequent symptom levels throughout the secondary school years. (e) Recent stressful life events were associated with increased depressive symptoms. (f) Early-maturing girls with higher levels of initial symptoms and more recent stressful life events were most likely to be depressed subsequently. The findings demonstrate the importance of the interaction between the pubertal transition and psychosocial factors in increasing adolescent vulnerability to depressive experiences.

Adolescent↗

Linking parenting processes and self-regulation to psychological functioning and alcohol use during early adolescence.

A longitudinal transactional model was tested linking parenting and youth self-regulation to youths' psychological functioning and alcohol-use behavior. Participants included one hundred twenty 12-year-olds, their mothers, and their fathers from whom three waves of data were collected at 1-year intervals. Teachers provided assessments of self-regulation, and parenting was assessed from multiple perspectives, including youth reports, parent reports, and observer ratings. Youths reported their psychological functioning and alcohol-use behavior. The data supported the model. Parenting and youth self-regulation were stable across time, and self-regulation was linked with changes in harsh-conflicted parenting from Wave 1 to Wave 2. Parenting at Wave 2 was associated with youth self-regulation. Youth self-regulation at Wave 2 mediated the paths from parenting practices at Wave 2 to youth psychological functioning and alcohol use at Wave 3.

Adaptation, Psychological↗

Specific amino acid deficiency alters the expression of genes in human melanoma and other tumor cell lines.

This study determined the effect of tyrosine (Tyr) and phenylalanine (Phe) deprivation on protein expression and phosphorylation of mitogen-activated protein kinase kinase 4 (MKK4)/stress-activated protein/Erk kinase (SEK1), a metastasis suppressor gene. Differential display and suppressive subtractive hybridization techniques identified genes modulated by Tyr and Phe deprivation. Expression of MKK4/SEK1 protein varied widely among human A375, A375SM and SB2 melanoma, PC-3 and DU145 prostate cancer, and MDA-MB-231 breast cancer cell lines and within the different lines. Phosphorylation of the MKK4/SEK1 protein similarly varied. No differences in MKK4/SEK1 gene expression or in the 41 other metastasis and tumor suppressor genes were found in A375 melanoma cells cultured in Tyr- and Phe-deprived media. A number of up-regulated and down-regulated genes in A375 melanoma cells were identified by differential display and suppressive subtractive hybridization that were pertinent to regulation of cytoskeletal organization, cell movement, gene transcription and metastasis. Two tumor marker genes, the gene for enolase and FUS/CHOP, were down-regulated by Tyr and Phe deprivation. This study shows that tumor cells display heterogeneity in their response to deprivation of Tyr and Phe and that these amino acids may be signaling molecules that regulate gene expression and function in tumor cells.

Blotting, Western↗

Delayed facial palsy after stapedectomy.

OBJECTIVE: To study the incidence, pathogenesis, and prevention of delayed facial palsy after stapedectomy. STUDY DESIGN: Retrospective case review. SETTING: Otology/neurotology referral center. PATIENTS: A series of 2152 stapedectomy procedures in 2106 patients over 12 years. INTERVENTION: Delayed facial palsy after stapedectomy was studied. MAIN OUTCOME MEASURE: House-Brackmann facial nerve grading system and serum antibody titer tests for herpes simplex virus type I and type II, and varicella zoster virus. RESULTS: Delayed facial palsy occurred in 11 of 2152 procedures. Delayed facial palsy occurred from 5 to 16 days (mean 8) after stapedectomy. Predisposing factors were bony facial canal dehiscence with bare or bulging facial nerve herniation in 5 patients; chorda tympani nerve stretched, manipulated, or cut in 2 patients; granulomatous reaction to Gelfoam in 1 patient; fever blisters on the upper lip in 1 patient; and sinusitis in 2 patients. Elevated anti-varicella antibody titers were found in all 6 patients studied. Anti-herpes simplex type I and II antibody titers were elevated in 5 of 6 patients. Acyclovir was effective in preventing delayed facial palsy in 1 patient who had undergone revision stapedectomy and experienced delayed facial palsy after previous stapedectomy in the same ear with elevated anti-herpes antibody titer. CONCLUSIONS: Delayed facial palsy occurred in 0.51% of patients after stapedectomy. Serologic investigation suggests activation of latent herpesvirus. Mechanical irritation of the facial or chorda nerve during operation may trigger the activation. The anti-herpesvirus agent acyclovir may prevent delayed facial palsy after stapedectomy in patients suspected of having this complication.

Adult↗

Presence of autoantibodies in the sera of Meniere's disease.

We examined the sera of patients with Meniere's disease for the presence of antibodies against 8 inner ear antigens by enzyme-linked immunosorbent assay (ELISA). One hundred eight patients with Meniere's disease and 28 control subjects were studied. The antibodies against chicken type II collagen, bovine type II collagen, the cyanogen bromide cleaved peptide 11 (CB11) of each, type IX and XI collagens, C-Raf, and tubulin were measured by ELISA. The sensitivity of each antigen was between 37% and 60% individually, and was 91% when all 8 inner ear antigens were combined. These results showed that 91% of Meniere's disease sera have antibody activities to 1 or more of these inner ear antigens. The results suggest that performing ELISA for these 8 inner ear antigens was useful as a diagnostic tool for Meniere's disease. Further study is required for elucidating the role of these antigens in the pathogenesis of Meniere's disease, which might eventually result in better therapy.

Autoantibodies↗