PubMed Health⌕ Search

Biomedical subjects

H Lian

Publications and source records attributed to H Lian.

6 recordsLinked to original sources
PubMed2004

CD8alpha dendritic cells and immune protection from experimental allergic encephalomyelitis.

Dendritic cells (DC) represent a phenotypically heterogeneous population endowed with two important biological functions, immunity and tolerance. Here we report that the injection of splenic CD8alpha(+) DC, derived from rats with experimental allergic encephalomyelitis (EAE), delayed the onset and suppressed the severity of EAE in Lewis rats. This was accompanied by the lack of magnetic resonance imaging (MRI) lesions in the brain and spinal cord and by reduced numbers of inflammatory cells within the central nervous system. Injection of CD8(alpha+) DC inhibited T cell proliferation that may relate to increased interferon (IFN)-gamma and nitric oxide production. Although CD8(+)CD28(-) suppressor T cells, apoptotic cells and co-stimulatory molecules were not altered, CD4(+) T cells expressing interleukin (IL)-10 were augmented in rats receiving CD8alpha(+) DC compared to rats receiving total DC or medium. These results demonstrate that rat splenic CD8alpha(+) DC could provide a cellular basis for a novel, individualized immunotherapy using autologous DC as a complement to conventional therapy in diseases with an autoimmune background such as multiple sclerosis.

Animals↗
PubMed2004

Interferon-gamma-modified dendritic cells suppress B cell function and ameliorate the development of experimental autoimmune myasthenia gravis.

This study was designed to investigate the therapeutic effects of interferon (IFN)-gamma-modulated dendritic cells (DC) in experimental autoimmune myasthenia gravis (EAMG). We induced EAMG in Lewis rats by immunization with Torpedo nicotinic acetylcholine receptor (nAChR) and adjuvant. On day 33 post-immunization (p.i.), splenic DC were prepared, exposed to IFN-gamma alone (IFN-gamma-DC) or to IFN-gamma in combination with 1-methyl-DL-tryptophan (1-MT), the specific inhibitor of indoleamine 2,3-dioxygenase (IDO) (IFN-gamma + 1-MT-DC), and injected subcutaneously into rats with incipient EAMG on day 5 p.i. A control group of EAMG rats received naive DC on day 5 p.i., while another group received 1-MT every other day, intraperitoneally (p.i.), from days 5 to 41 p.i. The severity of clinical signs of EAMG was reduced dramatically in IFN-gamma-DC-treated rats compared to rats receiving naive DC, IFN-gamma + 1-MT-DC or 1-MT alone. The number of plasma cells secreting nAChR antibodies was reduced and the expression of B cell activation factor (BAFF) on splenic and lymph node mononuclear cells (MNC) was down-regulated in rats treated with IFN-gamma-DC. In vitro co-culture of MNC derived from EAMG rats with IFN-gamma-DC produced relatively few cells secreting nAChR antibodies. Addition of 1-MT to the co-culture significantly increased the number of cells secreting nAChR antibodies. We conclude that IFN-gamma-DC reduced the number of plasma cells secreting nAChR antibodies in an IDO-dependent manner and ameliorated the development of EAMG in Lewis rats.

Animals↗
PubMed2001

Disruption of the Cockayne syndrome B gene impairs spontaneous tumorigenesis in cancer-predisposed Ink4a/ARF knockout mice.

Cells isolated from individuals with Cockayne syndrome (CS) have a defect in transcription-coupled DNA repair, which rapidly corrects certain DNA lesions located on the transcribed strand of active genes. Despite this DNA repair defect, individuals with CS group A (CSA) or group B (CSB) do not exhibit an increased spontaneous or UV-induced cancer rate. In order to investigate the effect of CSB deficiency on spontaneous carcinogenesis, we crossed CSB(-/-) mice with cancer-prone mice lacking the p16(Ink4a)/p19(ARF) tumor suppressor locus. CSB(-/-) mice are sensitive to UV-induced skin cancer but show no increased rate of spontaneous cancer. CSB(-/-) Ink4a/ARF(-/-) mice developed 60% fewer tumors than Ink4a/ARF(-/-) animals and demonstrated a longer tumor-free latency time (260 versus 150 days). Moreover, CSB(-/-) Ink4a/ARF(-/-) mouse embryo fibroblasts (MEFs) exhibited a lower colony formation rate after low-density seeding, a lower rate of H-Ras-induced transformation, slower proliferation, and a lower mRNA synthesis rate than Ink4a/ARF(-/-) MEFs. CSB(-/-) Ink4a/ARF(-/-) MEFs were also more sensitive to UV-induced p53 induction and UV-induced apoptosis than were Ink4a/ARF(-/-) MEFs. In order to investigate whether the apparent antineoplastic effect of CSB gene disruption was caused by sensitization to genotoxin-induced (p53-mediated) apoptosis or by p53-independent sequelae, we also generated p53(-/-) and CSB(-/-) p53(-/-) MEFs. The CSB(-/-) p53(-/-) MEFs demonstrated lower colony formation efficiency, a lower proliferation rate, a lower mRNA synthesis rate, and a higher rate of UV-induced cell death than p53(-/-) MEFs. Collectively, these results indicate that the antineoplastic effect of CSB gene disruption is at least partially p53 independent; it may result from impaired transcription or from apoptosis secondary to environmental or endogenous DNA damage.

Age Factors↗
PubMed2000

A self-complementary, self-assembling microsphere system: application for intravenous delivery of the antiepileptic and neuroprotectant compound felbamate.

Felbamate (FBM) is a novel antiepileptic drug (AED) and neuroprotectant (NP) compound that interacts with strychnine-insensitive (SI) glycine receptors in brain (IC(50) = 374 microM). FBM concentrations required to interact with SI glycine receptors are consistent with brain levels following oral and intraperitoneal administration of AED and NP doses. Because of the solubility limits of FBM, an intravenous (iv) form has not been developed. Nevertheless, an iv form could be important for the treatment of disorders such as status epilepticus and neuronal damage due to hypoxic/ischemic events. Substituted diketopiperazines precipitate in acid to form microspherical particles of uniform size ( approximately 2 microm). The microsphere system entraps drugs on precipitation and dissolves near physiological pH to release the drug cargo. Therefore, microspheres were used to produce an iv formulation of FBM. Mice were administered the FBM/microsphere (20-60 mg/kg FBM) and tested for protection against tonic extension seizures using maximal electroshock. The FBM/microsphere was effective in a time- and dose-dependent manner following iv administration. The median effective dose (ED(50)) for protection against MES seizures at 30 min was 27.2 mg/kg [95% confidence interval (CI) = 20.8-33.4, slope = 6.5]. The ED(50) for minimal motor impairment at 30 min was 167 mg/kg (95% CI = 155-177, slope = 28.1). Thus, the feasibility of encapsulating FBM or similar aqueous insoluble compounds in a microsphere system with delivery by the iv route for treatment of epilepsy and various central nervous system disorders has been clearly demonstrated. Studies were performed in accordance with the Guide for the Care and Use of Laboratory Animals.

Animals↗
PubMed1993

[Malonaldehyde, superoxide dismutase and human cataract].

UV-spectrophotometry and fluorometry were used to study Malonaldehyde (MDA) and Superoxide Dismutase (SOD) in normal, cataractous human lenses and red blood cells of the patients with cataract. MDA content of senile and complicated cataractous lenses was significantly higher than that of normal human lenses, while that of complicated cataract was significantly higher than that of senile cataract. SOD activity of senile and complicated cataractous lenses was significantly lower than that of normal human lenses, while there was no marked difference between senile and complicated cataractous lenses. Significant correlation between cataractous lenses and red blood cells was not found in MDA content and SOD activity. There was a negative correlation between SOD and MDA in normal human lenses, but no correlation between SOD and MDA in cataractous lenses. The study shows that lipid peroxidation may be one of the possible mechanisms of cataractogenesis in human, and emphasizes the role of SOD in prevention of photoperoxidative damages to the tissues.

Adult↗