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Biomedical subjects

L Y Yu

Publications and source records attributed to L Y Yu.

At least 19 recordsLinked to original sources
PubMed2001

Interleukin 10 aggravates experimental autoimmune myasthenia gravis through inducing Th2 and B cell responses to AChR.

The damage of acetylcholine receptor (AChR) at neuromuscular junctions of experimental autoimmune myasthenia gravis (EAMG), an animal model of human MG, is mediated by B cells which require T cell help. The Th2 associated cytokine IL-10 suppresses production of cytokines released by Th1 cells and is considered for treatment of human autoimmune diseases. To evaluate the role of IL-10 in EAMG, rhIL-10 was administered daily to Lewis rats by the subcutaneous route starting at the day of immunization and continued for 7 weeks. IL-10 failed to abrogate EAMG at low dose (0.1 or 1 microg/day) and at the dose of 3 microg/day caused earlier onset and aggravated clinical signs of EAMG when compared to EAMG rats injected with PBS only. Although Th1 responses reflected by AChR-induced lymphocyte proliferation and levels of IFN-gamma secreting cells, as well as AChR-induced Th1 cytokine mRNA expression was suppressed, augmented IL-4 mRNA expression and AChR-specific B cell responses may play an important role in the failure of IL-10 to abrogate EAMG. This study implicates a critical precaution in planning immunotherapy of IL-10 in antibody-mediated autoimmune diseases, e.g. MG.

Acetylcholine↗
PubMed2001

Neuron-specific Bcl-2 homology 3 domain-only splice variant of Bak is anti-apoptotic in neurons, but pro-apoptotic in non-neuronal cells.

We have identified and characterized N-Bak, a neuron-specific isoform of the pro-apoptotic Bcl-2 family member Bak. N-Bak is generated by neuron-specific splicing of a novel 20-base pair exon, which changes the previously described Bak, containing Bcl-2 homology (BH) domains BH1, BH2, and BH3, into a shorter BH3-only protein. As demonstrated by reverse transcription-polymerase chain reaction and RNase protection assay, N-Bak transcripts are expressed only in central and peripheral neurons, but not in other cells, whereas the previously described Bak is expressed ubiquitously, but not in neurons. Neonatal sympathetic neurons microinjected with N-Bak resisted apoptotic death caused by nerve growth factor (NGF) removal, whereas microinjected Bak accelerated NGF deprivation-induced death. Overexpressed Bak killed sympathetic neurons in the presence of NGF, whereas N-Bak did not. N-Bak was, however, still death-promoting when overexpressed in non-neuronal cells. Thus, N-Bak is an anti-apoptotic BH3-only protein, but only in the appropriate cellular environment. This is the first example of a neuron-specific Bcl-2 family member.

Alternative Splicing↗
PubMed2000

[The bacteria detection and drug sensitivity test from infected root canals].

OBJECTIVE: To provide bacteriological basis for curing infected root canals with sensitive drugs. METHODS: We have made bacterial cultivation for 56 cases with infected root canals and drug sensitive test with agar dilution. RESULTS: The rates of bacteria detection and positive rates from infected root canals were high. Anaerobia and aerobia were sensitive to different kinds of antibiotics. CONCLUSION: Bacteria have close relation to infected root canals. Sensitive drugs should be selected in clinical treatment.

English Abstract↗
PubMed1999

The role of LY49 NK cell subsets in the regulation of murine cytomegalovirus infections.

The distributions and functions of NK cell subsets, as defined by the expression of Ly49 NK cell receptors, were examined in murine CMV (MCMV)-infected mice. MCMV induced a reduction in NK1.1+ cell number in the spleen and an increase in the peritoneal exudate cells. Within the splenic NK1.1+ population, proportional increases in Ly49A+ and Ly49G2+ cells but decreases in Ly49C+ and Ly49D+ cells were observed 3 days post-MCMV infection, but within the peritoneal NK1.1+ cell populations there were proportional decreases in Ly49A+ cells and increases in Ly49C+, Ly49D+, and Ly49G2+ cells. Lymphocytic choriomeningitis virus did not elicit a comparable NK cell subset distribution. Lymphokine-activated killer cells were sorted into different Ly49 NK cell subsets and adoptively transferred into C57BL/6 suckling mice. Regulation of MCMV synthesis in these suckling mice was shown to be an IFN-gamma-dependent, perforin- and Cmv-1-independent process, and each NK cell subset mediated anti-viral activity. In adult C57BL/6 mice, the control of MCMV in the spleen is mediated by a perforin-dependent mechanism, regulated in part by the Cmv-1 gene, which maps closely to the Ly49 family. In vivo depletions of either one or two of the Ly49 subsets in adult mice did not affect the ability of the residual NK cells to regulate MCMV synthesis. These data provide evidence of NK cell subset distribution and function in MCMV infection, but no individual subset was required for the Cmv-1-like regulation of MCMV synthesis.

Adoptive Transfer↗
PubMed1998

Synthetic peptides fail to induce nasal tolerance to experimental autoimmune myasthenia gravis.

Nasal administration of Torpedo acetylcholine receptor (AChR) to Lewis rats prior to induction of experimental autoimmune myasthenia gravis (EAMG) is highly efficient in prevention of clinical weakness, and suppression of AChR-specific T and B cell responses. To identify possible antigenic determinants within the receptor which can modulate EAMG and anti-AChR response, we evaluated the effects of nasal administration of alpha 61-76, alpha 100-116, alpha 146-162, delta 354-367, and alpha 261-277 of Torpedo AChR at different doses on the tolerance induction against EAMG irrespective if given at lower, the same or higher doses than whole Torpedo AChR protein, that was confirmed to be highly efficient as tolerogen to EAMG. None of these peptides, neither administrated alone nor in combination, induced tolerance to EAMG. Peptide administration did not affect the levels or affinities of anti-AChR antibodies when compared with non-tolerized control EAMG rats, while administration of whole AChR protein affected both variables. The results may indicate that the T and B cell heterogeneity of AChR epitopes makes it difficult to induce tolerance using synthetic peptide.

Animals↗
PubMed1998

Oltipraz chemoprevention trial in Qidong, People's Republic of China: modulation of serum aflatoxin albumin adduct biomarkers.

In 1995, 234 adults from Qidong, People's Republic of China, were enrolled and followed in a Phase IIa 4-methyl-5-(N-2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz) chemoprevention trial. Residents of this area are at high risk for development of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated foods. The intervention was a randomized, placebo-controlled, double-blind study. Elements of the study design and clinical outcomes have been recently published (Jacobson et al, Cancer Epidemiol. Biomark. Prev., 6: 257-265, 1997). The primary objective was to conduct a preliminary assessment of the ability of oltipraz to modulate levels of a validated biomarker of aflatoxin exposure and of the risk of hepatocellular carcinoma by determining levels of aflatoxin-albumin adducts in sera. Healthy eligible individuals were randomized into three arms to receive p.o. 125 mg of oltipraz daily, 500 mg of oltipraz weekly, or placebo for 8 weeks. There were no consistent changes in biomarker levels in the placebo arm over the 16-week observation period, nor was any apparent effect observed in the arm receiving 125 mg of oltipraz each day. However, individuals receiving 500 mg of oltipraz once a week for 8 weeks showed a triphasic response to oltipraz. No effect was observed during the 1st month of the intervention, whereas a significant (P = 0.001) diminution in adduct levels was observed during the 2nd month of active intervention and during the lst month of follow-up. A partial rebound in adduct levels toward baseline values was observed during the 2nd month postintervention. Linear regression models up to week 13 confirmed a significant (P = 0.008) weekly decline of biomarker levels in the group receiving 500 mg of oltipraz once a week. However, despite these effects relative to baseline values within the 500-mg weekly arm, there were no statistically significant differences in biomarker trajectories between treatment arms. The genotype for glutathione S-transferase M1, an oltipraz-inducible isoform involved in the detoxification of aflatoxin B1, did not appear to affect either baseline levels or rates of decline in the biomarker. A follow-up Phase IIb trial with a longer intervention period will be necessary to determine the full extent to which aflatoxin biomarker burden can be reduced and whether diminution of biomarkers can be sustained over the long term.

Adult↗
PubMed1997

Linomide suppresses both Th1 and Th2 cytokines in experimental autoimmune myasthenia gravis.

Suppressive effects of the synthetic immunomodulatory drug Linomide have been shown in several autoimmune models, including antibody-mediated experimental autoimmune myasthenia gravis (EAMG), a model for human myasthenia gravis (MG). To define the mechanisms underlying EAMG suppression, we injected Linomide subcutaneously at different doses into Lewis rats immunized with Torpedo acetylcholine receptor (AChR) in complete Freund's adjuvant (CFA), and investigated AChR-specific T and B cell responses, and the levels of lymph node cells expressing mRNA of different cytokines after AChR stimulation in vitro. Both 160 and 16, but not 1.6, mg/kg/day of Linomide effectively suppressed clinical muscle weakness, accompanied by decreased AChR-induced T and B cell responses. Linomide also suppressed the mRNA expression of the Th1 cytokines IFN-gamma, IL-12 and TNF-alpha as well as the Th2 cytokines IL-4 and IL-10, which are important in the immunopathogenesis of EAMG by promoting antibody production. There were no differences for IL-1beta, IL-6, lymphotoxin or TGF-beta expression in Linomide-treated vs nontreated control EAMG rats. We conclude that Linomide suppresses clinical EAMG as well as B and T cell responses to AChR by counteracting the production of AChR-induced Th1 and Th2 cytokines.

Adjuvants, Immunologic↗
PubMed1997

Oltipraz chemoprevention trial in Qidong, People's Republic of China: study design and clinical outcomes.

In 1995, 234 adults from Qidong, Jiangsu Province, People's Republic of China, where hepatocellular carcinoma is the leading cause of cancer deaths and exposure to dietary aflatoxins is widespread, were enrolled and followed in a Phase II chemoprevention trial. The goals of the study were to define a dose and schedule of oltipraz for reducing levels of validated aflatoxin biomarkers and to characterize dose-limiting toxicities. Healthy eligible individuals, including those infected with hepatitis B virus, were randomized to receive either 125 mg of oltipraz daily, 500 mg of oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor toxicities and evaluate biomarkers over the 8-week intervention period and subsequent 8-week follow-up period. Unique trial aspects included a synchronous follow-up schedule, daily observed administration of all medications, timely international data transference, and use of biomarkers as outcomes. One hundred thirty-two participants took their medications without interruptions, approximately 77% contributed all nine urine samples, and 78% contributed all seven blood samples. Fifty-one participants (21.8%) reported clinical adverse events. An extremity syndrome, developing soon after the start of treatment, was the only event that occurred more frequently (P = 0.002) among the active groups (18.4 and 14.1% of the daily 125 and weekly 500 mg arms, respectively) compared with placebo (2.5%). The oltipraz arms did not differ in symptom type or severity, and there were no indications of exacerbated drug intolerance among the few participants infected with hepatitis B virus. The good compliance with an intense follow-up schedule shows that chemoprevention trials with biomarker end points may be conducted in such populations.

Adult↗
PubMed1997

Oltipraz chemoprevention trial in Qidong, Jiangsu Province, People's Republic of China.

Oltipraz has been used clinically in many regions of the world as an antischistosomal agent and is an effective inhibitor of aflatoxin hepatocarcinogenesis in rats. This chemopreventive action of oltipraz results primarily from an altered balance in aflatoxin metabolic activation and detoxication. In 1995, a randomized, placebo-controlled, double-blind intervention was conducted in residents of Qidong, People's Republic of China, who are at high risk for exposure to aflatoxin and development of hepatocellular carcinoma. The major study objectives were to define a dose and schedule for oltipraz that would reduce levels of aflatoxin biomarkers in biofluids of the participants, and to further characterize dose-limiting side effects. Two hundred thirty-four healthy eligible individuals, including those infected with HBV, were randomized to receive either 125 mg oltipraz daily, 500 mg oltipraz weekly, or placebo. Blood and urine specimens were collected to monitor potential toxicities and evaluate biomarkers over the 8-week intervention and subsequent 8-week follow-up periods. Overall, compliance in the intervention was excellent; approximately 85% of the participants completed the study. Objective evaluation of adverse events was greatly facilitated by inclusion of a placebo arm in the study design. A syndrome involving numbness, tingling, and pain in the fingertips was the only event that occurred more frequently among the active groups (18 and 14% of the daily 125 mg and weekly 500 mg arms, respectively) compared to placebo (3%). These symptoms were reversible and could be relieved with non-steroidal antiinflammatory agents. A more complete understanding of the chemopreventive utility of oltipraz awaits completion of an assessment of the efficacy of oltipraz in modulating levels of aflatoxin biomarkers.

Animals↗
PubMed1994

[POEMS syndrome--a report of eight cases and review of literature].

POEMS syndrome is an unusual multisystem disorder associated frequently with polyneuropathy, organomegaly, endocrinopathy, M-protein change and skin lesion. POEMS is the acronym the above-mentioned clinical manifestations. The patients who were diagnosed must have at least three of the manifestations; polyneuropathy and plasmagenic disorders are almost always present. We present in this paper eight patients, their clinical symptoms, laboratory tests and treatment were analysed and discussed.

Adult↗
PubMed1994

[Effect of superoxide dismutase and diethyldithiocarbamate on the induction of squamous cell carcinoma of lung with methylcholanthrene in rats].

The squamous cell carcinoma of lung was induced with methylcholanthrene (MCA) in iodized oil in Wistar rats. During the development of the cancer, the animals were given superoxide dismutase (SOD) or its inhibitor diethyldithiocarbamate (DDC). In DDC group, 3 out of 50 rats developed cancer and 4 developed atypical hyperplasia of bronchial epithelium within 35 to 40 days. In SOD group, no cancer developed in all of the 52 rats, and only one had atypical hyperplasia in the lungs. Only one of 42 control rats had cancer and 2 rats had atypical hyperplasia of bronchial epithelium. The difference in cancer frequency between groups DDC and SOD was significant (P < 0.05). The results suggest that there is a synergism between DDC and MAC in the induction of lung cancer, while SOD can inhibit MCA-induced lung cancer development. The mechanism of the effect of SOD and DDC was discussed.

Animals↗
PubMed1992

A preliminary observation on auto-cholinergic synapse dysfunction in patients with different types of epilepsy.

Serum anti-acetylcholine receptor antibodies (A AchR Ab) and anti-synaptic premembrane antibodies (A PrM Ab) were measured in 21 patients with absence epilepsy, 21 cases with benign childhood epilepsy with centro-temporal spikes (BCECTs) and 13 cases with atypical epilepsy. Respectively, in five (23.8%), eleven (51.2%) and eight (66.7%) of the above mentioned groups of patients both A AchR Ab and A PrM Ab were found.

Adolescent↗
PubMed1981

Thyroid or glucocorticoid hormone induces pre-growth-hormone mRNA and its probable nuclear precursor in rat pituitary cells.

Thyroid or glucocorticoid hormone increases the synthesis of growth hormone (GH) by clonal lines of rat pituitary tumor cells. To investigate whether these increases arise from increased accumulation of GH-specific RNA sequences in the cytoplasm and nuclei of these cells, we adapted two existing procedures so that a 32P-labeled hybrid plasmid containing a cDNA sequence could be used to quantitate relative concentrations of the corresponding mRNA. One method (RNA gel blot hybridization) used electrophoresis of RNA, transfer to nitrocellulose paper, and hybridization to 32P-labeled plasmid. The other (RNA dot hybridization) used covalent attachment of RNA to activated cellulose paper squares and hybridization to 32P-labeled plasmid. As probe, we used a hybrid plasmid (pBR322-GH1) which we show by restriction analysis to contain a DNA sequence coding for rat GH. The results were comparable from both techniques and showed that incubation of GH3 cells with a thyroid hormone (triiodothyronine), a glucocorticoid hormone (dexamethasone), or both hormones caused an increase of cytoplasmic pre-GH mRNA sequences of about 4-, 22-, and 13-fold, respectively. Results obtained with the RNA gel blot hybridization method showed that hormonal stimulation leads to the induction of a single 1.0-kilobase species of pre-GH mRNA in the cytoplasm and of 2.7- and 1.0- kilobase species of GH-specific RNA in the nucleus.

Animals↗