Are dendritic cells the key to liver transplant tolerance?
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Animals↗
Biomedical subjects
L Lu
Publications and source records attributed to L Lu.
Elimination of nonspecific radioactivity from [76Br]bromide in PET study with [76Br]bromodeoxyuridine.
[76Br]Bromodeoxyuridine ([76Br]BrdU) might allow a determination of proliferation in vivo using positron emission tomography (PET), but only with consideration of organ nonspecific radioactivity constituted by [76Br]bromide. A first study assessed the potential of diuretics to eliminate [76Br]bromide. [76Br]Bromide was injected in the vein of rats and different diuretic combinations were given. Urine was collected and radioactivity measured. Torasemide plus sodium chloride gave better 76Br elimination than the other diuretics. In a second experiment, rats were given [76Br]BrdU. After the radioactivity injection, the rats of the treatment group were given torasemide plus NaCl. At 44 h after the radioactivity injection, the radioactivity concentration and the fraction incorporated into DNA were measured in different organs. Using diuretics, the elimination of [76Br]bromide was increased. The radioactivity decreased 30-50% in most of the organs but the highest radioactivity uptake was found in the organs with more active DNA synthesis. This method may facilitate the use of [76Br]BrdU as a tracer for DNA synthesis using PET.
Animals↗
Adenoviral delivery of CTLA4Ig into myeloid dendritic cells promotes their in vitro tolerogenicity and survival in allogeneic recipients.
Dendritic cells (DC) are highly specialized antigen-presenting cells (APC) that initiate and modulate immune responses. They are essential for naive T cell activation, but may also play roles both in central and peripheral tolerance. Blockade of costimulatory pathways that provide the crucial second signal for lymphocyte activation is one strategy to augment the potential tolerogenicity of DC. Here, in vitro propagated DC were transduced using an adenoviral (Ad) vector to express the gene encoding cytotoxic T lymphocyte antigen 4-immunoglobulin (CTLA4lg), which blocks interaction of CD80 and CD86 on DC with CD28 on T cells. Supernatants of AdCTLA4lg-transduced DC strikingly inhibited mixed leukocyte reactions (MLR) induced by non-transduced DC. Whereas transduction of marker genes (LacZ or enhanced green fluorescence protein (EGFP)) did not alter their potent allostimulatory activity, DC transduced with CTLA4lg exhibited striking reductions in cell surface staining for CD86, but not MHC class II, and were poor stimulators of T cell proliferation and cytotoxic T lymphocyte (CTL) responses. In addition, they induced alloantigen-specific T cell hyporesponsiveness. They were detected, following local injection, in significantly increased numbers in the lymphoid tissue of unmodified allogeneic recipients. This is the first report of the functional properties of DC genetically engineered to express CTLA4lg.
Abatacept↗
Synthesis and characterization of binding of 5-[76Br]bromo-3-[[2(S)-azetidinyl]methoxy]pyridine, a novel nicotinic acetylcholine receptor ligand, in rat brain.
5-[76Br]Bromo-3-[[2(S)-azetidinyl]methoxy]pyridine ([76Br]BAP), a novel nicotinic acetylcholine receptor ligand, was synthesized using [76Br]bromide in an oxidative bromodestannylation of the corresponding trimethylstannyl compound. The radiochemical yield was 25%, and the specific radioactivity was on the order of 1 Ci/micromol. The binding properties of [76Br]BAP were characterized in vitro and in vivo in rat brain, and positron emission tomography (PET) experiments were performed in two rhesus monkeys. In association experiments on membranes of the cortex and thalamus, >90% of maximal specific [76Br]BAP binding was obtained after 60 min. The dissociation half-life of [76Br]BAP was 51 +/- 6 min in cortical membranes and 56 +/- 3 min in thalamic membranes. Saturation experiments with [76Br]BAP revealed one population of binding sites with dissociation constant (K(D)) values of 36 +/- 9 and 30 +/- 9 pM in membranes of cortex and thalamus, respectively. The maximal binding site density (Bmax) values were 90 +/- 17 and 207 +/- 33 fmol/mg in membranes of cortex and thalamus, respectively. Scatchard plots were nonlinear, and the Hill coefficients were <1, suggesting the presence of a lower-affinity binding site. In vitro autoradiography studies showed that binding of [76Br]BAP was high in the thalamus and presubiculum, moderate in the cortex and striatum, and low in the cerebellum and hippocampus. A similar pattern of [76Br]BAP accumulation was observed by ex vivo autoradiography. In vivo, binding of [76Br]BAP in whole rat brain was blocked by preinjection of (S)(-)-nicotine (0.3 mg/kg) by 27, 52, 68, and 91% at survival times of 10, 25, 40, 120, and 300 min, respectively. In a preliminary PET study in rhesus monkeys, the highest [76Br]BAP uptake was found in the thalamus, and radioactivity was displaceable by approximately 60% with cytisine and by 50% with (S)(-)-nicotine. The data of this study indicate that [76Br]BAP is a promising radioligand for the characterization of nicotinic acetylcholine receptors in vivo.
Alkaloids↗
Personal or environmental causes of happiness: a longitudinal analysis.
The author analyzed an integrative model of happiness, which incorporated personal factors (demographics, extraversion, neuroticism, and locus of control) and environmental factors (life events and social support), using a longitudinal data set. A secondary purpose was to clarify the relationship between overall happiness and life satisfaction. Using systematic random sampling, 581 residents of Kaohsiung, Taiwan, completed structured questionnaires at Time 1; among them, 105 returned valid questionnaires 2.5 years later, at Time 2. Longitudinal analysis indicated moderate stability of the subjective well-being (SWB) measures. More importantly, when both the baseline SWB levels and personality traits were statistically controlled, social support still predicted overall happiness, and positive life events predicted life satisfaction. Furthermore, there was a consistently strong bidirectional relationship between overall happiness and life satisfaction.
Adolescent↗
Detection of body movements during sleep by monitoring of bed temperature.
We have modified a previously developed bed temperature monitor and used it to evaluate a sleeper's body movements. Sleep was monitored both at home and in the laboratory in normal subjects. From laboratory monitoring, a new algorithm to assess body movements using the sum of a square of temperature differences (SSD(t)) method was proposed, and the best conditions for detection of body movements are discussed. The experiment was performed with 12 normal male subjects and the body movement obtained from temperature changes was compared with that from video images. The sensitivity and positive predictive accuracy of body movement at the lower limbs with a sampling interval of 15 s and a threshold value of 0.2 degrees C2 were 88.7% and 95.4% respectively, over a total of 22 nights' observation. The results show that body movement can be accurately detected by placing one belt sensor under the lower limbs with a sampling interval of 15 s and a threshold value of 0.2 degrees C2 in SSD(t) analysis. We also found that body movement frequency is different among individuals during sleep, but has a certain range for an individual. No significant relationship between average body movement or average time in bed (TIB) and sleep profiles was observed among individuals for all subjects in one week of home monitoring. However, significant relationships between frequency of body movement or TIB and sleep profiles were observed in the long-term home monitoring for an individual. This suggests that body movements and TIB detected by bed temperature measurement can be used as indices for the assessment of sleep stability and continuity.
Adult↗
Functional role of ionic regulation of Na+/Ca2+ exchange assessed in transgenic mouse hearts.
Na+/Ca2+ exchange is the primary mechanism mediating Ca2+ efflux from cardiac myocytes during diastole and, thus, can prominently influence contractile force. In addition to transporting Na+ and Ca2+, the exchanger is also regulated by these ions. Although structure-function studies have identified protein regions of the exchanger subserving these regulatory processes, their physiological importance is unknown. In this study, we examined the electrophysiological and mechanical consequences of cardiospecific overexpression of the canine cardiac exchanger NCX1.1 and a deletion mutant of NCX1.1 (Delta680-685), devoid of intracellular Na+ (Na+i)- and Ca2+ (Ca2+i)- dependent regulatory properties, in transgenic mice. Using the giant excised patch-clamp technique, normal ionic regulation was observed in membrane patches from cardiomyocytes isolated from control and transgenic mice overexpressing NCX1.1. In contrast, ionic regulation was nearly abolished in mice overexpressing Delta680-685, indicating that the native regulatory processes could be overwhelmed by expression of the transgene. To address the physiological consequences of ionic regulation of the Na+/Ca2+ exchanger, we examined postrest force development in papillary muscles from NCX1.1 and Delta680-685 transgenic mice. Postrest potentiation was found to be substantially greater in Delta680-685 than in NCX1.1 transgenic mice, supporting the notion that ionic regulation of Na+/Ca2+ exchange plays a significant functional role in cardiac contractile properties.
Animals↗
Genetic and epigenetic susceptibility to endogenous retrovirus-induced lymphomas in SL mice.
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Animals↗
Genetic determination of cardiac mass in normotensive rats: results from an F344xWKY cross.
Genetic determinants affect adult cardiac mass and the predisposition to develop cardiac hypertrophy. The aim of this study was to identify quantitative trait loci (QTL) that control heart and left ventricular (LV) weight by use of normotensive inbred rat strains that differ in their adult cardiac mass phenotype. We studied 126 male F2 rats derived from a cross of normotensive Wistar-Kyoto and Fischer 344 rats. At 12 weeks of age, total heart weight and LV weight were measured. Genomic DNA from these animals was screened by use of polymorphic microsatellite markers across the whole genome (excluding the sex chromosomes). In this cross, the genetic contribution to total heart weight variation was 56%, and the genetic contribution for LV weight was 55%. Using the Mapmaker/QTL computer package, we identified a significant QTL on chromosome 3 with a log10 likelihood (LOD) score of 4.8, which accounted for 16.5% of the total variance of LV weight. This QTL was centered close to the marker D3Rat29. The QTL was also found to be significantly linked with total heart weight (LOD=4.4). These data provide the first demonstration of a QTL on chromosome 3 that plays a role in determining the difference in LV mass between normotensive Fischer 344 and Wistar- Kyoto inbred rat strains. The prostaglandin synthase 1 gene is located within the QTL.
Animals↗
Major peptide autoepitopes for nucleosome-specific T cells of human lupus.
We tested 154 peptides spanning the entire length of core histones of nucleosomes for the ability to stimulate an anti-DNA autoantibody-inducing T helper (Th) clone, as well as CD4(+) T-cell lines and T cells, in fresh PBMCs from 23 patients with lupus erythematosus. In contrast to normal T cells, lupus T cells responded strongly to certain histone peptides, irrespective of the patient's disease status. Nucleosomal peptides in histone regions H2B(10-33), H4(16-39) (and overlapping H4(14-28)), H4(71-94), and H3(91-105) (and overlapping H3(100-114)) were recurrently recognized by CD4 T cells from the patients with lupus. Remarkably, these same peptides overlap with major epitopes for the Th cells that induce anti-DNA autoantibodies and nephritis in lupus-prone mice. We localized 2 other recurrent epitopes for human lupus T cells in H2A(34-48) and H4(49-63). All the T-cell autoepitopes have multiple HLA-DR binding motifs, and the epitopes are located in histone regions recognized by lupus autoantibodies, suggesting a basis for their immunodominance. Native nucleosomes and their peptides H4(16-39), H4(71-94), and H3(91-105) induced a stronger IFN-gamma response, whereas others, particularly, H2A(34-48), favored an IL-10- and/or IL-4-positive T-cell response. The major autoepitopes may reveal the mechanism of autoimmune T-cell expansion and lead to antigen-specific therapy of human lupus.
Adolescent↗
Passive smoking and nonrecurrent acute otitis media in children.
INTRODUCTION: It remains uncertain whether passive smoking is a risk factor (RF) for nonrecurrent acute otitis media (AOM). The aim of this study was to evaluate whether exposure to second-hand smoke at home increased the prevalence of an isolated single episode of nonrecurrent AOM in children. METHODS AND MATERIAL: We performed a cross-sectional study with 192 children younger than 3 years who were seen at a general pediatric clinic. A questionnaire was used to quantify the exposure to cigarette smoke at home and to assess other RFs for AOM. The diagnosis of AOM was made by pediatricians using otoscopy. The results of the associations were reported by prevalence ratios with 95% confidence intervals. Multiple logistic regression was used to investigate the role of confounding variables among other potential RFs and passive smoking. RESULTS: The prevalence ratio of an isolated single episode of nonrecurrent AOM between patients exposed and those not exposed to passive smoking was 0.82 (0.67 to 1.02). In logistic regression, any RF changed the main association significantly. CONCLUSION: Exposure to passive smoking did not change the prevalence of an isolated single episode of nonrecurrent AOM in children.
Acute Disease↗
[Analysis of fibronectin and laminin in the extracellular matrixes of acute myeloid leukemia and its implications].
OBJECTIVE: To investigate the relationship between quantitative change of fibronectin (Fn) or Laminin (Lm) and growth and differentiation of leukemic cells. METHODS: The extracellular matrixes, Fn and Lm, in long-term bone marrow culture (LTBMC) from 18 acute myeloid leukemia (AML) patients and 6 normal subjects were examined by immunofluorescence assay. RESULTS: 1. The Fn or Lm content in 9 AML self-maintained (AMLsm) 1-3 week-cultures was significantly less than that in 9 AML not self-maintained (AMLnsm) cultures. 2. In the third week's cultures, the blasts of 8 AMLnsms decreased to less than 5%, but did not of 7 AMLsms. 3. As the cultures going on, the blasts were related to Fn or Lm contents positively in normal control and negatively in AMLnsm. The blasts were related to Fn contents negatively in AMLsm. CONCLUSION: The change of Fn or Lm may play an important role in the development of AML. In addition, the difference of Fn or Lm contents between AMLsm and AMLnsm was helpful to the choice of AML patient for in vitro purging of leukemic cells through LTBMC before auto-BMT.
Adolescent↗
[The relationship between tissue tumor necrosis factor-alpha(TNF-alpha) mRNA expression and gut-derived endotoxemia in rats after thermal injury].
OBJECTIVE: To investigate the dynamic changes in tumor necrosis factor-alpha(TNF-alpha) mRNA expression and the relationship between TNF-alpha mRNA and gut-derived endotoxemia in rats after thermal injury. METHODS: 56 male Wistar rats were subjected to a 35% total body surface area full-thickness thermal injury and randomly divided into 3 groups: normal controls, 35% III* injury group, and polymyxin B treatment group. Plasma endotoxin was measured by limulus amebocyte lysate test, and tissue TNF-alpha mRNA expression was determined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: It was found that a significant elevation of endotoxin concentration in both portal and systemic circulation was observed at 2 hours after thermal injury, peaking at 8 hours (P < 0.05-0.01) and lowering at 24 hours. Meanwhile, TNF-alpha mRNA expression significantly increased in liver, lung, intestine, and kidney at 2 hours, peaking at 8 hours, and a high level was maintained till 24 hours. However, treatment with a low-dose polymyxin B could lower both portal and systemic endotoxin levels, and markedly inhibit TNF-alpha mRNA expression in various organs. In addition, a positive correlation between portal endotoxin concentration and pulmonary, intestinal and renal TNF-alpha mRNA expression was noted (r = 0.365-0.484, all P < 0.05). CONCLUSION: This study suggests that major burns can lead to a marked elevation of tissue TNF-alpha mRNA expression in vital organs, which may be associated with gut-derived endotoxemia caused by acute thermal injury.
Animals↗
Effects of Kupffer cells stimulated by triglyceride and very low-density lipoprotein on proliferation of rat hepatic stellate cells.
OBJECTIVE: To study the effects of triglyceride, very low-density lipoprotein (VLDL), and Kupffer cell-conditioned medium (KCCM) derived from triglyceride and VLDL treatment on proliferation of rat hepatic stellate cells (HSC). METHODS: HSC and Kupffer cells were isolated and cultured from liver of Wistar rats by in situ perfusion with proteinase and collagenase, and density gradient centrifugation with Nycodenz; HSC and Kupffer cells were identified by immunohistochemistry, endocytosis, and ultrastructure, etc. Kupffer cells were incubated with triglyceride (25 micrograms/ml) and VLDL (25 micrograms/ml) for 24 hours, KCCM were prepared, and MTT colorimetric assay was detected for HSC proliferation. RESULTS: HSC proliferation was 0.1894 +/- 0.0316 (12.5 micrograms/ml), 0.1637 +/- 0.0243 (25 micrograms/ml), 0.1450 +/- 0.0264 (50 micrograms/ml), 0.1212 +/- 0.0275 (100 micrograms/ml), 0.1226 +/- 0.0138 (200 micrograms/ml) and 0.0990 +/- 0.0163 (400 micrograms/ml) in the presence of triglyceride and was 0.1583 +/- 0.0314 (6.25 micrograms/ml), 0.1642 +/- 0.0269 (12.5 micrograms/ml), 0.1834 +/- 0.0498 (25 micrograms/ml), 0.1964 +/- 0.0287 (50 micrograms/ml) and 0.2202 +/- 0.0284 (100 micrograms/ml) in presence of VLDL, respectively. Compared with the control, HSC proliferation at 400 micrograms/ml of triglyceride was lower (P < 0.01), but at 12.5 micrograms/ml of triglyceride and 25, 50, 100 micrograms/ml of VLDL higher (P < 0.05 or 0.01); HSC proliferation was 0.1569 +/- 0.0144, 0.1924 +/- 0.0113 and 0.1871 +/- 0.0116 in the presence of KCCM, KCCM + triglyceride and KCCM + VLDL, respectively. Compared with the control and KCCM, KCCM + triglyceride and KCCM + VLDL might promote HSC proliferation (P < 0.01); there was no statistical significance between KCCM + triglyceride and KCCM + VLDL (P > 0.05); KCCM was greater in HSC proliferation than the control, but there was no significant change (P > 0.05). CONCLUSIONS: Triglyceride, VLDL, and KCCM stimulated by triglyceride and VLDL might promote HSC proliferation and be associated with fatty liver and hepatic fibrogenesis.
Animals↗
[Clinical and experimental study of 9 cases of adult T cell leukemia].
OBJECTIVE: In order to clarify the clinical and laboratory features of adult T cell leukemia (ATL): morphology, immunology, cytogenetics, serology and molecular biology. METHODS: Indirect immunofluorescence assay and ELISA were used to detect serum HTLV-I antibody. The HTLV-I provirus sequence were amplified by PCR and confirmed by liquid hybridization. RESULTS AND CONCLUSION: Nine cases of ATL were diagnosed. The major clinical manifestation was lymph node enlargement found in all patients. Skin involvement and osteolysis were not frequent. The characteristic finding was leukemic cells with highly indented or lobulated flower-like nuclei in peripheral blood and bone marrow. ATL cells were CD2, CD3, CD4, CD25 positive and CD8 negative. No specific chromosome abnormality or HLA type was found. Seven of 8 patients examined had HTLV-I antibody. The HTLV-I provirus genome sequence integrated into host cell DNA was amplified by PCR and confirmed by liquid hybridization. All of these results showed that HTLV-I was also the etiological agent of ATL in China. One of the 9 cases of ATL was classified as lymphoma type, one as chronic-type, and the rest as acute type.
Adult↗
[Intercellular adhesion molecule-1 expression in experimental liver fibrosis].
OBJECTIVE: To explore the role of intercellular adhesion molecule-1 (ICAM-1) in experimental liver fibrosis. METHODS: Experimental liver fibrosis models of rats were induced by high fat diet, low fat diet plus ethanol, high fat diet plus ethanol, and carbon tetrachloride subcutaneous injection respectively. At sacrifice, liver pathologic changes were studied and ICAM-1 expression was evaluated with immunohistochemistry by using a monoclonal antibody. RESULTS: ICAM-1 expression was observed in the hepatocellular membrane; ICAM-1 positive hepatocytes were localized in zones of portal tract with focal necrosis and inflammatory damage. Staining for ICAM-1 was associated with the degree of liver inflammation and fibrosis. In the different models, the intensity of ICAM-1 expression was different; It ranged in an increasing order from high fat diet, low fat diet plus ethanol, high fat diet plus ethanol, and carbon tetrachloride model. The strongest reactivity for ICAM-1 was seen in carbon tetrachloride model (P < 0.05), the difference was significant as compared with the other models. However, there was no significant difference among the three other models (P > 0.05). CONCLUSION: Upregulation of ICAM-1 expression in experimental liver fibrosis may be related with liver fibrogenesis.
Animals↗
[Effects of Kupffer cells stimulated by triglyceride and very low-density lipoprotein on proliferation of rat hepatic stellate cells].
OBJECTIVE: To study the effects of Kupffer cell-conditioned medium (KCCM) derived from triglyceride and very low-density lipoprotein (VLDL) treatment on proliferation of rat hepatic stellate cells (HSC). METHODS: HSC and Kupffer cells were isolated from liver of Wistar rats by in situ perfusion with pronase and collagenase and density gradient centrifugation with Nycodenz and then cultured. KCCM was prepared and MTT colorimetric assay was used to detect HSC proliferation. RESULTS: HSC and Kupffer cells were isolated successfully with high purity. 12.5 mg/L of triglyceride and 25 - 100 mg/L of VLDL promoted HSC proliferation (P < 0.05 or 0.01); KCCM + triglyceride and KCCM + VLDL might promote HSC proliferation as compared with a control group (P < 0.01). There was no significant difference between KCCM + triglyceride and KCCM + VLDL (P > 0.05). CONCLUSION: The technique for isolation of HSC and Kupffer cells described here is simple and reliable. Triglyceride, VLDL and KCCM stimulated by them may promote HSC proliferation and be associated with fatty liver and hepatic fibrogenesis.
Animals↗
[A study on tumor necrosis factor alpha, macrophage inflammatory protein-2 and myeloperoxidase in blood, broncho-alveolar fluid and lung tissues of rat chronic bronchitis model].
OBJECTIVE: To study the nature and mechanisms of airway inflammation in chronic bronchitis and observe the effects of inhaled glucocorticoids on inflammatory indices. METHODS: Rat chronic bronchitis model was established by intratracheal instillation of small dose of lipopolysaccharide (LPS, 1 g/L). Experiments were performed in 28 male Sprague-Dawley rats, which comprised four groups in random, i.e. chronic bronchitis model group, normal saline treated group, dexamethasone treated group and healthy control group. The levels of myeloperoxidase (MPO) of blood and lung tissues, and tumor necrosis factor (TNF)alpha and macrophage inflammatory protein-2 (MIP-2) of plasma, broncho-alveolar fluid (BALF) and lung tissues were determined by biochemical and ELISA methods. Total and differential white blood cell counts of BALFwere carried out. RESULTS: (1) The levels of TNFalpha and MIP-2 in BALF and lung tissues, and MPO in lung tissues of chronic bronchitis model group were significantly increased than those of control group (P < 0.05). (2) More significant increase in total white blood cell count and neutrophils in BALF was found in rat chronic bronchitis group than in control group (P < 0.001). (3) Significant positive correlations were observed between the level of MPO and MIP-2 of lung tissues, the level of MPO and TNFalpha of lung tissue and the total cell counts and the level of MIP-2 of BALF and lung tissue. (4) More significant decrease in total cell counts and neutrophils of BALF and levels of MPO in lung tissue was found in dexamethasone-treated group as compared to those of chronic bronchitis group. CONCLUSION: Recruitment and activation of neutrophils seem to be the characteristics of chronic bronchitis. TNFalpha and MIP-2 may be involved in the process of chemotaxis and activation in airway inflammation in chronic bronchitis. Inhaled steroids might have some effects on chronic bronchitis by limiting the airway inflammation.
Animals↗