PubMed Health⌕ Search

Biomedical subjects

Jun Lu

Publications and source records attributed to Jun Lu.

At least 127 records · Page 7Linked to original sources
PubMed2004

Metabolism of thalidomide in liver microsomes of mice, rabbits, and humans.

Thalidomide is increasingly important in clinical treatment, not only of various inflammatory conditions but also in multiple myeloma and other malignancies. Moreover, the metabolism of thalidomide varies considerably among different species, indicating a need to understand its mechanistic basis. Our previous in vivo studies showed the plasma half-life of thalidomide to be much shorter in mice than in humans, with rabbits showing intermediate values. We were unable to detect hydroxylated thalidomide metabolites in humans and suggested that interspecies differences in thalidomide hydroxylation might account for the differences in plasma half-life. We sought here to establish whether these species differences in the formation of hydroxylated thalidomide metabolites could be discerned from in vitro studies. Liver microsomes of mice, rabbit, and human donors were incubated with thalidomide and analyzed using liquid chromatography-mass spectrometry. Hydrolysis products were detected for all three species, and the rates of formation were similar to those for spontaneous hydrolysis, except in rabbits where phthaloylisoglutamine formation increased linearly with microsomal enzyme concentration. Multiple hydroxylation products were detected, including three dihydroxylated metabolites not observed in vivo. Thalidomide-5-O-glucuronide, detected in vivo, was absent in vitro. The amount of 5-hydroxythalidomide formed was high in mice, lower in rabbits, and barely detectable in humans. We conclude that major interspecies differences in hepatic metabolism of thalidomide relate closely to the rate of in vivo metabolite formation. The very low rate of in vitro and in vivo hydroxylation in humans strongly suggests that thalidomide hydroxylation is not a requirement for clinical anticancer activity.

Animals↗
PubMed2004

Multiepitope Trojan antigen peptide vaccines for the induction of antitumor CTL and Th immune responses.

We describe in this study a strategy to produce synthetic vaccines based on a single polypeptide capable of eliciting strong immune responses to a combination CTL and Th epitopes with the purpose of treating malignancies or preventing infectious diseases. This strategy is based on the capacity of Trojan Ags to deliver exogenous Ags into the intracellular compartments, where processing into MHC-binding peptides takes place. Our previous work demonstrated that Trojan Ags containing a CTL epitope localized to intracellular compartments, where MHC class I-binding peptides were generated in a TAP-independent fashion by the action of various exopeptidases and the endopeptidase furin. In this study, we report that Trojan Ags containing several CTL epitopes joined via furin-sensitive linkers generated all of the corresponding MHC class I-binding peptides, which were recognized by CTL. However, Trojan Ags prepared with furin-resistant linkers failed to produce the MHC class I-binding peptides. We also present data indicating that Trojan Ags bearing both CTL and Th epitopes can generate the corresponding MHC class I- and II-binding peptides, which are capable of stimulating T cell responses. Most significantly, in vivo vaccination of mice with a single injection of multiepitope Trojan Ags resulted in strong CTL and Th responses that translated into significant antitumor responses in a model of malignant melanoma. The overall results indicate that Trojan Ags prepared with furin-sensitive linkers are ideal candidates for producing synthetic multiepitope vaccines for the induction of CTL and Th responses that could be used against a variety of diseases, including cancer.

Animals↗
PubMed2004

Analysis of T-cell repertoire in hepatitis-associated aplastic anemia.

Hepatitis-associated aplastic anemia (HAA) is a syndrome of bone marrow failure following an acute attack of seronegative hepatitis. Clinical features and liver histology suggest a central role for an immune-mediated mechanism. To characterize the immune response, we investigated the T-cell repertoire (T-cell receptor [TCR] V(beta) chain subfamily) of intrahepatic lymphocytes in HAA patients by TCR spectratyping. In 6 of 7 HAA liver samples, a broad skewing pattern in the 21 V(beta) subfamilies tested was observed. In total, 62% +/- 18% of HAA spectratypes showed a skewed pattern, similar to 68% +/- 18% skewed spectratype patterns in 3 of 4 patients with confirmed viral hepatitis. Additionally, the T-cell repertoire had similarly low levels of complexity. In the peripheral blood lymphocytes (PBLs) of a separate group of HAA patients prior to treatment, 60% +/- 15% skewed spectratypes were detected, compared with only 18% +/- 8% skewed spectratypes in healthy controls. After successful immunosuppressive treatment, an apparent reversion to a normal T-cell repertoire with a corresponding significant increase in T-cell repertoire complexity was observed in the HAA samples. In conclusion, our data suggest an antigen-driven T-cell expansion in HAA and achievement of a normal T-cell repertoire during recovery from HAA.

Anemia, Aplastic↗
PubMed2004

Characterization of surface property of poly(lactide-co-glycolide) after oxygen plasma treatment.

In this study, poly (lactide-co-glycolide) (PLGA) films were treated by oxygen plasma. The surface structure, topography and surface chemistry of treated PLGA films were characterized by contact angle measurement, scanning electron microscope observation, atomic force microscopy, and X-ray photoelectron spectrum analysis. The cell affinity of the oxygen plasma treated films was evaluated under dynamic conditions by Parallel Plate Flow Chamber (PPFC). The results showed that the hydrophilicity increased greatly after oxygen plasma treatment. High quantities of -C-O groups, such as hydroxyl and peroxyl groups could be incorporated into the surface of PLGA (70/30) by controlling appropriate plasma treatment conditions. Moreover, the oxygen plasma treatment resulted in formation of peaks and valleys on the sample surfaces, and the roughness increased with treatment time. Cells stretched very well and the ability to endure the shear stress was improved greatly after the PLGA (70/30) was modified by appropriate plasma treatment, i.e. under 50W for 2 or 10 min. However, when the treatment time was increased to 20 min, the percentage of adherent cells on the roughest surface decreased because the content of polar groups incorporated onto the surface decreased. The results showed that improved cell adhesion was attributed to the combination of surface chemistry and surface morphology of PLGA during plasma etching.

Animals↗
PubMed2004

Continuous methane fermentation and the production of vitamin B12 in a fixed-bed reactor packed with loofah.

A fixed-bed reactor with acclimated methanogens immobilized on a loofah support was studied on a laboratory scale to evaluate the system producing methane from the mixture of CO(2) and H(2) gas, with the production of vitamin B(12) as a by-product. Fermentation using CO(2)/H(2) acclimated methanogens was conducted in a jar fermentor with hydraulic retention times (HRTs) of three and six days. The performance of the reactor was mainly dependent on the HRT. With an HRT of three days, the methane production rate and the vitamin B(12) concentration in the culture broth were 6.18 l/l-reactor/h and 2.88 mg/l-culture liquid; these values were 11.96 l/l-reactor/h and 37.54 mg/l-culture liquid for an HRT of six days. A higher total cell mass of methanogens retained 42.5 g dry cell/l-culture liquid was achieved in the HRT of six days. The loofah carrier immobilized almost 95% of the methanogens, which led to a more effective bio-reaction. It was also observed that the fermentation system had a better ability to buffer pH, especially for an HRT of six days.

Bioreactors↗
PubMed2004

Lipopolysaccharide suppresses albumin expression by activating NF-kappaB in rat hepatocytes.

BACKGROUND: The severity of hypoalbuminemia has been shown to be related to morbidity and mortality in critical illness, illustrating the need for better understanding of the molecular mechanism of hypoalbuminemia. Lipopolysaccharide(LPS) is a key mediator which induces hypoalbuminemia in sepsis and septic shock. The present studies were performed to identify whether the reduction of albumin expression induced by LPS was mediated by activating nuclear factor kappa B(NF-kappaB) in cultured rat hepatocytes. MATERIALS AND METHODS: Primary rat hepatocytes were divided into five groups treated with normal saline or 1 ng/ml, 0.01 microg/ml, 0.1 microg/ml, or 1 microg/ml of LPS for 24 h. The albumin level in the supernatant and NF-kappaB activity in hepatocytes were measured. Hepatocytes were pretreated for 30 min with SN50 (a highly selected inhibitor of NF-kappaB) at different concentrations (10, 30, and 50 microg/ml). After 24 h of treatment with 1 microg/ml of LPS, the culture medium was measured for albumin level. Meanwhile, NF-kappaB activity in hepatocytes was assayed. RESULTS: LPS dramatically decreased albumin expression and enhanced NF-kappaB activity in rat hepatocytes, especially in the 1 microg/ml LPS group. This reduction in albumin expression induced by LPS can be completely inhibited by SN50 in different concentrations, and the maximal increase in albumin was observed at a SN50 dosage of 30 microg/ml. CONCLUSIONS: The results suggest that LPS inhibits albumin expression by activating NF-kappaB signaling. NF-kappaB is a critical signaling pathway in LPS-induced hypoalbuminemia which it is worthwhile to understand in studying the molecular mechanism of hypoalbuminemia in sepsis and septic shock.

Albumins↗
PubMed2004

Specific inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates vascular proliferation in monocrotaline-induced pulmonary hypertension in rats.

OBJECTIVES: p38 mitogen-activated protein kinase is associated with many clinical entities characterized by inflammation. We postulated that inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates inflammation and the development of pulmonary hypertension in monocrotaline-treated rats. METHODS: Rats were divided into 4 groups: (1) the control group (daily 0.9% saline), (2) the FR group (daily FR167653, 2 mg . kg(-1) . d(-1)), (3) the MCT group (daily 0.9% saline the day after a single monocrotaline dose, 60 mg/kg), and (4) the MCT+FR group (daily FR167653, 2 mg . kg(-1) . d(-1), the day after a single MCT dose). Body weight, pulmonary artery pressure, and morphometric changes of the pulmonary artery with the histopathologic method were observed weekly for 4 weeks. Also, p38 mitogen-activated protein kinase activity and inflammatory cytokine expression in the lung were measured. RESULTS: Four weeks after monocrotaline administration, mean pulmonary artery pressure in the MCT+FR group was lower than in the MCT group (MCT+FR vs MCT: 24.7 +/- 1.9 vs 36.5 +/- 2.1 mm Hg; P < .05). In morphometric analysis the percentage of medial wall thickness and the percentage of muscularization in the MCT+FR group were reduced compared with those in the MCT group after 4 weeks (P < .05); however, the number of macrophages was not significantly different. p38 mitogen-activated protein kinase activity was significantly attenuated in the MCT+FR group compared with in the MCT group (7.2 +/- 0.52 vs 2.1 +/- 0.23 fold-increase, P < .05, at 1 week). Although mRNA levels of tumor necrosis factor alpha and interleukin 1beta were reduced in the MCT+FR group compared with in the MCT group (tumor necrosis factor alpha: 1.18 +/- 0.36 vs 3.05 +/- 1.12 fold-increase, P < .05, at 2 weeks; interleukin 1beta: 2.2 +/- 0.34 vs 4.4 +/- 1.09 fold-increase, P < .05, at 1 week), FR167653 did not suppress increased monocyte chemotactic protein 1 mRNA expression induced by monocrotaline (3.2 +/- 0.62 vs 3.1 +/- 0.42 fold-increase, at 1 week). CONCLUSION: FR167653 significantly attenuates the expression of inflammatory cytokines, ultimately preventing the progression of pulmonary hypertension. These results suggest that p38 mitogen-activated protein kinase might play a central role in the molecular events that underlie the development and progression of pulmonary hypertension.

Animals↗
PubMed2004

Histone acetyltransferase activity of p300 enhances the activation of IL-12 p40 promoter.

Interleukin-12 (IL-12) is a heterodimeric cytokine produced by macrophages in response to intracellular pathogens and provides an obligatory signal for the differentiation of T-helper-1 cells. p300 is an important histone acetyltransferase (HAT) and has been implicated in the regulation of gene expression. Whether p300 plays a role in the IL-12 expression has not been investigated before. In this study, we analyzed the roles of p300 in the regulation of human IL-12 p40. By using RT-PCR and a series of co-transfection studies, we found that p300 had a stimulating effect on the expression of endogenous IL-12 p40 mRNA and on the activity of IL-12 p40 promoter. We also showed that the HAT activity of p300 was essential to its function in regulating IL-12 promoter, since the mutant p300 with the HAT domain deleted did not have such a stimulation effect. In addition, the adenovirus E1A protein suppressed the p300 function, whereas the mutant E1A lacking the p300 interaction domain did not. Furthermore, p300 was able to reinforce the c-Rel-mediated activation of IL-12 p40. Results presented in this paper implicate that p300 is involved in the transcriptional regulation of IL-12 p40, and IL-12 p40 is one of the target genes of p300.

Acetyltransferases↗
PubMed2004

A comparison of gene expression profiles produced by SAGE, long SAGE, and oligonucleotide chips.

A comparison study of short SAGE versus GeneChip and long SAGE was conducted to determine if data were interchangeable between the techniques. Although SAGE and Affymetrix chip expression levels showed a significant correlation using the set of genes for which there was reliable and unambiguous mapping from tag-to-gene identification, correlation coefficients were low (0.51 for the Spearman's correlation coefficient with p < 0.0001). A quantitative analysis comparing the use of 10-bp SAGE tags to 17-bp SAGE tags indicated that the short SAGE technology was more efficient at identifying differentially expressed tags. However, 4-7% of the 10-bp tags were redundancies that could have been resolved by long SAGE and 10-20% of the short SAGE tags had no obvious match to currently annotated human transcript sequences.

DNA, Complementary↗
PubMed2004

Trichostatin A extends the lifespan of Drosophila melanogaster by elevating hsp22 expression.

The level of acetylation of histones in nucleosomes is related to the longevity of yeast and animals. However, the mechanisms by which acetylation and deacetylation affect longevity remain unclear. In present study, we investigated the influence of histone acetylation modification on the expression of hsp22 gene and the lifespan in Drosophila melanogaster using histone deacetylase (HDAC) inhibitor Trichostatin A (TSA). The results showed that TSA could extend the lifespan of Drosophila melanogaster. Furthermore, TSA significantly promoted the hsp22 gene transcription, and affected the chromatin morphology at the locus of hsp22 gene along the polytene chromosome. Present data implicate that TSA may affect the lifespan of Drosophila through changing the level of histone acetylation and influencing the expression of hsp22 gene that is related to aging.

Acetylation↗
PubMed2004

The role of H-NS in silencing F transfer gene expression during entry into stationary phase.

The conjugative ability of the F plasmid of Escherichia coli is highly growth phase dependent, with plasmid transfer efficiency dropping rapidly as donor cells progress through the growth cycle towards stationary phase. Transfer is dependent on the expression of the plasmid transfer (tra) genes, which are controlled by three plasmid-encoded regulatory proteins: TraJ, TraY and TraM. Here, we show that the nucleoid-associated host protein, H-NS, acts to repress the expression of traM and traJ as cells enter stationary phase, thereby decreasing mating ability to barely detectable levels. Sequence analysis identified regions of predicted intrinsic curvature, to which H-NS preferentially binds, at the promoters of both traM and traJ. H-NS binding at these regions was then confirmed by electrophoretic mobility shift and DNase I protection footprinting assays. Immunoblot assays displayed a significant increase in TraJ and TraM levels in an hns mutant strain. These findings were further supported by Northern and primer extension analyses which showed that whereas both genes were only expressed in early exponential phase in wild-type cells, hns mutant cells exhibited drastic derepression throughout the growth cycle. Transcriptional fusion studies of the individual promoters demonstrated that H-NS-mediated repression was observed when the promoters of both traM and traJ were present in cis to each other. This suggests that H-NS may bind to an extended region of the F plasmid, acting as a regional silencer of promoters for traJ and traM.

Bacterial Outer Membrane Proteins↗
PubMed2004

Properties of ets-1 binding to chromatin and its effect on platelet factor 4 gene expression.

Ets-1 is important for transcriptional regulation in several hematopoietic lineages, including megakaryocytes. Some transcription factors bind to naked DNA and chromatin with different affinities, while others do not. In the present study we used the megakaryocyte-specific promoters platelet factor 4 (PF4), and glycoprotein IIb (GPIIb) as model systems to explore the properties of Ets-1 binding to chromatin. Chromatin immunoprecipitation assays indicated that Ets-1 binds to proximal regions in the PF4 and GPIIb promoters in vivo. In vitro and in vivo experiments showed that Ets-1 binding to chromatin on lineage-specific promoters does not require lineage-specific factors. Moreover, this binding shows the same order of affinity as the binding to naked DNA and does not require ATP-dependent or Sarkosyl-sensitive factors. The effect of Ets-1 binding on promoter activity was examined using the PF4 promoter as a model. We identified a novel Ets-1 site (at -50), and a novel Sarkosyl-sensitive DNase I-hypersensitive site generated by Ets-1 binding to chromatin, which significantly affect PF4 promoter activity. Taken together, our results suggest a model by which Ets-1 binds to chromatin without the need for lineage-specific accessory factors, and Ets-1 binding induces changes in chromatin and affects transactivation, which are essential for PF4 promoter activation.

Adenosine Triphosphate↗
PubMed2004

[Analysis on the trend of long-term change of blood pressure in hypertensive patients treated with benazepril].

OBJECTIVE: To introduce the application of mixed linear model in the analysis of secular trend of blood pressure under antihypertensive treatment. METHODS: A community-based postmarketing surveillance of benazepril was conducted in 1831 essential hypertensive patients (age range from 35 to 88 years) in Shanghai. Data of blood pressure was analyzed every 3 months with mixed linear model to describe the secular trend of blood pressure and changes of age-specific and gender-specific. RESULTS: The changing trends of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found to fit the curvilinear models. A piecewise model was fit for pulse pressure (PP), i.e., curvilinear model in the first 9 months and linear model after 9 months of taking medication. Both blood pressure and its velocity gradually slowed down. There were significant variation for the curve parameters of intercept, slope, and acceleration. Blood pressure in patients with higher initial levels was persistently declining in the 3-year-treatment. However blood pressures of patients with relatively low initial levels remained low when dropped down to some degree. Elderly patients showed high SBP but low DBP, so as with higher PP. The velocity and sizes of blood pressure reductions increased with the initial level of blood pressure. CONCLUSION: Mixed linear model is flexible and robust when applied to the analysis of longitudinal data but with missing values and can also make the maximum use of available information.

Adult↗
PubMed2004

[Postmarketing surveillance on Benazepril].

OBJECTIVE: To investigate the long-term effect, safety and tolerability of benazepril in general hypertensive patients. METHODS: We conducted a three-year community-based postmarketing surveillance on benazepril among 1831 essential hypertensive patients (age range from 35 to 88 years) in Shanghai. RESULTS: 74.3% of patients persisted in medication taking and were with optimal compliance in a 3-year-follow-up program. Among those taking medication as prescribed after 3 years, 75.7% of them attained systolic blood pressure (SBP) target level of 140 mm Hg (1 mm Hg = 0.133 kPa), 87.4% attained diastolic blood pressure (DBP) target level of 90 mm Hg, and 71.5% attained total target level of 140/90 mm Hg. The reductions were approaching 15 mm Hg for SBP, 10 mm Hg for DBP, and 5 mm Hg for pulse pressure (PP) during the 3 year period. No serious adverse drug reactions (ADRs) were detected during the 3 years follow-up. Cough was the most common ADR. The cumulative incidence of benazepril related cough was 23.6% in women, significant higher than in men (18.8%). CONCLUSION: Benazepril was safe and tolerable when applied in hypertensive patients.

Adult↗
PubMed2004

[The Elp4 subunit of human Elongator complex partially complements the growth defects of yeast ELP4 deletion strain].

In this study, we performed in vivo experiments to determine the function of human Elongator subunit Elp4 by using a yeast complementary system. Our results indicated that though human ELP4 was not able to complement the growth defects of the ELP4 deletion mutant strain to high concentration salt, it partially reduced the sensitivity of mutant strain to caffeine, high temperature and 6-AU. Gene expression analysis indicated that human ELP4 partially resumed the slow activation of the PHO5 gene caused by the deletion of yELP4 under the low phosphate concentration. Meanwhile, under the condition of heat shock treatment, hELP4 increased the expression level of SSA3 gene. All these data demonstrated that human ELP4 can partially complement the growth defects and restore the slow activation of certain genes of the yELP4 deletion strain. These results indicate that human Elp4 subunit has similar functions to that of the yeast.

Acid Phosphatase↗
PubMed2004

[The survey of Cryptosporidium infection among young children in kindergartens in Anhui Province].

OBJECTIVE: To study the cryptosporidiosis infection among young children in 29 kindergartens in the province, and to explore the best way to diagnose the infection. METHODS: Stool specimens of 1204 children were collected, oocysts of Cryptosporidium were identified with auramine O-modified staining, acid-fast staining, safranine T and methylene blue staining, and auramine O-modified acid-fast staining. RESULTS: The detection rate of Cryptosporidium in four stainings were 2.46%, 1.50%, 1.98% and 3.46% respectively, and the rate was significantly higher by auramine O-modified acid-fast staining than other stainings (P < 0.01). The infection rate was significantly lower in urban children (2.14%, 15/684) than the rural ones (5.19%, 27/520). Boys and girls showed similar detection rate (1.99%, 24/1204 vs 1.50%, 18/1204). Cryptosporidium infection was usually subclinical, the major clinical features of cryptosporidium included benign diarrhea, mild abdominal pain and nausea. CONCLUSION: The Cryptosporidium infection was relatively common in kindergartens in Anhui and higher infection rate was found in rural children. As majority of the Cryptosporidium infections are subclinical, the confirmation of diagnosis is important though difficult.

Animals↗
PubMed2003

[Heritability of insulin sensitivity in twins].

OBJECTIVE: To explore the contribution of genetic and environmental effects to insulin sensitivity. METHODS: The insulin sensitivity of 249 pairs of twins was estimated by use of logarithm transformed homeostasis model assessment (HOMA), of whom 169 pairs were monozygous and 80 pairs dizygous. To formulate a univariate genetic model for the variation of insulin sensitivity, the relative influences of gene and environment on the insulin sensitivity were divided into four contributing components as A (additive effects of alleles),D (dominance effects) C (common environmental effects) and E (specific environmental effects). Heritability of insulin sensitivity was estimated by maximum likelihood method, which included the influences of age and sex on model. RESULTS: The influence of age on insulin sensitivity was not significant chi(2)=1.851 P=0.604 . The AE-model fitted the data best. The heritability of insulin sensitivity was 0.35 in males and 0.46 in females, respectively. CONCLUSION: 35% of the variance in insulin sensitivity was due to additive effects in males and 46% due to additive effects in females in this twin study.

Adult↗