Search PubMed⌕ Search

Biomedical subjects

J L Chen

Publications and source records attributed to J L Chen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Endothelin-1 stimulates leptin production in adipocytes.

Leptin is an adipocyte-derived hormone that regulates body fat stores and feeding behavior. In an effort to identify endogenous diffusible modulators of leptin production, we found that endothelin-1 (ET-1) up-regulates leptin expression in adipocytes. ET-1 is as potent and efficacious as insulin in stimulating leptin production in two different adipocyte cell lines. Endothelins stimulate leptin production via the endothelin-A receptor (ET(A)), as judged by a potency rank order of ET-1 ET-3. We detected expression of ET(A) but not ET(B) in both cell lines by Northern blot analysis. In addition, the ET(A)-selective antagonist FR139317 inhibited ET-1-induced leptin expression more potently than did the ET(B)-selective antagonist BQ788. ET-1 and insulin positively interact with each other in increasing leptin production in adipocytes. In primary mouse white fat cells, we detected expression of both ET(A) and ET(B) by Northern blot and in situ hybridization analyses. We conclude that ET-1 stimulates leptin production via the ET(A) receptor in cultured adipocytes.

Adipocytes↗
PubMed2001

Human CD1d-glycolipid tetramers generated by in vitro oxidative refolding chromatography.

CD1 molecules are specialized in presenting lipids to T lymphocytes, but identification and isolation of CD1-restricted lipid specific T cells has been hampered by the lack of reliable and sensitive techniques. We here report the construction of CD1d-glycolipid tetramers from fully denatured human CD1d molecules by using the technique of oxidative refolding chromatography. We demonstrate that chaperone- and foldase-assisted refolding of denatured CD1d molecules and beta(2)-microglobulin in the presence of synthetic lipids is a rapid method for the generation of functional and specific CD1d tetramers, which unlike previously published protocols ensures isolation of CD1d tetramers loaded with a single lipid species. The use of human CD1d-alpha-galactosylceramide tetramers for ex vivo staining of peripheral blood lymphocytes and intrahepatic T cells from patients with viral liver cirrhosis allowed for the first time simultaneous analysis of frequency and specificity of natural killer T cells in human clinical samples. Application of this protocol to other members of the CD1 family will provide powerful tools to investigate lipid-specific T cell immune responses in health and in disease.

Animals↗
PubMed2001

Directed mutagenesis of apecific active site residues on Fibrobacter succinogenes 1,3-1,4-beta -D-glucanase significantly affects catalysis and enzyme structural stability.

The functional and structural significance of amino acid residues Met(39), Glu(56), Asp(58), Glu(60), and Gly(63) of Fibrobacter succinogenes 1,3-1,4-beta-d-glucanase was explored by the approach of site-directed mutagenesis, initial rate kinetics, fluorescence spectroscopy, and CD spectrometry. Glu(56), Asp(58), Glu(60), and Gly(63) residues are conserved among known primary sequences of the bacterial and fungal enzymes. Kinetic analyses revealed that 240-, 540-, 570-, and 880-fold decreases in k(cat) were observed for the E56D, E60D, D58N, and D58E mutant enzymes, respectively, with a similar substrate affinity relative to the wild type enzyme. In contrast, no detectable enzymatic activity was observed for the E56A, E56Q, D58A, E60A, and E60Q mutants. These results indicated that the carboxyl side chain at positions 56 and 60 is mandatory for enzyme catalysis. M39F, unlike the other mutants, exhibited a 5-fold increase in K(m) value. Lower thermostability was found with the G63A mutant when compared with wild type or other mutant forms of F. succinogenes 1,3-1,4-beta-d-glucanase. Denatured wild type and mutant enzymes were, however, recoverable as active enzymes when 8 m urea was employed as the denaturant. Structural modeling and kinetic studies suggest that Glu(56), Asp(58), and Glu(60) residues apparently play important role(s) in the catalysis of F. succinogenes 1,3-1,4-beta-d-glucanase.

Amino Acid Sequence↗
PubMed2001

Delivery of biological performance via micro-encapsulation formulation chemistry.

Lambda-cyhalothrin micro-capsules have been prepared by a novel in situ procedure. Manipulation of the chemistry has led to slow- and fast-release formulations. The latter has a biological performance comparable to commercial lambda-cyhalothrin emulsifiable concentrates, but exhibits a significantly improved toxicological profile over EC, WP and WG formulations. Micro-encapsulation technology satisfies many of the drivers towards the safer use of pesticides.

Biological Availability↗
PubMed2001

Nuclear matrix in developing rat spermatogenic cells.

The nonchromatin structure or nuclear matrix in developing spermatogenic cells of the rat was studied using a biochemical fractionation in concert with resinless section electron microscopy. Observations demonstrated that the nuclear matrix of spermatogenic cells consisted of a three-dimensional network of filaments of variable thicknesses. In spermatogonia and spermatocytes the nuclear matrix consisted of relatively thin filaments, while that of round spermatids consisted of a thicker interconnecting network of filament. In elongating spermatids, the interior of the nuclear matrix consisted of a network of dense filaments bounded by a peripheral lamina. The protein composition of the nuclear matrix in spermatogenic cells was examined by high-resolution two-dimensional gel electrophoresis and correlated with morphological changes characteristic of each stage. The results showed that the proteins of nuclear matrix changed in a cell stage-specific manner. These stage-specific changes corresponded to the major transitions of chromatin structure and function during spermatogenesis. Furthermore, immunocytochemical and immunoblotting analysis of DNA topoisomerase II (topo II) revealed that this enzyme exhibited stage-specific variations and was associated with the nuclear matrix. These results suggest that the nuclear matrix in spermatogenic cells may be involved in mediating DNA modifications and maintaining nuclear organization during spermatogenesis. Mol. Reprod. Dev. 59:314-321, 2001.

Animals↗
PubMed2001

A genome-wide search for type II diabetes susceptibility genes in Chinese Hans.

AIMS/HYPOTHESIS: The aim of the study was to search for Type II (non-insulin-dependent) diabetes mellitus susceptibility genes in a Chinese population. METHODS: A genome-wide scan was carried out using non-parametric linkage analyses. We studied 102 families (478 family members) who were Chinese Hans residing in east and south-east China, including 282 diabetic patients, among them 142 independent affected sibpairs were available for genotyping. A total of 247 fluorescence labelled microsatellite markers, with an average resolution of 15 cM, were amplified. GENEHUNTER was used for the non-parametric linkage analyses. RESULTS: Two loci on chromosome 9 D9S171 and D9S175 showed suggestive evidence for linkage, with an NPL-score of 3.286 and 2.939 respectively, and a p value of 1.19 x 10(-4) and 4.47 x 10(-4). A locus on the long arm of chromosome 20, D20S196 showed a rise in the non-parametric-linkage score (from 1.517 to 2.922) and a corresponding decrease in the p value from 0.04 to 6.5 x 10(-4) when families with lower BMI were analysed alone. Other loci with weaker evidence for linkage were also observed. CONCLUSIONS: Our results suggest that chromosome 9 contains genes involved in the susceptibility to Type II diabetes in an eastern and southeastern Chinese Han population, and chromosome 20 could hide genes linked to Type II diabetes in families with a lower BMI. Other regions could also hide susceptibility genes with minor effects.

Body Mass Index↗
PubMed2001

Bipedal stance exercise enhances antiresorption effects of estrogen and counteracts its inhibitory effect on bone formation in sham and ovariectomized rats.

In this study we employed a raised cage model in combination with estrogen to observe their effects on the proximal tibial metaphysis (PTM) and tibial shaft (TX) in sham-operated or ovariectomized rats. A total of 105 6-month-old female Sprague-Dawley rats were used in the study. Bilateral sham ovariectomy or ovariectomy was performed at day 0 and the rats were housed in normal height or raised cages (RCs) and injected subcutaneously twice per week with 10 microg/kg of 17beta-estradiol (E2) or vehicle for 4 and 8 weeks. Because the time course of bone loss or bone gain distribution was not uniform in the metaphyses of the tibia, we subdivided the PTM into three zones (medial, central, and lateral) to observe the different bone loss or bone gain patterns after ovariectomy and/or raised cages. We found that: (1) E2 alone did not alter bone area or architecture in sham rats, whereas RC alone increased trabecular thickness and area of PTM, but had no effects on TX; (2) Ovx induced most bone loss from the central zone of the PTM and endocortical surface of TX, accompanied by decreased trabecular number and increased bone resorption; (3) E2 alone prevented ovx-induced bone loss by preserving trabecular number and depressing bone resorption; (4) RC alone partially compensated for bone loss following ovx by thickening the surviving trabeculae in lateral and medial zones, and tended to stimulate bone formation and decrease bone resorption; and (5) RC plus E2 increased trabecular bone area by having an additive effect on bone resorption and bone turnover. RCs helped to prevent the depressive effect of estrogen on periosteal bone formation. In conclusion, early and rapid bone loss occurred in the central zone of the metaphysis and endocortical surface after ovx. Estrogen replacement therapy prevented this loss. Raised cages partially compensated for bone loss following ovx by thickening the trabeculae in the lateral area of the metaphysis and decreased endocortical erosion. Combination treatment added bone to the PTM and prevented the decrease of periosteal bone formation after estrogen administration.

Animals↗
PubMed2001

Differential gene expression in a DNA double-strand-break repair mutant XRS-5 defective in Ku80: analysis by cDNA microarray.

The ability of cells to rejoin DNA double-strand breaks (DSBs) usually correlates with their radiosensitivity. This correlation has been demonstrated in radiosensitive cells, including the Chinese hamster ovary mutant XRS-5. XRS-5 is defective in a DNA end-binding protein, Ku80, which is a component of a DNA-dependent protein kinase complex used for joining strand breaks. However, Ku80-deficient cells are known to be retarded in cell proliferation and growth as well as other yet to be identified defects. Using custom-made 600-gene cDNA microarray filters, we found differential gene expressions between the wild-type and XRS-5 cells. Defective Ku80 apparently affects the expression of several repair genes, including topoisomerase-I and -IIA, ERCC5, MLH1, and ATM. In contrast, other DNA repair-associated genes, such as GADD45A, EGR1 MDM2 and p53, were not affected. In addition, for large numbers of growth-associated genes, such as cyclins and clks, the growth factors and cytokines were also affected. Down-regulated expression was also found in several categories of seemingly unrelated genes, including apoptosis, angiogenesis, kinase and signaling, phosphatase, stress protein, proto-oncogenes and tumor suppressors, transcription and translation factors. A RT-PCR analysis confirmed that the XRS-5 cells used were defective in Ku80 expression. The diversified groups of genes being affected could mean that Ku80, a multi-functional DNA-binding protein, not only affects DNA repair, but is also involved in transcription regulation. Our data, taken together, indicate that there are specific genes being modulated in Ku80- deficient cells, and that some of the DNA repair pathways and other biological functions are apparently linked, suggesting that a defect in one gene could have global effects on many other processes.

Animals↗
PubMed2001

The lipophilicity, pharmacokinetics, and cellular uptake of different chemically-modified tetracyclines (CMTs).

CMTs are analogs of tetracyclines, which are chemically modified to eliminate their antimicrobial efficacy but which retain their inhibitory activity against matrix metalloproteinases. These compounds have been found to inhibit connective tissue breakdown in animal models of diseases such as periodontitis, arthritis and cancer. Because CMTs exhibit different in vivo efficacy in these various models of disease, the current study compared their pharmacokinetics and other properties as follows: Adult male Sprague-Dawley rats were administered by oral gavage a single dose of 5mg of different CMTs suspended in 1 ml 2% carboxymethyl-cellulose, and blood samples were collected from 1-48 hours after dosing. The sera were extracted, then analyzed by HPLC using a C-18 reverse-phase column. The results showed that the peak concentrations (C(max)) in rat sera 1-12 hours after oral administration of CMTs -1, -2,-3, -4,-5,-6,-7,-8 and doxycycline were 5.5, 0.7, 4.6, 6.2, 0.8, 0.7, 9.0 (note: the 3 peaks detected for CMT-7 were combined), 15.0 and 0.9 microg/ml, respectively. Their in vivo half-lives (t(1/2)) were 11, 5, 22, 11, 32, 15, 37, 38, and 17 hours, respectively. Of the anticollagenase CMTs tested, CMT-8 showed the greatest C(max) and t(1/2)values, followed by CMTs-3, -1, -4, and perhaps -7; CMTs-2, -5, and -6 exhibited much lower levels in serum. The relative lipophilicities of the 8 CMTs and doxycycline were tested by examining their extractability in octanol. The results showed that CMT-2, -5, and -6 had the lowest partition coefficients using this organic solvent, while CMT-3 was the most lipophilic. The lipophilicity of the different CMTs was also positively correlated (r(2)=0.767, P<0.05) to peak serum concentrations (C(max)), but not to their serum half-lives (r(2)=0.25,P=0.49). This property of the different CMTs was also found to be positively correlated to their ability to enter into human whole blood cells in vitro (r2=0.95, P<0.001). Since CMT-8, as well as CMTs-3 and -1, consistently exhibited the greatest in vivo efficacy in animal models of tissue breakdown, this may reflect, at least in part, their favorable pharmacokinetics and tissue uptake.

Administration, Oral↗
PubMed2001

Intracranial bone marrow transplantation after traumatic brain injury improving functional outcome in adult rats.

OBJECT: The authors tested the hypothesis that intracranial bone marrow (BM) transplantation after traumatic brain injury (TBI) in rats provides therapeutic benefit. METHODS: Sixty-six adult Wistar rats, weighing 275 to 350 g each, were used for the experiment. Bone marrow prelabeled with bromodeoxyuridine (BrdU) was harvested from tibias and femurs of healthy adult rats. Other animals were subjected to controlled cortical impact, and BM was injected adjacent to the contusion 24 hours after the impact. The animals were killed at 4, 7, 14, or 28 days after transplantation. Motor function was evaluated both before and after the injury by using the rotarod test. After the animals had been killed, brain sections were examined using hemotoxylin and eosin and immunohistochemical staining methods. Histological examination revealed that, after transplantation, BM cells survived, proliferated, and migrated toward the injury site. Some of the BrdU-labeled BM cells were reactive, with astrocytic (glial fibrillary acid protein) and neuronal (NeuN and microtubule-associated protein) markers. Transplanted BM expressed proteins phenotypical of intrinsic brain cells, that is, neurons and astrocytes. A statistically significant improvement in motor function in rats that underwent BM transplantation, compared with control rats, was detected at 14 and 28 days posttransplantation. CONCLUSIONS: On the basis of their findings, the authors assert that BM transplantation improves neurological outcome and that BM cells survive and express nerve cell proteins after TBI.

Animals↗
PubMed2001

[The advancement of G protein and coupled signal transduction pathways].

G protein coupled signal transduction system is one major transmembrane signaling pathways in cell. Research of biochemistry and pharmacology in medicine showed that a lot of medicines play their role through G protein coupled signaling pathways. Thus, systematic study on G protein structure and functions had very important effects on new medicine producing. In the process of creature evolution, there are highly conserved amino-acid sequences in G protein. Study on G protein and coupled signal components in plants and insects signaling processes may benefit to determine the mechanism of crop resistance to disease and pest insect and resistant chemicals effect on insect behavior and physiology. This paper reviews the research progress and prospect of practical use in recent studies of G protein and coupled components in animal, insect and plant signaling pathways.

Animals↗
PubMed2001

Sequential changes of gastric hyperplastic polyps following endoscopic ligation.

BACKGROUND: Endoscopic ligation has been extensively applied in the management of esophageal and gastric varices with or without bleeding. The varices are automatically eradicated through the use of ligation. However, whether avascular necrosis will occur in a gastrointestinal polyp when the base is ligated remains unclear. The aims of this pilot study were to investigate the sequential changes of gastric hyperplastic polyps following endoscopic detachable snare ligation and to determine the possibility of induction of avascular necrosis in these lesions following ligation. METHODS: Eleven patients with eighteen gastric hyperplastic polyps were treated with endoscopic detachable-snare ligation. The polyps were observed for 5 minutes and biopsies were then conducted. At 14 days after endoscopic ligation, follow-up endoscopies were performed to assess the outcome of the strangulated polyps. RESULTS: After being strangulated by the detachable snares, a majority of the polyps immediately congested (94%), and then developed cyanotic change (89%) approximately 4 minutes later. Pathological examination revealed severe venous congestion in the lamina propria of the strangulated polyps. On follow-up endoscopy 2 weeks later, all the snares had dropped off, and avascular necrosis occurred in sixteen polyps (89%). All of the polyps with avascular necrosis were detected to have developed cyanotic changes in initial endoscopy. No complications occurred during or following the ligation procedure. CONCLUSIONS: Most gastric hyperplastic polyps develop avascular necrosis following ligation by detachable snare. Cyanotic change is an important predictor of the outcomes of the lesions following endoscopic ligation. The application of this ligation technique in treatment of bleeding or non-bleeding gastrointestinal polyps deserves further investigation.

Adolescent↗
PubMed2001

[Comparative effects of carvedilol and metoprolol in preventing from left ventricular remodeling after acute myocardial infarction in rats].

OBJECTIVE: To compare the effects of carvedilol and metoprolol in preventing from left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats. METHODS: Twenty-four hours after ligating left coronary artery, 105 surviving female SD rats were randomly assigned to AMI control, carvedilol 1 mg/(kg.d) and metoprolol 2 mg/(kg.d) groups. Sham-operated rats (n = 16) were selected randomly as non-infarction control. After four weeks of drugs therapy, hemodynamic studies and pathologic analysis were performed. Exclusive of MI size < 35% or > 55%, complete experimental variables were obtained in 46 rats, which were comprised of AMI (n = 11), carvedilol (n = 12), metoprolol (n = 11), and Sham-operated (n = 12) groups. RESULTS: Compared with sham-operated group, left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV) and weight (LVW), were all significantly increased (P < 0.05-0.001), while maximal rate of rise and fall (+/- dp/dt) of LV pressure as well as their corrected values (+/- dp/dt/LVSP) were all significantly decreased (P < 0.01-0.001) in AMI group. In comparison with AMI group, the LVEDP and LVV were all significantly decreased (all P < 0.001), while +/- dp/dt and +/- dp/dt/LVSP were significantly increased (P < 0.05-0.001) in both carvedilol and metoprolol group, with LVW and RVW only decreased in carvedilol group (P < 0.05-0.01). CONCLUSIONS: 1. Carvedilol can effectively attenuate LVRM, and improve hemodynamics and LV function after AMI in rats, 2. Metoprolol has equivalent beneficial effects as carvedilol on hemodynamics, LV dilatation and function, but not LV hypertrophy.

Adrenergic beta-Antagonists↗
PubMed2001

A novel method to 'exercise' rats: making rats rise to erect bipedal stance for feeding - raised cage model.

We employed a novel method to exercise rats: making them rise to bipedal stance for feeding using raised cages. We studied its effects on the skeletons of 6 and 10-month-old intact or orchidectomized (ORX) rats. Body and hindlimb muscle weights, tibial BMC and periosteal cortical bone formation increased after housing in raised cages, but more so in 6-month-old animals than in 10-month-old ones. In 6-month-old orchidectomized rats, raised cages partially prevented ORX-induced bone loss by stimulating periosteal cortical bone (TX) formation and decreased bone resorption next to marrow. In 10-month-old male orchidectomized rats, raised cages also decreased the endosteal and trabecular bone resorption, but not enough to prevent completely ORX-induced net bone losses. Because the osteogenic effects of raised cages alone were only partial, we also studied the interaction between raised cage and prostaglandin E(2) (PGE(2)) in 10-month-old retired female breeders. When treated with combined raised cage and PGE(2), both cortical (TX) and trabecular bone mass of the proximal tibial metaphysis and lumbar vertebral body increased over either raised cages or PGE(2) treatment alone, that was accompanied by dramatic increased bone formation at periosteal and endosteal surfaces. Thus making rats rise to erect bipedal stance for feeding helps to prevent bone loss after orchidectomy; it amplifies the anabolic effects of PGE(2), and it provides an inexpensive, non-invasive and reliable way to increase mechanical loading of certain bones of the rat skeleton.

Journal Article↗
PubMed2000

Transcription of Epstein-Barr virus-encoded nuclear antigen 1 promoter Qp is repressed by transforming growth factor-beta via Smad4 binding element in human BL cells.

In Epstein-Barr virus (EBV)-infected BL cells, the oncogenic EBV-encoded nuclear antigen 1 (EBNA 1) gene is directed from the latent promoter Qp. Yeast one-hybrid screen analysis using the -50 to -37 sequence of Qp as the bait was carried out to identify transcriptional factors that may control Qp activity. Results showed that Smad4 binds the -50 to -37 sequence of Qp, indicating that this promoter is potentially regulated by TGF-beta. The association of Smad4 with Qp was further confirmed by supershift of EMSA complexes using Smad4-specific antibody. The transfection of a Qp reporter construct in two EBV(+) BL cell lines, Rael and WW2, showed that Qp activity is repressed in response to the TGF-beta treatment. This repression involves the interaction of a Smad3/Smad4 complex and the transcriptional repressor TGIF, as determined by cotransfection assay and coimmunoprecipitation analysis. Results suggest that TGF-beta may transcriptionally repress Qp through the Smad4-binding site in human BL cells.

Burkitt Lymphoma↗
PubMed2000

Novel antihyperglycemic terpenoid-quinones from Pycnanthus angolensis.

Two new compounds, pycnanthuquinone A (1) and pycnanthuquinone B (2), were isolated from leaves and stems of the African plant, Pycnanthus angolensis (Welw.) Warb (Myristicaceae), by bioassay-guided fractionation of an ethanolic extract using a diabetic mouse model. Pycnanthuquinones A and B are the first representatives of a novel terpenoid-type quinone skeleton, and both compounds possess significant antihyperglycemic activity.

Africa↗
PubMed2000

Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning.

The primary neuroendocrine interface, hypothalamus and pituitary, together with adrenals, constitute the major axis responsible for the maintenance of homeostasis and the response to the perturbations in the environment. The gene expression profiling in the human hypothalamus-pituitary-adrenal axis was catalogued by generating a large amount of expressed sequence tags (ESTs), followed by bioinformatics analysis (http://www.chgc.sh.cn/ database). Totally, 25,973 sequences of good quality were obtained from 31,130 clones (83.4%) from cDNA libraries of the hypothalamus, pituitary, and adrenal glands. After eliminating 5,347 sequences corresponding to repetitive elements and mtDNA, 20,626 ESTs could be assembled into 9, 175 clusters (3,979, 3,074, and 4,116 clusters in hypothalamus, pituitary, and adrenal glands, respectively) when overlapping ESTs were integrated. Of these clusters, 2,777 (30.3%) corresponded to known genes, 4,165 (44.8%) to dbESTs, and 2,233 (24.3%) to novel ESTs. The gene expression profiles reflected well the functional characteristics of the three levels in the hypothalamus-pituitary-adrenal axis, because most of the 20 genes with highest expression showed statistical difference in terms of tissue distribution, including a group of tissue-specific functional markers. Meanwhile, some findings were made with regard to the physiology of the axis, and 200 full-length cDNAs of novel genes were cloned and sequenced. All of these data may contribute to the understanding of the neuroendocrine regulation of human life.

Alternative Splicing↗