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Min Chen

Publications and source records attributed to Min Chen.

At least 217 records · Page 12Linked to original sources
PubMed2002

Activation of initiator caspases through a stable dimeric intermediate.

Structural and biochemical studies have revealed that procaspases form dimers prior to proteolytic activation. How the two procaspases interact in the dimer is unclear. To study the mechanisms of dimer-dependent caspase activation we used a heterodimeric system so that two caspase molecules can be specifically brought together. Surprisingly, only one caspase partner in the dimer needs to be enzymatically active for caspase processing and activation to occur. Caspase activation is inefficient in the dimer in the absence of intramolecular processing, suggesting that caspase activation is initiated via intramolecular processing. Homodimerization of caspase-8 or caspase-9 leads to the formation of a stable dimeric complex. However, heterodimerization between caspase-8 and caspases-3, -9, or -10 failed to induce stable dimer formation or caspase activation. Our data suggest that the formation of a stable dimeric intermediate initiates caspase activation.

Caspase 3↗
PubMed2002

Effect of bowel resection and high-fat diet on heart CD36/fatty-acid translocase expression in a rat model of short-bowel syndrome.

Long-chain fatty acids (LCFA) are the major energy substrates for the heart. In short-bowel syndrome (SBS), LCFA delivery to the myocardium decreases due to fat malabsorption. Fatty-acid translocase (FAT)/CD36 has recently been identified as a LCFA-binding protein in heart tissue. To determine the effects of bowel resection and a high-fat diet (HFD) on myocardial CD36 expression, male Sprague-Dawley rats were randomly assigned to one of three groups: sham rats fed normal chow (Sham-NC); SBS rats fed NC (SBS-NC), and SBS rats fed a HFD (SBS-HFD). Control rats underwent transection and anastomosis; SBS animals underwent 75% small-bowel resection. Rats were killed at 3 or 14 days. Total body weight, heart weight, heart-tissue total lipid, serum cholesterol, and triglycerides were determined at death. Total RNA from the myocardium was extracted using TRIZOL reagent. Northern-blot analysis was used to determine FAT/CD36 mRNA. Statistical significance was determined by Student's t-test with P values below 0.05 considered significant. SBS-NC and SBS-HFD rats had significantly lower body weights compared with Sham-NC animals. The heart weights and myocardial total lipid did not vary among experimental groups. Decreases in plasma triglycerides (38.2 +/- 3.8 vs 58.8 +/- 5.5 mg/dl, P < 0.05) and cholesterol (38.2 +/- 6.9 vs 55.3 +/- 8.2 mg/dl, P < 0.05) in SBS-NC compared to Sham-NC rats on day 3 was accompanied by a twofold increase ( P < 0.05) in myocardial CD36/FAT mRNA levels. Early exposure to HFD led to increased (vs SBS-NC) plasma cholesterol (82.9 +/- 5.7 vs 38.2 +/- 6.9 mg/dl, P < 0.05) and triglycerides (62.5 +/- 15.6 vs 38.2 +/- 3.8 mg/dl, P < 0.05), and a concomitant decrease in CD36/FAT mRNA levels (45.1 +/- 17.8 vs 86.6 +/- 15%, respectively, P < 0.05). Plasma lipid concentration and myocardial CD36/FAT mRNA levels on day 14 were not significantly different among the experimental groups. In this rat model of SBS, the heart thus reacts to decreased LCFA delivery by increased tissue CD36/FAT mRNA levels and, consequently, active LCFA uptake. A HFD increased plasma lipid concentrations and decreased CD36/FAT levels.

Animals↗
PubMed2002

Calpain and mitochondria in ischemia/reperfusion injury.

Studies of ischemia/reperfusion (I/R) injury and preconditioning have shown that ion homeostasis, particularly calcium homeostasis, is critical to limiting tissue damage. However, the relationship between ion homeostasis and specific cell death pathways has not been investigated in the context of I/R. Previously we reported that calpain cleaved Bid in the absence of detectable caspase activation (1). In this study, we have shown that an inhibitor of the sodium/hydrogen exchanger prevented calpain activation after I/R. Calpain inhibitors prevented cleavage of Bid as well as the downstream indices of cell death, including DNA strand breaks, creatine kinase (CK) release, and infarction measured by triphenyl tetrazolium chloride (TTC) staining. In contrast, the broad spectrum caspase inhibitor IDN6734 was not protective in this model. To ascertain whether mitochondrial dysfunction downstream of these events was a required step, we utilized a peptide corresponding to residues 4-23 of Bcl-x(L) conjugated to the protein transduction domain of HIV TAT (TAT-BH4), which has been shown to protect mitochondria against Ca2+-induced deltaPsi(m) loss (2). TAT-BH4 attenuated CK release and loss of TTC staining, demonstrating the role of mitochondria and a pro-apoptotic Bcl-2 family member in the process leading to cell death. We propose the following pathway. (i) Reperfusion results in sodium influx followed by calcium accumulation. (ii) This leads to calpain activation, which in turn leads to Bid cleavage. (iii) Bid targets the mitochondria, causing dysfunction and release of pro-apoptotic factors, resulting in DNA fragmentation and death of the cell. Ischemia/reperfusion initiates a cell death pathway that is independent of caspases but requires calpain and mitochondrial dysfunction.

Animals↗
PubMed2002

Molecular determinants of human melanocortin-4 receptor responsible for antagonist SHU9119 selective activity.

The hypothalamic melanocortin-4 receptor (MC4R), a seven transmembrane G-protein-coupled receptor, plays an important role in the regulation of body weight. The synthetic melanocortin analog SHU9119 has been widely used to characterize the physiological role of MC4R in feeding behavior and energy homeostasis. Previous studies indicated that SHU9119 is an agonist at the melanocortin-1 receptor (MC1R) but an antagonist at the MC4R. However, the molecular basis of the interaction between hMC4R and SHU9119 has not been clearly defined. To gain insight into the molecular determinants of hMC4R in the selectivity of SHU9119 chimeras and mutants hMC1R and hMC4R were expressed in cell lines and pharmacologically analyzed. A region of receptor containing the third transmembrane of hMC4R was found to be required for selective SHU9119 antagonism. Further mutagenesis studies of this region of hMC4R demonstrated that the amino acid residue leucine 133 in the third transmembrane was critical for the selective antagonist activity of SHU9119. The single substitution of leucine 133 to methionine did not affect SHU9119 binding to hMC4R. However, this substitution did convert SHU9119 from an antagonist to an agonist. Conversely, exchange of Met(128) in hMC1R to Leu, the homologous residue 133 of hMC4R, displayed a reduction in SHU9119 binding affinity and potency. This report provides the details of the molecular recognition of SHU9119 antagonism at hMC4R and shows that amino acid Leu(133) of hMC4R plays a key role in melanocortin receptor subtype specificity.

Amino Acid Sequence↗
PubMed2002

The major light-harvesting pigment protein of Acaryochloris marina.

The major light-harvesting protein complex containing chlorophyll (Chl) d was isolated from Acaryochloris marina thylakoid membranes. Isolation was achieved by detergent solubilisation followed by separation on 6-40% sucrose gradients using ultracentrifugation. The best Chl d yield (70%) used 0.3% dodecyl maltoside, 0.15% octyl glucoside, 0.05% zwittergent 3-14 with the detergent:total Chl d ratio around 10:1 (w/w). Characterisation of the light-harvesting pigment protein complex (lhc) involved non-denaturing electrophoresis, SDS-PAGE, absorbance and fluorescence spectroscopy. The main polypeptide in the lhc was shown to be ca. 34 kDa and to contain Chl d and Chl a, indicating that the Acaryochloris lhc is similar to that of prochlorophytes. The Chl a level varied with the culture conditions, which is consistent with previous findings.

Bacterial Proteins↗
PubMed2002

The effect of ethnic origin on nuchal translucency at 10-14 weeks of gestation.

INTRODUCTION: Fetal nuchal translucency (NT) increases with gestation and is affected by fetal posture and fetal gender. A recent report suggested that there might also be ethnic differences. We investigated the effect of ethnic origin on NT in an Asian population. METHODS: NT was measured at 10-14 weeks. The measurements were converted into multiples of the median (MoM) for gestational day. The risk of Down syndrome was calculated by combining NT and maternal age. Cases affected by chromosomal and major structural abnormalities were excluded. NT measurements of different ethnic groups were compared. RESULTS: Between January 1997 and October 2001, 16 981 pregnancies with known ethnic origin and normal fetal outcome were analysed. Median NT MoM (95% CI) of the Filipinos was 1.07 (1.04-1.11). This was significantly higher than that of the Chinese, 1.01 (1.01-1.02); other Asians (Indians, Pakistanis and Nepalese), 0.96 (0.94-0.99), and Caucasians, 0.98 (0.93-1.06) (p<0.05, respectively; Mann-Whitney U-test). An NT risk cut-off of 1:180 would classify 5% of the Chinese, 4.6% of the Caucasians, 5.6% of the Filipinos and 4.2% of the other Asians as screen-positive. There were no statistically significant differences between these screen-positive rates (p>0.05, Chi-square test). CONCLUSIONS: Although there were statistically significant differences in NT measurements between different ethnic groups, it was clinically insignificant, as reflected by similar screen-positive rates.

Adult↗
PubMed2002

Attitude of at-risk subjects towards preimplantation genetic diagnosis of alpha- and beta-thalassaemias in Hong Kong.

OBJECTIVES: The aim of the study was to assess whether preimplantation genetic diagnosis (PGD) was an acceptable alternative to prenatal diagnosis in couples at risk of giving birth to a child with alpha- or beta-thalassaemia in an Asian population. METHODS: An information leaflet was distributed to the women at risk. They were asked to complete a questionnaire after having an interview with a designated investigator. RESULTS: A total of 141 valid questionnaires were analysed; 82.3% of the women considered PGD either the same or better than conventional prenatal diagnosis. Women with an affected child or a subfertility problem were more willing to accept PGD and to undergo this procedure in their future pregnancies. Their main concern about PGD was damage to the embryo during the PGD procedure. The most important perceived advantage of PGD was avoidance of termination of an affected pregnancy. CONCLUSIONS: PGD is an acceptable alternative to conventional prenatal diagnosis in women at risk of giving birth to a child with alpha- or beta-thalassaemia in an Asian population. This is particularly true in women with a subfertility problem and in women who already have an affected child.

Adult↗
PubMed2002

Sonographic features of ileal duplication cyst at 12 weeks.

Enteric duplication cyst is a congenital abnormality that is believed to arise from abnormal recanalization of the bowel during embryogenesis. Previous reports suggest that the condition may be suspected prenatally by sonographic demonstration of an intra-abdominal cystic mass in the second and third trimesters. We present the sonographic features of a fetus with ileal duplication cyst at 12 weeks of gestation, which show that the condition may present in the first trimester of pregnancy.

Adult↗
PubMed2002

Regulation of CD36 expression in human melanoma cells.

BACKGROUND: CD36 is a suspected facilitator of long chain fatty acid transport and as a thrombospondin (TSP) receptor, thereby being implicated in cell proliferation, angiogenesis and tumor metastasis. The human amelanotic melanoma cell line, C32, is known to express CD36 and has been as a model for studying TSP binding. PURPOSE: The purpose of this study was to investigate the regulation of CD36 expression in the C32 cell line. METHOD: C32 cells were treated with 12-O-tetradecanoylphorobol-13-acetate (TPA)(10 microM), insulin (174 nM), ibuprofen (0.3 mM) and oleic acid. CD36 mRNA levels were determined by Northern Blot analysis using human CD36 cDNA probe. Western blot analysis utilized the human anti-CD36 antibody. Protein and mRNA concentration was determined by autoradiography, densitometry and NIH image software. Statistical analysis was by Student's t-test with P < 0.05 considered significant. RESULTS: CD36 mRNA levels were decreased 2.2 fold in C32 cells treated with TPA (p < 0.05) compared to control cells. Insulin treated cells showed a 30% increase (p < 0.05) in CD36 mRNA levels. Ibuprofen, a regulator of peroxisomal proliferation activated receptor (PPAR) alpha, was found to increase CD36 protein levels by 50% (p < 0.05). Oleic acid had no effect on CD36 mRNA or protein levels. CONCLUSION: The finding that the tumor promoter TPA significantly decreases CD36 mRNA levels, while insulin and ibuprofen increase CD36 expression, may have important implications in tumor biology. The regulation of CD36 expression in tumor cells may play an important role in tumor growth, metastasis and angiogenesis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Adrenal cortical and medullar hyperplasia--a retrospective analysis of 6 cases.

The features of the symptoms, laboratory tests and pathological characteristics of adrenal cortical and medullary hyperplasia were studied. In 6 cases of hypercatecholaminenia, plasma norepinephrine (NE), epinephrine (E), catecholamine (CA) and 24-h urinary vanillylmandelic acid (VMA), 17-hydroxycorticosteroid (OHCS) and 17-ketosteroid (KS) were determined. Adrenal glands were examined by CT scan and 131I-MIBG imaging. Pathological examination was performed after operation. The results showed that in 6 cases of hypercatecholaminenia (3 men and 3 women) aged from 34-50 years, the clinical features were just like "pheochromocytoma", for example, episodic headache, perspiration, palpitation, pallor, apprehension, nausea, tremor, anxiety and so on. Plasma levels of CA, NE and E were elevated in all 6 cases. 24-h urinary samples obtained at the onset revealed elevated VMA in 1 case. 24-h urinary cortisol was obviously elevated in all 6 cases. 24-h urinary 17-OHCS, 17-KS was normal. B-type ultrasound, CT, MRI and 131I-MIBG revealed 9 lateral adrenal gland diffuse or nodular enlargement in 6 cases. Pathologic examination showed adrenal cortical and medullary hyperplasia. Clinically, adrenal cortical and medullary hyperplasia resembled "pheochromocytoma". The most significant feature of this disease was both elevated plasma CA and 24-h urinary cortisol obviously. Pathologic examination showed adrenal cortex nodular hyperplasia and medullar diffuse or limit hyperplasia. Whether it is an independent disease or symptoms of the other disease has not final conclusion up till now.

Adrenal Cortex↗
PubMed2002

The effect of marine colloids on the growth of photosysthetic bacteria.

Marine colloids could be an important source of nitrogen for bacteria and photoplankton. But elevated concentration of colloids may stimulate algal growth and lead to red tides in coastal waters. The effects of colloidal organic carbon (COC) concentration on the growth of photosysthetic bacteria (PSB) were investigated under different colloidal treatments in the laboratory. The PSB growth was inversely proportional to COC concentration and was restricted by high-molecular-weight (HMW) colloids (>10 KDa) in treatments with non-nutrient or just inorganic nutrient with low COC concentration ( < or = 5 microMC). However, the PBS growth was enhanced in the presence of HMW colloids in the treatment with inorganic nutrient and high COC (127 and 255 microMC) or with both inorganic nutrient and low-molecular-weight organic matter. Both bacteria number and bacteria growth ratio increased significantly when the concentration of COC was > or = 5 microMC. Our results suggest that marine colloids can be utilized by bacteria and might regulate primary productivity in coastal waters.

Bacteria↗
PubMed2002

Platinum-induced autoantibodies target nucleoplasmic antigens related to active transcription.

Research on autoimmune diseases has revealed that autoimmunity can be induced by heavy metals such as mercury and gold. Following the introduction of platinum-containing catalytic converters in automobiles, the emission of platinum compounds constitutes an abundant environmental pollutant, however, potential immunological hazards resulting from platinum-containing emissions were not yet examined. In our previous studies on molecular mechanisms of heavy metal-induced autoimmunity, we showed a platinum-dependent subcellular redistribution of the autoantigen fibrillarin from the nucleolus to the nucleoplasm. Since H-2s mice constitute a valuable model to study the role of heavy metals in the development of systemic autoimmunity, we treated susceptible B10.S mice with hexachloroplatinate (Na2PtCl6, Pt4+) to examine whether platinum induces the production of autoantibodies. The present study shows for the first time that chronic administration of Pt4+ generated an autoimmune response in mice which targets distinct nucleoplasmic antigens. Dual-labeling revealed substantial colocalization of these nucleoplasmic autoantigens with (i) nascent RNA, (ii) the active, phosphorylated form of RNA polymerase II, and partial overlap with (iii) acetylated histone 4 protein, and (iv) 20S proteasomes in dendritic cells isolated from platinum-treated mice. The results suggest that platinum elicits antibodies against antigens associated with active sites of transcription which may be subject to proteasomal processing during heavy metal-induced autoimmunity.

Animals↗
PubMed2002

Subcellular recruitment of fibrillarin to nucleoplasmic proteasomes: implications for processing of a nucleolar autoantigen.

A prerequisite for proteins to interact in a cell is that they are present in the same intracellular compartment. Although it is generally accepted that proteasomes occur in both, the cytoplasm and the nucleus, research has been focusing on cytoplasmic protein breakdown and antigen processing, respectively. Thus, little is known on the functional organization of the proteasome in the nucleus. Here we report that within the nucleus 20S and 26S proteasomes occur throughout the nucleoplasm and partially colocalize with splicing factor-containing speckles. Because proteasomes are absent from the nucleolus, a recruitment system was used to analyze the molecular fate of nucleolar protein fibrillarin: Subtoxic concentrations of mercuric chloride (HgCl(2)) induce subcellular redistribution of fibrillarin and substantial colocalization (33%) with nucleoplasmic proteasomes in different cell lines and in primary cells isolated from mercury-treated mice. Accumulation of fibrillarin and fibrillarin-ubiquitin conjugates in lactacystin-treated cells suggests that proteasome-dependent processing of this autoantigen occurs upon mercury induction. The latter observation might constitute the cell biological basis of autoimmune responses that specifically target fibrillarin in mercury-mouse models and scleroderma.

Acetylcysteine↗
PubMed2002

Gs(alpha) mutations and imprinting defects in human disease.

Gs is the ubiquitously expressed heterotrimeric G protein that couples receptors to the effector enzyme adenylyl cyclase and is required for receptor-stimulated intracellular cAMP generation. Activated receptors promote the exchange of GTP for GDP on the Gs alpha-subunit (Gs(alpha)), resulting in Gs activation; an intrinsic GTPase activity of Gs(alpha) deactivates Gs by hydrolyzing bound GTP to GDP. Mutations of Gs(alpha) residues involved in the GTPase reaction that lead to constitutive activation are present in endocrine tumors, fibrous dysplasia of bone, and McCune-Albright syndrome. Heterozygous loss-of-function mutations lead to Albright hereditary osteodystrophy (AHO), a disease characterized by short stature, obesity, and skeletal defects, and are sometimes associated with progressive osseous heteroplasia. Maternal transmission of Gs(alpha) mutations leads to AHO plus resistance to several hormones (e.g., parathyroid hormone) that activate Gs in their target tissues (pseudohypoparathyroidism type IA), while paternal transmission leads only to the AHO phenotype (pseudopseudohypoparathyroidism). Studies in both mice and humans demonstrate that Gs(alpha) is imprinted in a tissue-specific manner, being expressed primarily from the maternal allele in some tissues and biallelically expressed in most other tissues. This likely explains why multihormone resistance occurs only when Gs(alpha) mutations are inherited maternally. The Gs(alpha) gene GNAS1 has at least four alternative promoters and first exons, leading to the production of alternative gene products including Gs(alpha), XL alphas (a novel Gs(alpha) isoform expressed only from the paternal allele), and NESP55 (a chromogranin-like protein expressed only from the maternal allele). The fourth alternative promoter and first exon (exon 1A) located just upstream of the Gs(alpha) promoter is normally methylated on the maternal allele and is transcriptionally active on the paternal allele. In patients with parathyroid hormone resistance but without AHO (pseudohypoparathyroidism type IB), the exon 1A promoter region is unmethylated and transcriptionally active on both alleles. This GNAS1 imprinting defect is predicted to decrease Gs(alpha) expression in tissues where Gs(alpha) is normally imprinted and therefore to lead to renal parathyroid hormone resistance.

Animals↗
PubMed2002

Renal failure associated with the use of celecoxib and rofecoxib.

OBJECTIVE: Celecoxib and rofecoxib are two relatively new nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit the cyclo-oxygenase-2 (COX-2) isoenzyme at therapeutic concentrations. The nephrotoxic potential of selective COX-2 inhibitors has not been clearly established. This study was conducted in order to understand the association between acute renal failure and the two COX-2 inhibitors celecoxib and rofecoxib. METHODS: A search was performed in the US Food and Drug Administration's (FDA) Adverse Event Reporting System (AERS) to identify cases of renal failure submitted to the FDA. A MEDLINE search of the English language literature was also performed to identify published cases of renal failure associated with celecoxib and rofecoxib. RESULTS: One hundred twenty-two and 142 domestic US cases of celecoxib and rofecoxib-associated renal failure, respectively, were identified in the AERS database. The literature search identified 19 cases of acute renal impairment in association with celecoxib and rofecoxib. In addition, drug regulatory authorities in the UK, Canada, and Australia have received about 50 reports of renal failure with celecoxib and rofecoxib. Descriptive statistics of the AERS cases have been summarised in this report. CONCLUSIONS: Data from AERS and published case reports suggest that use of both these drugs is associated with renal effects similar to that of conventional nonselective NSAIDs. Physicians should be aware that serious or life-threatening renal failure has been reported in patients with normal or impaired renal function after short-term therapy with celecoxib and rofecoxib. Patients at greatest risk for renal injury are those with pre-existing renal impairment, heart failure, liver dysfunction, those taking diuretics and/or ACE inhibitors, and the elderly. Kidney function should be monitored closely for any signs of potential renal injuries soon after initiating treatment with these agents, especially in high-risk populations. In addition, healthcare practitioners should adequately warn patients of the signs and symptoms of serious renal toxicity, and of the need for them to see their physician promptly if they occur. Celecoxib and rofecoxib are not recommended for use in patients with advanced renal disease.

Adverse Drug Reaction Reporting Systems↗
PubMed2002

Using PCR/RFLP to detect spotted fever group rickettsia in ticks and rodents collected in Ninghua, Fujian province.

OBJECTIVE: To study the existence of natural foci of Spotted Fever in Ninghua, Fujian province. METHODS: Using DNA polymerase chain reaction and restriction endonuclease fragment length polymorphism analysis (PCR/RFLP) to detect spotted fever group rickettsiae (SFGR) in ticks and rodents. RESULTS: It was found that H. wellingtoni, H. yeni, and Dermacentor auratus were infected with Rickettsia sibirica; the DNA fragments were cloned, the PCR products from isolated strain NH-97 were antigenically and genotypically identical to Rickettsia sibirica. Rattus flavipectus were found infected with R. conorii. One of the sequeuce analysis showed that the DNA sequence was different from other SFGR and close to R. japanic. CONCLUSION: Natural foci of R. sibirica, R. sibrica, R. japanic and R.conorii are found in Ninghua, Fujian province of China.

Animals↗