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Biomedical subjects

Nan Li

Publications and source records attributed to Nan Li.

At least 91 records · Page 5Linked to original sources
PubMed2004

Mechanism of glutamine-mediated amelioration of lipopolysaccharide-induced IL-8 production in Caco-2 cells.

The mechanism of glutamine (Gln)-mediated down-regulation of inflammation in the intestine is poorly understood. We hypothesize that Gln down-regulates lipopolysaccharide (LPS)-stimulated IL-8 production in intestinal epithelial cells via transcription factors that counteract the effect of LPS-mediated increase in IL-8. Caco-2 cells were incubated with different doses of Gln with or without methionine sulfoximine (MS), an inhibitor of glutamine synthetase for 24 h before stimulation by LPS (100 microg/ml for 24 h). Inhibitors of the mitogen activated protein kinase (MAPK) family were added to cells for 1.5 h following stimulation by LPS. The p38 inhibitor SB 203580 resulted in a significant decrease in IL-8 peptide production (p < 0.01). However, p38 MAPK activity increased with Gln (p < 0.05), suggesting that this was not involved with Gln-mediated down-regulation of IL-8. Screening of 54 transcription factors demonstrated that STAT-4 was the only inflammation-related transcription factor that was up-regulated by Gln depletion and down-regulated with Gln supplementation (2-fold increase), paralleling IL-8 production. EMSA analysis confirmed these findings (3.5-fold increase). These results indicate that Gln deprivation enhances IL-8 production by Caco-2 cells after LPS stimulation and that down-regulation of IL-8 production with Gln is associated with alterations in STAT-4 transcription factor binding.

Caco-2 Cells↗
PubMed2004

Identification of an HLA-A*0201-restricted CD8+ T-cell epitope SSp-1 of SARS-CoV spike protein.

A novel coronavirus, severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV), has been identified as the causal agent of SARS. Spike (S) protein is a major structural glycoprotein of the SARS virus and a potential target for SARS-specific cell-mediated immune responses. A panel of S protein-derived peptides was tested for their binding affinity to HLA-A*0201 molecules. Peptides with high affinity for HLA-A*0201 were then assessed for their capacity to elicit specific immune responses mediated by cytotoxic T lymphocytes (CTLs) both in vivo, in HLA-A2.1/K(b) transgenic mice, and in vitro, from peripheral blood lymphocytes (PBLs) harvested from healthy HLA-A2.1(+) donors. SARS-CoV protein-derived peptide-1 (SSp-1 RLNEVAKNL), induced peptide-specific CTLs both in vivo (transgenic mice) and in vitro (human PBLs), which specifically released interferon-gamma (IFN-gamma) upon stimulation with SSp-1-pulsed autologous dendritic cells (DCs) or T2 cells. SSp-1-specific CTLs also lysed major histocompatibility complex (MHC)-matched tumor cell lines engineered to express S proteins. HLA-A*0201-SSp-1 tetramer staining revealed the presence of significant populations of SSp-1-specific CTLs in SSp-1-induced CD8(+) T cells. We propose that the newly identified epitope SSp-1 will help in the characterization of virus control mechanisms and immunopathology in SARS-CoV infection, and may be relevant to the development of immunotherapeutic approaches for SARS.

Amino Acid Sequence↗
PubMed2004

HuBMSC-MCP, a novel member of mitochondrial carrier superfamily, enhances dendritic cell endocytosis.

A novel member of mitochondrial carrier superfamily has been identified from human bone marrow stromal cells (BMSC) and designated as human BMSC-derived mitochondrial carrier protein (HuBMSC-MCP). It encodes a 321 amino-acid protein with three tandem related domains of about 100 amino acids. Each domain contains two hydrophobic stretches, which are thought to span the membrane as alpha-helices. Distant relationship analysis indicates that the protein is highly conserved between species from Caenorhabditis elegans to human. HuBMSC-MCP gene is mapped to chromosome 11p11. HuBMSC-MCP mRNA expression is detectable in various human tissues and cell lines. By confocal imaging, HuBMSC-MCP is localized to mitochondria and also detected in the pseudopodial protrusion of human breast adenocarcinoma MCF-7 cells. When transfected into dendritic cells (DC), HuBMSC-MCP could enhance DCs endocytotic capacity. Thus, HuBMSC-MCP is a phylogenetically conserved and widely expressed mitochondrial carrier protein which perhaps associates with mitochondrial oxidative phosphorylation.

Amino Acid Sequence↗
PubMed2004

Glutamine decreases lipopolysaccharide-induced intestinal inflammation in infant rats.

Using a gastrostomy-fed (GF) rat infant "pup-in-a-cup" model, the effects of protein deprivation and supplemental glutamine (Gln) and glutamate (Glu) were examined to test the hypothesis that Gln decreases the proinflammatory response induced by LPS in the developing infant rat small intestine. Four groups of 6- to 7-day-old pups were fed a rat milk substitute (RMS), one providing 100% and three providing 25% of normal protein intake for another 6 days. Two of the 25% protein-fed groups received supplemental Gln or Glu. GF and LPS treatment blunted body growth and intestinal villus height and increased intestinal cytokine-induced neutrophil chemoattractant (CINC) mRNA in the protein-deprived, non-Gln-treated group compared with mother-fed pups (P < 0.05). Gln blunted intestinal CINC mRNA (P < 0.05), but Glu did not. Intestinal CINC peptide in the LPS-treated pups provided 100 and 25% protein was elevated approximately 13-fold compared with the mother-reared pups (P < 0.001). Gln and Glu decreased intestinal CINC peptide by 73 and 80%, respectively. GF, LPS-treated pups also had a higher level of plasma CINC peptide (P < 0.05). Gln but not Glu decreased plasma CINC peptide (P < 0.05). An approximate sixfold elevation of intestinal MPO activity in the GF, LPS-treated rats was decreased by Gln and Glu by 92% (P < 0.001) and 54% (P < 0.05), respectively. Intestinal and plasma TNF-alpha were increased in GF, LPS-treated pups (P < 0.01), and Gln and Glu both blunted this increase (P < 0.05) in the intestine but not in the plasma. The results indicate that Gln decreases the LPS-induced inflammatory response in infant rat intestine under different conditions of protein intake.

Animals↗
PubMed2004

Lipid raft proteomics: analysis of in-solution digest of sodium dodecyl sulfate-solubilized lipid raft proteins by liquid chromatography-matrix-assisted laser desorption/ionization tandem mass spectrometry.

Lipid rafts are glycolipid- and cholesterol-enriched membrane microdomains implicated in membrane signaling and trafficking. The highly hydrophobic nature of lipid raft proteins pose significant problems of solubilization and recovery that hinder analysis by mass spectrometry (MS) and may under-report the composition of lipid rafts. In a previous investigation of the monocyte lipid raft in which proteins were digested with trypsin following polyacrylamide gel electrophoresis we identified 52 proteins. Here we report the development of a sodium dodecyl sulfate (SDS)-aided approach in which proteins are digested in solution and examined by high-performance liquid chromatography-matrix-assisted laser desorption/ionization-tandem mass spectrometry (HPLC-MALDI-MS/MS) using a novel LC-MALDI interface thereby circumventing the need to separate proteins on gels. Using this approach we identified 71 proteins in the lipid raft, 45 of which were not detected using in-gel digestion. Among the new proteins are alpha- and beta-tubulin, tubulinspecific chaperone A, a folding protein involved in tubulin dimer assembly, and KIF13, a microtubule motor protein indicating that proteins involved in microtubule assembly and trafficking are more readily detected using an in-solution approach. To investigate why tubulin was not identified by in-gel digestion, we compared the distribution of alpha-tubulin and the raft marker flotillin-2 in buoyant density gradients before and after separation on SDS-gels. Both proteins were present in the raft fractions, but tubulin was selectively lost following separation on SDS-gels. Assemblies of cytoskeletal proteins with lipid rafts may therefore be resolved using in-solution digestion that would be missed using gel-based approaches.

Biological Transport↗
PubMed2004

Substitutes for glutamine in proliferation of rat intestinal epithelial cells.

OBJECTIVES: Glutamine (Gln) is important for intestinal epithelial proliferation. The purpose of this study was to determine whether glutamate (Glu), a mixture of nucleotide monophosphates, arginine, or glucosamine could support proliferation of rat intestinal crypt cells (IEC-6) in the absence of Gln. METHODS: Glu with added ammonia acetate, glucosamine, arginine, and nucleotide monophosphates were tested at concentrations that were isonitrogenous with respect to Gln. To determine whether de novo synthesis of Gln was affected by these nutrients, a duplicate set of treatment groups was also tested with 1.0 mM/L of methionine sulfoximine, an inhibitor of Gln synthetase. RESULTS: Gln + methionine sulfoximine-treated cells showed suboptimal proliferation below 0.6 mM/L but normal proliferation between 0.6 and 4.0 mM/L of Gln. In the absence of exogenous Gln, isonitrogenous concentrations of Glu, glucosamine, arginine, or nucleotide monophosphates yielded similar proliferation as Gln. Cells treated with Glu, glucosamine, arginine, or nucleotide monophosphate mixture showed a decrease in proliferation compared with cells treated with Gln across all treatment doses (P < 0.03). CONCLUSIONS: The importance of these results is that, in the presence of active Gln synthetase, these nutrients can maintain intestinal epithelial proliferation similar to that observed with Gln.

Acetates↗
PubMed2004

Estimating national disability risk.

In this article, I provide a method to rebuild the active and disabled life expectancy (ALE and DLE) on the basis of 'current' death and disability risks, and to measure disability risk. This method uses national-level data, and is based on two main assumptions. The first is the Gompertz assumption that death rate rises with age exponentially, and the second is the Cox assumption that death rates of active status are proportional to those of disabled status across age. Applying this method to the US data, I find that the disability risk has increased between 1970 and 1990 for both men and women aged 40 and older. Situations in which above assumptions could be removed are also discussed.

Adult↗
PubMed2004

Effects of protein deprivation on growth and small intestine morphology are not improved by glutamine or glutamate in gastrostomy-fed rat pups.

OBJECTIVES: Critically ill neonates often have their enteral intake severely limited shortly after birth. Whether glutamine (Gln) or glutamate (Glu) can preserve intestinal structure and function in the neonate undergoing limited enteral feeding is not clear. We hypothesize that Gln and Glu can similarly preserve intestinal structure in the developing small intestine of infant rats fed a low protein diet. METHODS: Using a gastrostomy-fed "pup-in-a-cup" rat model, the effects of Gln and Glu on the developing rat small intestine were examined. Four groups of 6- to 7-day-old pups were fed rat milk substitute (RMS) via gastrostomy tube. One group was provided 100% and three were provided 25% of the protein normally received from their mothers. Two of the groups fed 25% protein received additional Gln or Glu for 6 days. RESULTS: Pups receiving the 100% protein RMS were larger than pups receiving the 25% protein RMS with or without Gln/Glu supplementation (P < 0.001). Average villus height (P < 0.01) and area (P < 0.01) were greater in pups receiving 100% protein RMS than in pups given 25% protein RMS formula. There was no significant difference among the groups in mucosal maltase or alkaline phosphatase activities. Tight junction protein claudin-1 was significantly higher in the group fed 100% protein RMS diet, while occludin did not differ among the 4 groups. Neither Gln nor Glu increased claudin-1 or occludin in rats fed 25% protein. CONCLUSIONS: These results suggest that neither Gln nor Glu supplementation can substitute effectively for whole protein in the developing rat small intestine for the outcomes that were evaluated.

Alkaline Phosphatase↗
PubMed2004

[Effect of Bugu Mixture on all-trans retinoic acid-induced apoptosis of bone marrow stromal cells].

OBJECTIVE: We used the SD rat's bone marrow stromal cells (BMSCs) cultured in vitro to observe the effects of Bugu Mixture on the apoptosis and to explore the molecular biologic mechanism of the treatment of osteoporosis with Bugu Mixture. METHODS: BMSCs were separated from the bones of the extremities of SD rats in vitro. The morphologic changes, the apoptosis cell cycles, the mitochondrion membrane potential changes, and the Bcl-2 and Bax gene expression were observed, and the effects of Bugu Mixture on the course of cell apoptosis were evaluated. RESULTS: The earlier use of Bugu Mixture could decrease the cells blocked in G0/G1 phase, and promote their synthesis of DNA in S phase. The expression of Bcl-2 was higher in the Bugu Mixture group than that in the all-trans retinoic acid (ATRA) induced group, and the expression of Bax was lower in the Bugu Mixture group than that in the ATRA induced group. The mitochondrion membrane potential descended significantly in the Bugu Mixture group than that in the ATRA induced group. CONCLUSION: The mechanism of the treatment of osteoporosis with Bugu Mixture is that the earlier use of Bugu Mixture can decrease the amount of apoptostic cells induced by ATRA, thus promoting the cell mitosis and restraining the apoptosis. It can also act as a protector to Bcl-2 located on the mitochondrion membrane. By preventing the transferring of the Bax protein from cell-plasma to mitochondrion membrane, it takes the advantage of Bcl-2 in forming Bcl-2/Bax homodimer so as to prevent the opening of the permeability transition pore to avoid the changing of mitochondrion membrane potential and the destruction of biosynthesis caused by the mitochondrion release of apoptosis inducing factors and to reach the objective of restraining apoptosis.

Animals↗
PubMed2004

[Preliminary study on the relationship between loads of human papillomavirus in cervical carcinoma and cervical intraepithelial neoplasia].

OBJECTIVE: To explore the relationship between loads of human papillomavirus in cervical carcinoma and cervical intraepithelial neoplasia. METHODS: From December 2001 to May 2002, 9075 married women aged from 35 to 50 years who lived in the areas with a high incidence of cervical carcinoma of Shanxi Province were screened high risk types of human papillomavirus (HPV) infection using hybrid capture II (HC-II). Of them, 2087 women with positive human papillomavirus further underwent colposcopy and multi-focal directed punch biopsies plus endocervical currettage. RESULTS: Two thousand and eighty-seven women were found with positive human papillomavirus infection, comprising 1402 (67.2%) women who were diagnosed as cervicitis, 663 (31.8%) women diagnosed as cervical intraepithelial neoplasia [including cervical intraepithelial neoplasia (CIN) I to III], and 22 (1.1%) women diagnosed as cervical squamous cell carcinoma (SCC). HPV-DNA loads of women with chronic and acute cervicitis were 150 +/- 11 and 108 +/- 13, respectively, with no significant difference between two groups statistically (P = 0.225). HPV-DNA loads for women with CIN I, CIN II and CIN III were 332 +/- 29, 358 +/- 35, and 370 +/- 31, respectively, all significantly higher than that of women with cervicitis (P = 0.000), but there were no significant differences among three groups (P > 0.05). HPV-DNA loads of women with cervical squamous cell carcinoma was 593 +/- 86, much higher than those of women with varied grades of cervical intraepithelial neoplasia and cervicitis (P < 0.05 and P < 0.01). CONCLUSIONS: The new technology using HC-II is an effective method to detect HPV infection in cervix. Viral loads of HPV-DNA increase with severity of cervical neoplasia. So it could be used for screening primary cervical carcinoma.

Adult↗
PubMed2004

[Endocervical curretage: an analysis of results in 1997 women].

OBJECTIVE: To study the value of endocervical curettage (ECC) in the detection of cervical intraepithelial neoplasia (CIN) and cervical cancer, and the necessity of ECC during colposcopic examination. METHODS: In the high prevalent area of cervical cancer in Shanxi Province, China, a total of 1997 women aged 35 approximately 45 years old were enrolled. Cervical cytology, colposcopy and targeted multiple biopsies, as well as ECC were performed for all women. RESULTS: Among the 1997 women received ECC, 31 was positive for abnormal histologic changes with a frequency of 1.6%. Of the 31 cases, 9 had low grade squamous intraepithelial lesions (LSIL, 0.5%), 20 had high grade squamous intraepithelial lesions (HSIL, 1.0%), and 2 had squamous-cell carcinoma. No pathologic diagnosis could be made in 131 women because the tissue curretaged was insufficient. The women with positive cytologic findings had higher frequency (5.3%) of abnormal ECC than those with negative cytologic findings (0.3%). There was positive correlation between the frequency of abnormal ECC and the grade of cytolologic findings. Abnormal ECC was present in 9.1% of those with unsatisfactory colposcopy while 1.3% of those with satisfactory colposcopy (P < 0.01). The frequency of abnormal ECC was 0.6% in patients with negative colpocopy, 0.9% in LSIL and 24.1% in HSIL. Frequency of abnormal ECC in women with a negative colposcopy or LSIL was significantly lower than that with HSIL. The positive rate of ECC pathologically verified was 3.3% in LSIL, 22.2% in HSIL and 50.0% in squamous carcinoma, respectively (P < 0.01). Of the 316 patients with positive cytology but negative colposcopy, ECC was abnormal in 8 (2.5%), of which HSIL cytologically verified was in 3. CONCLUSION: If cytology or colposcopy shows HSIL or more severe changes, and cytology is positive while colposcopy is unsatisfactory, ECC should be done routinely.

Adult↗
PubMed2004

Use of B-type natriuretic peptide in evaluation of early percutaneous coronary intervention in patients with acute coronary syndrome.

BACKGROUND: Previous studies showed that blood B-type natriuretic peptide (BNP) level could predict the prognosis of acute coronary syndromes (ACS). This study investigated the evaluation value of circulating BNP for early percutaneous coronary intervention (PCI) in patients with ACS. METHODS: Nine hundred and sixty consecutive patients with ACS were enrolled. Circulating BNP level was measured when each patient arrived at the emergency room. All patients underwent PCI in 90 minutes in spite of contraindication. Cardiac events (death from any cause, heart failure, and recurrence of acute myocardial infarction or ACS) were recorded during follow-up. RESULTS: In patients with BNP > or = 80 pg/ml, mortality from all causes within 1 month and 6 months in those underwent delayed PCI (> or = 6 hours) was significantly higher than those received early PCI (< 6 hours) (9.53% vs 3.49%, P = 0.027; 13.61% vs 5.24%, P = 0.010, respectively). Similarly, the incidence rate of heart failure in delayed PCI patients was significantly higher than those received early PCI within 1 month and 6 months (12.93% vs 4.66%, P = 0.008; 14.97% vs 6.98%, P = 0.021, respectively). The recurrence rate of acute myocardial infarction or ACS, however, was not significantly different between early PCI and delayed PCI patients in group BNP > or = 80 pg/ml. In patients with BNP < 80 pg/ml, no significant difference was observed between early PCI and delayed PCI patients with any of the above cardiac events within 1 month or 6 months. CONCLUSION: While early level of circulating BNP > or = 80 pg/ml, the incidence of mortality and heart failure, but not recurrence of acute myocardial infarction, is significantly reduced in patients with ACS provided by early PCI.

Adolescent↗
PubMed2004

[Side effects of glucocorticosteroids in the management of 1291 patients of SARS].

OBJECTIVE: To analysis the relationship between glucocorticosteroids (GCS) usage and side effects in the treatment of severe acute respiratory syndrome (SARS). METHODS: All clinical records of probable SARS patients in Beijing were collected and input into an Epi6 database, in which 1 291 patients had entire information and met the clinical criteria of SARS. The usage of GCS and GCS associated side effects were analyzed retrospectively. RESULTS: Patients accepted GCS therapy were 83.96% (n=1 084), whereas 16.04%(n=207) did not take GCS. The average dosage of GCS was 160 mg/d in the first week, and then reduced to 80 mg/d and 40 mg/d in the second and the third weeks, respectively. Initial blood glucose, systolic pressure (SBP), and diastolic pressure (DBP) were no significant difference between GCS group and non-GCS group. The highest blood glucose during the treatment in GCS group was markedly higher than that in non-GCS group [(8.68+/-4.80) mmol/L vs (6.39+/-3.71) mmol/L, P<0.05)]. The highest blood glucose and average blood glucose after initiation of GCS therapy were elevated in GCS group. The levels of blood glucose were correlated with the initial, maximum, and cumulative GCS dosages. Average blood glucose was increased markedly in groups with MP(Initial) > or =80 mg/d (Methyprednisonlone), MP(Maximal) > or =160 mg/d, or MP(Cumulative) > or = 3000 mg. The blood glucose grew up significantly in the first and the second weeks in the treatment with GCS, and then returned to normal level gradually. Hyperglycemia duration in the group with MP(Cumulative) > or =3000 mg persisted longer than that in the other groups (P< 0.05). The lowest serum potassium during the treatment and the duration of hypokalemia in GCS group were significantly different from that in non-GCS group [(3.66+/-0.50) mmol/L vs (4.01+/-0.51) mmol/L, P< 0.001 ;1(1, 75) days vs 1(1, 9) days, P<0.05, respectively]. Average serum potassium and the duration of hypokalemia were related to the dosages of GCS. Serum potassium reached its nadir in the first week of GCS treatment and then grew up in the second week. In groups with MP(Initial) > or =320 mg/d, MP(Maximal) > or =320 mg/d, and MP(Cumulative) > or =3000 mg, the level of serum potassium was lower and the duration of hypokalemia was longer than that in other groups. They began to returned to normal level in the third week. Administration of GCS prolonged the time of hypocalcemia[19 (1, 74) days in GCS group vs 8 (1, 32) days in non-GCS group, P< 0.05]. The duration of hypocalcemia was prolonged according to the increasing of the maximal or the cumulative dosage of GCS. However, the duration of hypocalcemia in group with MP(Cumulative) <999 mg was similar to that in non-GCS group (P > 0.05). After GCS administration, SBP and DBP were increased gradually, and reached their peaks in the fourth week [SBP(117.2+/-14.0) mm Hg and DBP (72.5+/-9.1) mm Hg vs SBP (120.0+/-12.5) mm Hg and DBP (74.5+/-8.7) mm Hg, P< 0.05, 1 mm Hg=0.133 kPa]. CONCLUSION: Hyperglycemia and hypokalemia are correlated with GCS dosage and duration. Administration with GCS influences SBP, DBP, and duration of hypocalcemia. Appropriate low dosage of GCS (MP(Initial) and MP(Maximal) < 159 mg/d, MP(Cumulative)< 2999 mg) causes few changes of blood glucose, serum potassium, and blood calcium. It is important to monitor laboratory findings during the treatment with GCS.

Dose-Response Relationship, Drug↗
PubMed2004

[The expression of matrix metalloproteinase-9 and tumor necrosis factor-alpha in cholesteatoma].

OBJECTIVE: To observe the expression of MMP-9, TNF-alpha in cholesteatoma and to determine their roles in the destruction of bone. METHOD: Immunohistochemical method (SP) and the computer image quantitative analysis were used to examine the expression of TNF-alpha, MMP-9 in 22 samples from cholesteatoma and 20 normal cases. At the same time, the correlation between the expressions of the two indexes and the erosion of ossicles were observed. RESULT: MMP-9 protein was only expressed in cholesteatoma stromal cells. TNF-alpha was expressed in both epithlium and stromal cells. The results of the computer image quantitative analysis showed that the mean optical density of MMP-9 and TNF-alpha in cholesteatoma were higher than that in normal skin epithelial tissue (P < 0.05), in addition, the two indexes were relative to the extent of ossicle destruction. CONCLUSION: MMP-9 and TNF-alpha are overexpressed in cholesteatoma and they are associated with ossicle destruction, which shows that MMP-9 and TNF-alpha are responsible for bone destruction in cholesteatoma; MMP-9 and TNF-alpha have a correlation in their expression, which suggest that the two factors act on each other possibly; Overexpression of MMP-9 is only observed in stromal cells and the immunostain of TNF-alpha also is observed in stromal cells which indicates that stromal cells play an important role in bone destruction.

Adolescent↗
PubMed2003

Cyclin L2, a novel RNA polymerase II-associated cyclin, is involved in pre-mRNA splicing and induces apoptosis of human hepatocellular carcinoma cells.

We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase II. The cyclin L2 protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase II and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis.

Amino Acid Sequence↗
PubMed2003

Water self-diffusion tensor changes in an avian genetic developmental model of epilepsy.

Diffusion tensor imaging (DTI) was used to investigate whether tissue anisotropy in the developing brain is modified by recurrent seizures in epileptic chickens. Twelve epileptic chickens were sorted equally into two experimental groups at 10 days old. Until the age of 180 days, one group was photically stimulated beginning at an age of 2 weeks and repeated every 2 days while the other group was not stimulated. The photic stimulation induced generalized tonic-clonic seizures, and the unstimulated group did not display seizures. Both treatment groups were imaged at three time points, 45 (juvenile), 90 (adolescent), and 180 (adult) days posthatching, and maps of major and minor elements of anisotropy (eta and epsilon), trace and fractional anisotropy (FA) were generated. The eta, epsilon, and trace values in the hyperstriatum, archistriatum, and optic tectum showed significant changes as a function of developmental time point. Differences and/or interactions due to seizures were seen in the archistriatum and optic tectum for eta, epsilon, and trace with the largest differences between the stimulated and unstimulated birds being seen for eta in juvenile birds in the archistriatum (38.1 x 10(-11) m(2)/s versus 18.0 x 10(-11) m(2)/s) and the optic tectum (53.9 x 10(-11) m(2)/s versus 27.1 x 10(-11) m(2)/s). With the DTI parameters being sensitive to microstructure in the brain, these results demonstrate that seizures produce measurable differences, over unstimulated chickens, in brain structure for juvenile chickens, but the differences disappear as the brain matures. In other words, while seizure activity appears to induce atypical biophysical change (relative to unseizing birds) in the brain at a young age, the change is apparently reversed as the brain matures.

Adaptation, Physiological↗
PubMed2003

Isomaltulose synthase (PalI) of Klebsiella sp. LX3. Crystal structure and implication of mechanism.

Isomaltulose synthase from Klebsiella sp. LX3 (PalI, EC 5.4.99.11) catalyzes the isomerization of sucrose to produce isomaltulose (alpha-D-glucosylpyranosyl-1,6-D-fructofuranose) and trehalulose (alpha-D-glucosylpyranosyl-1,1-d-fructofuranose). The PalI structure, solved at 2.2-A resolution with an R-factor of 19.4% and Rfree of 24.2%, consists of three domains: an N-terminal catalytic (beta/alpha)8 domain, a subdomain between N beta 3 and N alpha 3, and a C-terminal domain having seven beta-strands. The active site architecture of PalI is identical to that of other glycoside hydrolase family 13 members, suggesting a similar mechanism in substrate binding and hydrolysis. However, a unique RLDRD motif in the proximity of the active site has been identified and shown biochemically to be responsible for sucrose isomerization. A two-step reaction mechanism for hydrolysis and isomerization, which occurs in the same pocket is proposed based on both the structural and biochemical data. Selected C-terminal truncations have been shown to reduce and even abolish the enzyme activity, consistent with the predicted role of the C-terminal residues in the maintenance of enzyme conformation and active site topology.

Amino Acid Sequence↗