Biomedical subjects

Yi Ren

Publications and source records attributed to Yi Ren.

At least 37 records · Page 2Linked to original sources

PubMed2004

Modified Gaussian-2 level investigation of the identity ion-pair SN2 reactions of lithium halide and methyl halide with inversion and retention mechanisms.

Identity ion-pair S(N)2 reactions LiX + CH(3)X --> XCH(3) + LiX (X = F, Cl, Br, and I) have been investigated in the gas phase and in solution at the level of the modified Gaussian-2 theory. Two possible reaction mechanisms, inversion and retention, are discussed. The reaction barriers relative to the complexes for the inversion mechanism [DeltaH(cent) ( not equal )(inv)] are found to be much higher than the corresponding values for the gas phase anionic S(N)2 reactions, decreasing in the following order: F (263.6 kJ mol(-1)) > Cl (203.3 kJ mol(-1)) > Br (174.7 kJ mol(-1)) > I (150.7 kJ mol(-1)). The barrier gaps between the two mechanisms [DeltaH(cent) ( not equal ) (ret) - DeltaH(cent) ( not equal ) (inv)] increase in the order F (-62.7 kJ mol(-1)) < Cl (4.4 kJ mol(-1)) < Br (24.9 kJ mol(-1)) < I (45.1 kJ mol(-1)). Thus, the retention mechanism is energetically favorable for fluorine and the inversion mechanism is favored for other halogens, in contrast to the anionic S(N)2 reactions at carbon where the inversion reaction channel is much more favorable for all of the halogens. The stabilization energies for the dipole-dipole complexes CH(3)X. LiX (DeltaH(comp)) are found to be similar for the entire set of systems with X = F, Cl, Br, and I, ranging from 53.4 kJ mol(-1) for I up to 58.9 kJ mol(-1) for F. The polarizable continuum model (PCM) has been used to evaluate the direct solvent effects on the energetics of the anionic and ion-pair S(N)2 reactions. The energetic profiles are found to be still double-well shaped for most of the ion-pair S(N)2 reactions in the solution, but the potential profile for reaction LiI + CH(3)I is predicted to be unimodal in the protic solvent. Good correlations between central barriers [DeltaH(cent) ( not equal ) (inv)] with the geometric looseness of the inversion transition state %C-X( not equal ), the dissociation energies of the C-X bond (D(C-X)) and Li-X bond (D(Li-X)) are observed, respectively.

Journal Article↗

PubMed2004

The use of proteomics in the discovery of serum biomarkers from patients with severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a new infectious disease with a global impact. Understanding its pathogenesis and developing specific diagnostic methods for its early diagnosis are crucial for the effective management and control of this disease. By using proteomic technology, truncated forms of alpha(1)-antitrypsin (TF-alpha(1)-AT) were found to increase significantly and consistently in sera of SARS patients compared to control subjects. The result showed a sensitivity of 100% for SARS patients and a specificity of 92.8% for controls. Furthermore, the levels of these proteins significantly correlated with certain clinico-pathological parameters. The dramatic increase in TF-alpha(1)-AT may be the result of degradation of alpha(1)-AT. As alpha(1)-AT plays an important role in the protection of lung function, its degradation may be an important factor in the pathogenesis of SARS. These findings indicate that increased TF-alpha(1)-AT may be therapeutically relevant, and may also be a useful biological marker for the diagnosis of SARS.

Biomarkers↗

PubMed2004

A G2(+) level investigation of the gas-phase non-identity SN2 reactions of halides with halodimethylamine.

The gas-phase non-identity S(N)2 reactions on nitrogen Y(-) + NMe(2)X --> NMe(2)Y + X(-) (Y, X = F, Cl, Br, and I) were evaluated at the G2(+) level. The reactions are exothermic only when the nucleophile is the lighter halide. The complexation enthalpies for complexes Y(-) em leader Me(2)NX are found to correlate with electronegativity of X. Both central and overall barriers can be interpreted with the aid of Marcus equation. Kinetic and thermodynamic investigations predict that the nucleophilicity of X(-) decreases in the order: F(-) > Cl(-) > Br(-) > I(-) and the leaving-group ability increases in the order: F < Cl < Br < I.

Journal Article↗

PubMed2004

Propagation of gammaPKC translocation along the dendrites of Purkinje cell in gammaPKC-GFP transgenic mice.

To elucidate spatial and temporal profiles of the protein kinase C (PKC) activation in relation to neuronal functions including synaptic plasticity, we tried to detect PKC translocation in living brain slices. We first developed brain region-specific and inducible gammaPKC-GFP transgenic mice using a tetracycline (tet)-regulated system. In the transgenic mice, the expression of gammaPKC-GFP was region-specifically regulated by the promoter and abolished by the administration of doxycycline. Cerebellar slices from the mice were utilized for intracellular recording and fluorescence imaging of gammaPKC-GFP in Purkinje cells. GFP fluorescence was uniformly distributed from soma to dendritic arbor. When mGluR agonists were applied, the intensity was transiently increased at the edge of the dendrite and concomitantly decreased in the cytoplasm, indicating that gammaPKC translocated to the plasma membrane. This transient change in the pattern of GFP fluorescence simultaneously occurred throughout the Purkinje cell dendrites by agonist stimulation. Translocation of gammaPKC-GFP was also induced by electrical stimulation of parallel fibres. However, the event was not restricted at the distal dendrites, propagated forwardly along the dendritic tree and reached to the proximal trunk close to the soma. Time course of the propagation was slower than the electrical signal and Ca(2+) waves and faster than conveying molecules through microtubules. The present results indicate that PKC signals activated locally by parallel fibre input could propagate to the soma through dendrites in living Purkinje neurones. The findings may provide us with a new insight for understanding molecular mechanisms of the synaptic plasticity including cerebellar long-term depression.

Animals↗

PubMed2004

Synthesis of the heteropolysaccharide O antigen of Escherichia coli O52 requires an ABC transporter: structural and genetic evidence.

The structural and genetic organization of the Escherichia coli O52 O antigen was studied. As identified by sugar and methylation analysis and nuclear magnetic resonance spectroscopy, the O antigen of E. coli O52 has a partially O-acetylated disaccharide repeating unit (O unit) containing D-fucofuranose and 6-deoxy-D-manno-heptopyranose, as well as a minor 6-deoxy-3-O-methylhexose (most likely, 3-O-methylfucose). The O-antigen gene cluster of E. coli O52, which is located between the galF and gnd genes, was found to contain putative genes for the synthesis of the O-antigen constituents, sugar transferase genes, and ABC-2 transporter genes. Further analysis confirmed that O52 employs an ATP-binding cassette (ABC) transporter-dependent pathway for translocation and polymerization of the O unit. This is the first report of an ABC transporter being involved in translocation of a heteropolysaccharide O antigen in E. coli. Genes specific for E. coli O52 were also identified.

ATP-Binding Cassette Transporters↗

PubMed2004

Macrophage migration inhibitory factor enhances neoplastic cell invasion by inducing the expression of matrix metalloproteinase 9 and interleukin-8 in nasopharyngeal carcinoma cell lines.

BACKGROUND: Nasopharyngeal carcinoma (NPC) shows highly invasive and metastatic features. This study aims to investigate macrophage migration inhibitory factor (MIF)-induced invasion of NPC cells in vitro and the effects on matrix metalloproteinases (MMPs) and interleukin-8 (IL-8), and to study the mechanism of tumor cell invasion and metastasis in the early stage of NPC. METHODS: Two nasopharyngeal carcinoma cell lines, CNE-1 and CNE-2, were adopted in this study. The NPC cell invasion and migration were evaluated by microinvasion assay. The variation of expression percentages of MMP2- or MMP9-positive cells was detected by flow cytometry in two cell lines with or without MIF treatment. Western blotting and RT-PCR were used to assay the protein and mRNA expressions of MMP2 and MMP9. The IL-8 concentration secreted by NPC cells was compared with the cells with different treatments using ELISA. RESULTS: After treating with MIF for 48 hours, the cell numbers of CNE-1 and CNE-2 which went through the 8-microm filter membrane were increased. Compared with non-MIF treated NPC cells, significant difference could be found both in CNE-1 (P = 0.005) and CNE-2 cells (P = 0.001). The percentages of MMP9-positive cells were significantly increased in both CNE-1 [from (28.5 +/- 2.5)% to (82.4 +/- 3.5)%, P = 0.001] and CNE-2 [from (32.8 +/- 3.5)% to (86.1 +/- 1.6)%, P = 0.002]. The relative intensity of MMP9 protein expression was also enhanced in both cell lines (CNE-1: from 83.1 +/- 6.0 to 242.9 +/- 22.9, P = 0.002; CNE-2: from 84.4 +/- 4.3 to 278.9 +/- 29.7, P = 0.003). Correspondingly, the increased MMP9 mRNA expression level was significantly detectable in both cell lines. The concentration of IL-8 in the supernatant of CNE-2 was higher [(1201.8 +/- 593.3) pg/ml] after treatment. It was also remarkably higher than that in the supernatant of CNE-2 without treatment (P = 0.026). However, there was no significant difference in the concentration variation of IL-8 in CNE-1 (P = 0.581), while the IL-8 mRNA level was only enhanced in CNE-2. CONCLUSIONS: MIF can induce potent invasion of NPC cell lines in vitro, and the infiltrating lymphocytes in NPC might be responsible for the invasion and metastasis of tumor cells. MIF cytokine which is secreted by these infiltrating lymphocytes might contribute to the invasion as well as metastasis of NPC in the early stages by induction of MMP9 and IL-8 in an indirect pathway.

Blotting, Western↗

PubMed2004

Association of E-cadherin and beta-catenin with metastasis in nasopharyngeal carcinoma.

BACKGROUND: This study was designed to detect methylation of E-cadherin gene promoter and gene mutation of beta-catenin in exon 3 and their expression of protein and mRNA in primary tumor and lymph node metastatic tumor of nasopharyngeal carcinoma (NPC), and investigate the mechanism of invasion and metastasis of neoplastic cells in NPC. METHODS: Fourty-two fresh biopsy samples were taken from untreated NPC patients at the Affiliated Hospital of Sun Yat-sen Medical College, Sun Yat-sen University, Guangzhou, China during the period of 1999-2002. Among them 21 were taken from primary tumors and the other 21 from lymph node metastatic tumors. The gene promoter methylation of E-cadherin was detected by methylation-specific PCR (MSP). The mutation in exon 3 of beta-catenin was detected by direct sequencing analysis. RT-PCR, Western blot and immunohistochemical staining were used to detect the mRNA and protein expression patterns in both primary and metastatic tumors of NPC. RESULTS: Down-regulated expression of E-cadherin in metastatic tumor was compared with that in primary tumor. Reduced expression of E-cadherin was found to be correlated with lymph node metastatic tumor of NPC (P = 0.004); but there was no obvious correlation between primary and metastatic tumors in the expression of beta-catenin (P = 0.698). The mRNA expression level of E-cadherin in metastatic tumors decreased significantly compared with that in primary tumors. However, little change was observed in the mRNA level of beta-catenin in different tumor tissues. Only 4 samples (19.1%) displayed gene promoter methylation of E-cadherin in primary tumor and 10 samples (47.6%) showed methylated form of E-cadherin. The gene promoter methylation of E-cadherin was more common in metastatic tumor than in primary tumor of NPC (P = 0.024). Only 2 (4.76%) of the 42 samples showed mutations in exon 3 of beta-catenin at 41 (T41A, ACC-->GCC) and codon 47 (S47T, AGT-->ACT). The cytoplasmic and nuclear expression of beta-catenin in tumor was not found in any samples of NPC. CONCLUSIONS: The results suggest that the downregulation of E-cadherin results from the gene promoter aberrant methylation of E-cadherin and that the methylation of E-cadherin plays an important role in invasion and metastasis of tumor cells in NPC. However, beta-catenin mutation is an infrequent event in NPC, and beta-catenin is not a critical factor influencing the invasion and metastasis of tumor cells in NPC.

Adult↗

PubMed2003

Interleukin-8 serum levels in patients with hepatocellular carcinoma: correlations with clinicopathological features and prognosis.

PURPOSE: In this study, we measured the serum interleukin-8 (IL-8) levels in patients with hepatocellular carcinoma (HCC) to evaluate its correlation with clinicopathological features and prognosis. EXPERIMENTAL DESIGN: ELISA was used to detect the concentrations of IL-8, vascular endothelial growth factor, and macrophage migration inhibitory factor in preoperative sera of 59 patients with resection of HCC and 15 healthy subjects. RESULTS: Preoperative serum IL-8 was found to be significantly elevated in patients with HCC compared with healthy subjects (median, 17.6 versus 1.0 pg/ml, P=0.046). The levels of IL-8 correlated significantly with a large tumor size (>5 cm), absence of tumor capsule, presence of venous invasion, and advanced pathological tumor-node-metastasis stage. Serum IL-8 level was a significant prognostic factor in terms of disease-free and overall survival. Patients with a serum IL-8 level of >17.6 pg/ml had a poorer disease-free survival than those with a level of <17.6 pg/ml (median disease-free survival 4.7 versus 19.2 months). Multivariate analyses showed that serum IL-8 level was a significant and independent prognostic factor of survival. CONCLUSIONS: Significant correlations of serum IL-8 levels with tumor size and tumor stage suggest that IL-8 may be directly or indirectly involved in the progression of HCC. These findings indicate that serum IL-8 may be a useful biological marker of tumor invasiveness and an independent prognostic factor for patients with HCC.

Adolescent↗

PubMed2003

A reverse turn structure induced by a D,L-alpha-aminoxy acid dimer.

Our previous work revealed that two adjacent D-alpha-aminoxy acids could form two homochiral N-O turns, with the backbone folding into an extended helical structure (1.8(8)-helix). Here, we report the conformational studies of linear peptides 3-6, which contain a D,L-alpha-aminoxy acid dimer segment. The NMR and X-ray analysis of 3 showed that it folded into a loop conformation with two heterochiral N-O turns. This loop segment can be used to constrain tetrapeptides 4 and 6 to form a reverse turn structure. (1)H NMR dilution studies, DMSO-d6 addition studies, and 2D-NOESY data indicated that tetrapeptides 4 and 6 folded into reverse turn conformations featured by a head-to-tail 16-membered-ring intramolecular hydrogen bond. In contrast, tetrapeptide 5 with L-Ala instead of Gly or D-Ala as the N-terminal amino acid could not form the desired reverse turn structure for steric reasons. Quantum mechanics calculations showed that model pentamide 7, with the same substitution pattern of 4, adopted a novel reverse turn conformation featuring two heterochiral N-O turns (each of an 8-membered ring hydrogen bond), a cross-strand 16-membered ring hydrogen bond, and a 7-membered ring gamma-turn.

Amino Acids↗

PubMed2003

Macrophage migration inhibitory factor: roles in regulating tumor cell migration and expression of angiogenic factors in hepatocellular carcinoma.

Macrophage migration inhibitory factor (MIF) may contribute to multiple aspects of tumor progression, including control of cell proliferation, differentiation, cell survival and angiogenesis. However, the potential roles of MIF in regulating hepatocellular carcinoma (HCC) tumor cell migration and the expression of angiogenic factors by HCC tumor cells have not been studied yet. In our study, we reported that intracellular MIF mRNA and protein were overexpressed in HCC tissues compared to nontumor tissues by using in situ hybridization and immunohistochemic staining. HCC tumor cell lines also secreted large amounts of MIF into the supernatants of tumor cell culture. To assess the role of MIF in HCC, we employed the transwell invasion chamber to study the effect of MIF on tumor cell migration. Our results showed that recombinant MIF and the supernatants of tumor cell line culture could enhance the invasion and migration of HCC cells. This effect can be inhibited by the addition of a neutralizing anti-MIF antibody. We observed that increased MIF serum levels correlated with higher levels of interleukin-8 (IL-8) in the sera of patients with HCC than in normal volunteers. We therefore hypothesized that MIF may regulate the production of angiogenic factors by HCC cells. To test this hypothesis, we examined the effect of MIF treatment on vascular endothelial growth factor (VEGF) and IL-8 expression by HCC cell lines. MIF induced a significant dose-dependent increase in IL-8 and VEGF production. Taken together, our results indicated that MIF may act as an autocrine-acting factor that stimulates angiogenesis and metastasis in HCC by promoting expression of angiogenic factors and migration of tumor cells. A more detailed understanding of the MIF regulatory mechanisms involved may provide insight into new direction in the treatment of HCC.

Adult↗

PubMed2003

Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus.

OBJECTIVE: To evaluate whether patients with systemic lupus erythematosus (SLE) have a higher rate of apoptosis in and secondary necrosis of polymorphonuclear neutrophils (PMNs) and macrophages compared with controls; to compare the rate of macrophage phagocytic clearance of apoptotic PMNs in patients with SLE and healthy controls; to evaluate whether in vitro PMN and macrophage apoptosis and secondary necrosis, and the ability of macrophages to phagocytose apoptotic bodies, are correlated with lupus disease activity; and to determine whether macrophage clearance of apoptotic bodies in patients with SLE and normal controls is related to certain serum factors. METHODS: Thirty-six patients with SLE and 18 healthy, nonsmoking volunteers were studied. PMNs and monocytes were isolated from fresh blood and cultured in the presence of different sources of serum. Apoptotic PMNs and macrophages were examined by annexin V binding and morphology on May-Giemsa-stained cytopreparations, at different time points. The presence of secondary necrotic PMNs and macrophages was verified by staining with trypan blue. Macrophage phagocytosis of apoptotic PMNs was measured using a coded, observer-blinded, microscopically quantified phagocytosis assay. Cells were cultured in the presence of serum obtained from healthy subjects or from patients with SLE. RESULTS: At 5 and 24 hours, the percentage of apoptotic PMNs from patients with SLE was significantly higher than that of PMNs from healthy subjects. At 24 and 48 hours, the percentage of secondary necrotic PMNs from patients with SLE was also significantly higher than the percentage of necrotic PMNs from controls. Serum from patients with SLE accelerated the rate of apoptosis in and secondary necrosis of PMNs from healthy subjects. Macrophages from SLE patients were less capable of phagocytosing apoptotic PMNs compared with macrophages obtained from controls. Macrophages from patients with active SLE were less capable of phagocytosing apoptotic PMNs than were macrophages from patients with inactive SLE, but the difference was not statistically significant. The percentage of phagocytosis of apoptotic PMNs by macrophages from SLE patients correlated negatively with the SLE Disease Activity Index, serum levels of anti-double-stranded DNA, and the erythrocyte sedimentation rate, and correlated positively with serum levels of C3, C4, and albumin, the hemoglobin level, and the leukocyte count. Serum from SLE patients not only significantly increased macrophage apoptosis in cells from healthy subjects but also remarkably down-regulated the clearance of apoptotic PMNs by macrophages from healthy subjects. In contrast, serum from healthy subjects significantly increased phagocytosis of apoptotic PMNs by macrophages from SLE patients. CONCLUSION: The observed increase of apoptotic PMNs and macrophages and the poor ability of macrophages from patients with SLE to phagocytose apoptotic bodies may indicate an impaired clearance mechanism, which may be mediated by factors in a patient's serum.

Adolescent↗

PubMed2003

Investigation on biovars and genotypes of Ureaplasma urealyticum in the cervix in a Chinese gynecologic check-up population and sex workers.

Ureaplasma urealyticum is a causative agent of non-gonococcal urethritis and is implicated in the pathogenesis of several other diseases. However, U. urealyticum is also frequently found in the normal genitourinary tract. To characterize the distribution pattern of biovars and genotypes in normal physical check-up women and in sex workers, cervical swabs taken from 261 physical check-up clients and 98 sex workers were cultured. Positive cultures were further biotyped and genotyped by PCR. The data indicate that a) U. urealyticum is more frequently isolated in sex workers than in physical check-up women (p < 0.001); b) infection with only one genotype (genotype 1, 3 or 6) of biovar 1 is frequently found in physical check-up women; c) biovar 2 infection and mixed infection caused by more than one genotype of biovar 1 are more prevalent in sex workers than in physical check-up women (p < 0.001 and p < 0.01, respectively); d) no difference in distribution of genotype 1, 3 and 6 of biovar 1 is found between sex workers and physical check-up women (p = 0.396); e) the PCR method described here is relatively simple, rapid and specific for the biotyping between biovar 1 and 2 and genotyping of genotypes 1, 3, 6, and 14 in biovar 1.

Adult↗

PubMed2003

[Detection of SARS-CoV RNA in stool samples of SARS patients by nest RT-PCR and its clinical value].

OBJECTIVE: To investigate of severe acute respiratory syndrome (SARS) convalescent stool shedding by RT-PCR. METHODS: One hundred and three stool samples from 46 SARS patients were collected on May 16th, 20th, and 23rd, 2003. For each sample, RNA was extracted using commercial kit and 7 Nest RT-PCR using a 14-pair different SARS-associated coronavirus (SARS-CoV) special primers were carried out simultaneously. RESULTS: Among these 46 SARS patients, 17 cases (37.0%) were stool SARS-CoV RT-PCR negative, and 29 cases (63.0%) were SARS-CoV RT-PCR positive. The duration of positive cases lasted (31.76 +/- 10.78) d (12-64 d). The longest stool shedding case in this study lasted 64 days. Two serial stool samples and for each sample 2 RT-PCR tests using different primers were positive in this case. CONCLUSIONS: Our study observed longest stool shedding of SARS patients to be 64 days after initial onset of SARS. The average stool shedding was 32 days. Hence it is important to think highly of SARS convalescent patient stool sterilization.

Adolescent↗

PubMed2003

[Antitumor effect of gene therapy with recombinant adenovirus-mediated human interleukin-2 gene transfer and its mechanism].

OBJECTIVE: To explore the transfection, expression, antitumor effect and mechanism of a replication-deficient adenovirus vector expressing human IL-2 gene (advhIL-2) in a murine H22 hepatocellular carcinoma model. METHODS: KM mice bearing tumor 100-200 mm3 were injected intratumorally with advhIL-2, adv-LacZ or with PBS alone. The tumor evolution was recorded every 3 days. The transfection and expression of the recombinant adenovirus were examined with X-gal staining and RT-PCR respectively. The splenic LAK and CTL activities were assayed with 51Cr 4 hours release. The infiltration of CD4+ and CD8+ T cells in the tumors were analyzed with immunofluorescence. RESULTS: It was found that the recombinant adenovirus can bring about in vivo effective transfection and expression. The continuosly expressive time of advhIL-2 is longer than 12 days. AdvhIL-2 has dose-dependent anti-tumor effect. The mice received a dose of 2 x 10(9) pfu advhIL-2 divided into halves for two injections developed tumor more slowly and survived much longer than the mice treated with PBS (P < 0.01). Moreover, advhIL-2 increased the splenic LAK and CTL activities, CD4+ and CD8+ T cell infiltration in the H22 tumors significantly. CONCLUSION: Adenovirus-mediated hIL-2 gene treatment has significant antitumor activity in pre-established hepatocellular carcinoma in mice. Antitumor immunity might be responsible for the therapeutic effect.

Adenoviridae↗

PubMed2002

Immunization with Epstein-Barr Virus (EBV) peptide-pulsed dendritic cells induces functional CD8+ T-cell immunity and may lead to tumor regression in patients with EBV-positive nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC), a common neoplasm in Southeast Asia, is EBV-positive and expresses a limited number of antigens, including latent membrane protein 2. In this study, autologous monocyte-derived dendritic cells were cultured from patients with advanced NPC, matured with cytokine, pulsed with HLA-A1101-, A2402-, or B40011-restricted epitope peptides from EBV latent membrane protein 2 and injected into inguinal lymph nodes. Sixteen patients with local recurrence or distant metastasis after conventional therapies received four injections at weekly intervals. Epitope-specific CD8+ T-cell responses were elicited or boosted in 9 patients receiving HLA-A1101- or A2402-restricted peptides, with stronger responses seen to the A1101 peptide. Furthermore, epitope-specific cytotoxicity was detectable in peripheral blood T cells harvested at 3-months after vaccination from A1101-responsive patients, and in 2 patients, this coincided with partial tumor reduction. Approaches leading to stronger and more sustained EBV-specific T-cell responses, therefore, may have therapeutic potential in the context of NPC.

Adult↗

PubMed2002

Cyclic hexapeptide of D,L-alpha-aminoxy acids as a selective receptor for chloride ion.

Cyclic hexapeptide 2, prepared from linear hexapeptide 1 of alternating d- and l-alpha-aminoxy acids, was found to adopt a C3 symmetric and bracelet-like conformation with consecutive eight-membered-ring hydrogen bonds (N-O turns) in nonpolar solvents, similar to that of valinomycin, a cyclodepsipeptide that binds cations selectively. However, 2 showed affinities for halide ions with selectivity following the order of Cl- > F- > Br-. The observed higher selectivity for Cl- (Ka = 11880 M-1) over F- (Ka = 30 M-1) in CD2Cl2 suggested that the selectivity of 2 for halide ions is mainly governed by the size complementarity rather than the hydrogen-bonding strength. Upon Cl- ion binding, the original bracelet-like conformation of 2 turned into a rather flat conformation with all six amide NHs pointing inward to form hydrogen bonds with Cl-.

Amino Acids↗

PubMed2002

Inhibition of osteoclastogenesis by the secretion of osteoprotegerin in vitro by rat dental follicle cells and its implications for tooth eruption.

Tooth eruption requires the presence of the dental follicle, a loose connective tissue sac that surrounds each unerupted tooth. Early postnatally in the rat, the follicle secretes colony-stimulating factor-1 (CSF-1) and monocyte chemotactic protein-1 (MCP-1), chemotactic molecules that are probably responsible for the recruitment of mononuclear cells. These cells, in turn, fuse to form osteoclasts, which are required for alveolar bone resorption to form an eruption pathway. Recent studies have shown that the osteoprotegerin (OPG) gene is expressed in the dental follicle, but in the first mandibular molar of the rat, that expression is reduced at day 3, the time of maximal osteoclast numbers on the alveolar bone. Inhibition of OPG expression at this time would allow osteoclast formation/activation. To determine if the dental follicle cells do secrete OPG that inhibits osteoclastogenesis, spleen cell cultures were established and soluble osteoclast differentiation factor (ODF) and CSF-1 added to some of them to promote osteoclast formation. In other cultures, dental follicle cells were added in an insert, such that they did not touch the spleen cells. Using a quantitative, tartrate-resistant acid phosphatase (TRAP) assay, it was shown that ODF and CSF-1 promoted osteoclastogenesis in the spleen cell cultures, but the addition of the follicle cells inhibited this and returned the TRAP activities to those seen in cultures of spleen cells only. Adding anti-OPG to these cultures, however, negated the effect of the follicle cells, demonstrating that OPG was the inhibitory molecule secreted by those cells. The follicle cells also immunostained for OPG, confirming that they synthesize OPG. These findings, coupled with those of other studies which show that the periodontal ligament (a derivative of the dental follicle) also secretes OPG, indicate that, except for the period of time in tooth eruption, where osteoclast formation is needed to form an eruption pathway, secretion of OPG would be the norm, presumably to prevent resorption of alveolar bone and subsequent disruption of the periodontal ligament.

Acid Phosphatase↗

PubMed2002

Effects of partial ischaemia and volume loading on myocardial efficiency and cardiac performance in dogs.

AIMS AND METHODS: To determine whether volume loading may be beneficial for the performance of ischaemic heart, myocardial ischaemia was created by partial occlusion of the left anterior descending coronary artery (LAD) to reduce the blood flow to 30 approximately 40% of basal level in 11 open chest anaesthetised dogs. Global left ventricular function as well as regional performance were studied under four different levels of volume loading, euvolemia (EUVO), hypervolemia (HYPER), normovolemia and hypovolemia. RESULTS: Left ventricular dP/dt(max) and cardiac output were decreased significantly during partial occlusion (3511.2+/-425.2 mmHg/s and 0.9+/-0.1 l/min) compared with pre-occlusion (4486.5+/-419.2 mmHg/s and 1.3+/-0.1 l/min) (P<0.05). Cardiac work was also lowered during partial occlusion (75.4+/-5.2 vs. 106.5+/-2.4 mmHgxl/min) (P<0.05). During volume loading, cardiac output and work were elevated (1.2+/-0.2 l/min and 94.0+/-5.4 mmHgxl/min) compared with EUVO (P<0.05). Local contractile dysfunction occurred in the LAD region after partial occlusion. There were no significant differences of dysfunction between any conditions of volume loading. Percentage shortening of the LAD region was decreased during partial occlusion (8.3+/-1.1 vs. 25.0+/-2.7%) and also was higher in HYPER (13.5+/-2.6%) than that in EUVO (P<0.05). Partial occlusion and different conditions of volume loading did not significantly change the force and local work in the LAD region. Myocardial O(2) consumption (MVO(2)) in LAD region was decreased during partial occlusion with different levels of volume loading (P<0.05). Local myocardial efficiency (work/MVO(2)) was increased during partial occlusion compared with pre-occlusion (941.3+/-56.2 vs. 551.0+/-65.5 gxmm/ml O(2)/min/100 g, P<0.05) and was also higher in HYPER (1208.6+/-48.4 gxmm/ml O(2)/min/100 g) than that in EUVO (P<0.05). Local systolic work was decreased during partial occlusion compared with pre-occlusion (9.5+/-1.5 vs. 14.2+/-1.3 gxmm/beat), whereas local myocardial systolic mechanical efficiency was increased (496.3+/-45.7 vs. 667.2+/-39.8 gxmm/ml O(2)/min/100 g). There were no significant changes of local systolic work and local systolic myocardial efficiency between different volume loading, although they tend to be elevated with increasing volume loading. CONCLUSION: Increase of blood volume by 15% improved the impaired global performance caused by partial occlusion of the LAD in open-chest dogs. This improvement was not accompanied by further dysfunction or increased MVO(2) of ischaemic myocardium, and therefore might be beneficial without causing further damage to the insulted myocytes.

Analysis of Variance↗