Biomedical subjects

L Chen

Publications and source records attributed to L Chen.

At least 811 records · Page 45Linked to original sources

PubMed1997

Preservation of endogenous antioxidant activity and inhibition of lipid peroxidation as common mechanisms of antiatherosclerotic effects of vitamin E, lovastatin and amlodipine.

OBJECTIVES: We sought to document the common mechanisms of the antiatherogenic effects of the cholesterol-lowering hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin, the dihydropyridine Ca2+ blocker amlodipine and the antioxidant vitamin E. BACKGROUND: Vitamin E, HMG-CoA reductase inhibitors and Ca2+ blockers each inhibit atherosclerosis in hypercholesterolemic animals. METHODS: New Zealand White rabbits were fed regular chow (Group A), chow with 1% cholesterol (Group B), 1% cholesterol diet plus lovastatin (Group C), 1% cholesterol diet plus vitamin E (Group D) or 1% cholesterol diet plus amlodipine (Group E) for 12 weeks. The extent of aortic atherosclerosis was measured by planimetry of the sudanophilic area. Malondialdehyde (MDA) and superoxide dismutase (SOD) in blood were measured as indexes of lipid peroxidation and antioxidant activity, respectively. RESULTS: Group A rabbits showed no atherosclerosis, whereas Group B rabbits had 17.4 +/- 9.3% (mean +/- SD) of the aorta covered with atherosclerosis, and Groups C, D and E rabbits had significantly less atherosclerosis. Plasma SOD activity was lower in Group B than in Group A (6.9 +/- 1.1 vs. 12.8 +/- 1.5 U/ml, p < 0.01) and was preserved in the groups given lovastatin, vitamin E or amlodipine with a high cholesterol diet. The serum MDA level was higher in Group B rabbits than Group A rabbits (12.1 +/- 2.6 vs. 1.2 +/- 0.1 nmol/ml, p < 0.01) and increased minimally in rabbits given lovastatin, vitamin E or amlodipine with a high cholesterol diet. In in vitro experiments, both lovastatin and amlodipine preserved SOD activity and reduced the oxidizability of low density lipoproteins by rabbit leukocytes. CONCLUSIONS: This study suggests that a reduction in lipid peroxidation and preservation of SOD may be common mechanisms of antiatherosclerotic effects of lovastatin, vitamin E and amlodipine.

Amlodipine↗

PubMed1997

Osteopontin is associated with bioprosthetic heart valve calcification in humans.

Calcification of non-osseous tissues such as heart valves or vessels is a major concern in clinical practice. The exact mechanism is still unknown. Numerous studies have shown that mineral deposits of crystalline hydroxyapatite within these tissues were associated with increased non-collagenous protein content. More recently osteopontin was found to be associated with calcification in living tissues such as vessels and native human aortic valves. The aim of this study was to determine whether or not non-collagenous proteins can also be found in non-living tissues such as glutaraldehyde-pretreated porcine valves after implantation in humans. Thirty-eight glutaraldehyde pretreated porcine bioprostheses were studied: 16 not implanted and 22 after 11 years of implantation in the aortic and mitral valve position in humans. In areas of calcification vizualized by Von Kossa staining and microradiography, immunostaining using polyclonal antibodies against calcium-binding proteins showed osteopontin positive staining and no staining for osteocalcin, bone sialoprotein or osteonectin. In uncalcified areas and in non-implanted values, staining for osteopontin or other calcium-binding proteins was negative. Western blot analysis of macroscopically calcified and uncalcified areas showed that several proteins were adsorbed in implanted values and confirmed the presence of osteopontin in the calcified areas, while no immunolabelling was found in non-calcified areas, in uncalcified valves and in non-implanted valves. Thus the presence of osteopontin in the calcified areas of bioprosthetic heart valves implanted in human indicates that this protein is associated with bioprosthetic valvular calcification. Since these values are made of non-living connective tissue, and no cell immunostained for osteopontin was found around the calcified area, this suggests that a non-cellular mediated mechanism involving protein adsorption may play a role in bioprosthetic valvular calcification.

Bioprosthesis↗

PubMed1997

Pathophysiology of portal hypertension.

Portal hypertension is a common clinical syndrome associated with chronic liver diseases and is characterized by a pathological increase in portal pressure. Increase in portal pressure is because of an increase in vascular resistance and an elevated portal blood flow. The site of increased intrahepatic resistance is variable and is dependent on the disease process. The site of obstruction may be: pre-hepatic, hepatic, and/or post-hepatic. In addition, part of the increased intrahepatic resistance is because of increased vascular tone. Another important factor contributing to increased portal pressure is elevated blood flow. Peripheral vasodilatation initiates the classical profile of decreased systemic resistance, expanded plasma volume, elevated splanchnic blood flow and elevated cardiac index. The elevated portal pressure leads to formation of portosystemic collaterals and oesophageal varices. Pharmacotherapy for portal hypertension is aimed at reducing both intrahepatic vascular tone and elevated splanchnic blood flow.

Esophageal and Gastric Varices↗

PubMed1997

Potent inhibition of protein-tyrosine phosphatase by phosphotyrosine-mimic containing cyclic peptides.

In an effort to derive potent and bioavailable protein-tyrosine phosphatase inhibitors, we have previously reported hexameric peptides based on the epidermal growth factor receptor sequence EGFR988-993 (Asp-Ala-Asp-Glu-Xxx-Leu, where Xxx = Tyr), in which the tyrosyl residue has been replaced by the non-hydrolyzable phosphotyrosyl mimics phosphonomethylphenylalanine (Pmp), difluorophosphonomethylphenylalanine (F2Pmp) and O-malonyltyrosine (OMT). Inhibitory potencies (IC50 values) of these peptides against the tyrosine phosphatase PTP IB were 200, 0.2 and 10 microM, respectively. Since cellular penetration of peptides containing highly charged phosphonate residues is compromised, and good bioreversible protection strategies for the F2Pmp residue have not yet been reported, the OMT residue is of particular interest in that it affords potential new prodrug approaches. In the current study we have prepared cyclized versions of the OMT-containing EGFR988-993 peptide in order to increase its proteolytic stability and restrain conformational flexibility. Three different cyclic analogues were synthesized. Two of these were cyclized through the peptide backbone ('head to tail') using in one case a single glycine spacer (heptamer peptide) and in the second instance, two glycines (octamer peptide). In a PTPI-based assay the cyclic heptamer experienced a two-fold loss of potency (Ki = 25.2 +/- 3.9 microM) relative to the linear hexamer parent (Ki = 13 +/- 0.9 microM), while the cyclic octamer demonstrated a live-fold increase in potency (Ki = 2.60 +/- 0.11 microM). The third peptide was cyclized by means of a sulfide bridge between the side chain of a C-terminally added cysteine residue and the beta-carbon of a N-terminal acetyl residue. Although the overall size of this ring was identical to that exhibited by the preceding backbone-cyclized octamer, it displayed a three-fold enhancement in potency (Ki = 0.73 +/- 0.03 microM). The structural basis for the observed results are discussed. Conformation restrictions induced by cyclization could aid in defining geometries for peptidomimetic design. Finally, it can be speculated that cyclization of other liner PTP-inhibitory peptides, such as the F2Pmp-containing hexamer, may also increase their potency.

Biological Availability↗

PubMed1997

Pathophysiology of portal hypertension.

Portal hypertension is a common clinical syndrome associated with chronic liver diseases, and is characterized by a pathological increase in portal pressure that leads to the formation of portosystemic collaterals resulting in shunting of portal blood into the systemic circulation. The increase in portal pressure is due to an increase in vascular resistance and an elevated portal blood flow. The site of increased resistance is variable, and dependent upon the disease process. The site of relative obstruction may be prehepatic, hepatic, or posthepatic. There are several intrahepatic lesions that lead to increased resistance. Some of these lesions are irreversible, like fibrosis, regenerating nodules, and capillarization of the space of Disse; however, there is a functional component, increased vascular tone, which contributes to increased intrahepatic resistance and is potentially reversible. Another important factor contributing to the increased portal pressure is elevated portal blood flow. Peripheral vasodilatation initiates the classical profile of decreased systemic resistance, expanded plasma volume, elevated splanchnic blood flow, and elevated cardiac index, which characterize the hyperdynamic circulatory state. This hyperdynamic circulation is responsible for various complications of portal hypertension.

Collateral Circulation↗

PubMed1997

Synthesis of depurinating DNA adducts formed by one-electron oxidation of 7H-dibenzo[c,g]carbazole and identification of these adducts after activation with rat liver microsomes.

It is hypothesized that 7H-dibenzo[c,g]carbazole (DBC) is metabolically activated by one-electron oxidation in accordance with its propensity to be easily oxidized to its radical cation. Iodine oxidation of DBC produces a radical cation that subsequently binds to nucleophilic groups of dG or Ade. Oxidation of DBC in the presence of dG products three adducts: DBC-5-N7Gua, DBC-6-N7Gua, and DBC-6-C8Gua, whereas in the presence of Ade, four adducts are obtained: DBC-5-N7Ade, DBC-5-N3Ade, DBC-5-N1Ade, and DBC-6-N3Ade. Formation of these adducts demonstrates that the DBC radical cation reacts at C-5 or C-6 with the reactive nucleophiles N-7 and C-8 of dG and N-7, N-3, and N-1 of Ade. Formation DNA adducts by DBC was studied by using horesradish peroxidase or 3-methylcholanthrene-induced rat liver microsomes for activation. Identification of the biologically-formed depurinating adducts was achieved by comparison of their retention times on HPLC in two different solvent systems and by matrix-assisted laser desorption ionization (MALDI) mass spectrometry. Quantitation of the adducts formed by rat liver microsomes shows that 96% are depurinating adducts, DBC-5-N7Gua (11%), DBC-6-N7Gua (32%), and DBC-5-N7Ade (53%), and 4% are unidentified stable adducts. Activation of DBC by horseradish peroxidase affords 32% stable unidentified adducts and 68% depurinating adducts: 19% DBC-5-N7Gua, 13% DBC-6-N7Gua, 27% DBC-5-N7Ade, and 9% DBC-5-N3Ade. Thus, activation of DBC by cytochrome P450 predominantly forms depurinating adducts by one-electron oxidation.

Animals↗

PubMed1997

Regulation of N-acetylglucosaminyltransferase V and Asn-linked oligosaccharide beta(1,6) branching by a growth factor signaling pathway and effects on cell adhesion and metastatic potential.

Recent evidence demonstrates that the changes in the size of N-linked oligosaccharides that correlate with cell transformation and tumorigenicity are due at least in part to the regulation of expression of a glycosyltransferase involved in the branching of N-linked structures, N-acetylglucosaminyltransferase V or GlcNAc-T V. Studies have shown that the increases in GlcNAc-T V expression after oncogenic transformation are most likely caused by direct effects on the GlcNAc-T V promoter by the Ets family of transcriptional activators, which are up-regulated by a cellular proliferation signaling pathway. This pathway begins with growth factor receptors that activate tyrosine kinases at the cell surface and proceeds through src, ras, and raf. Additional evidence for the association between cellular proliferation and GlcNAc-T V expression will be presented, as well as a discussion of the effects of beta(1,6) branching on several of the phenotypes of oncogenically transformed cells, including metastatic potential.

Animals↗

PubMed1997

ACE inhibition by enalaprilate stimulates duodenal mucosal alkaline secretion via a bradykinin pathway in the rat.

The effects of enalaprilate on duodenal mucosal alkaline secretion (in situ titration) and mean arterial blood pressure were investigated in chloralose-anesthetized male rats. A bolus injection of enalaprilate (0.7 mg/kg intravenously) increased alkaline secretion by about 60%, and this response was resistant to guanethidine (5 mg/kg intravenously), splanchnicotomy, and vagotomy. Furthermore, angiotensin II infusion (0.25-2.5 microg/kg/hr intravenously) following the administration of enalaprilate failed to influence this response. Bradykinin (10(-6)-10(-4) M) applied topically to the serosal surface of the duodenal segment under study increased dose-dependently the duodenal mucosal alkaline secretion, an effect that could be blocked by the selective bradykinin receptor subtype-2 antagonist HOE140 (100 nmol/kg intravenously). HOE140 also antagonized the response to enalaprilate. These data suggest that enalaprilate increases duodenal mucosal alkaline secretion via a local bradykinin pathway involving receptors of the bradykinin receptor subtype-2 antagonist, rather than by blockade of endogenous angiotensin II or by central autonomic neural regulation.

Adrenergic beta-Antagonists↗

PubMed1997

Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors.

The 4-1BB glycoprotein is a member of the tumor necrosis factor receptor superfamily and binds to a high-affinity ligand (4-1BBL) expressed on several antigen-presenting cells such as macrophages and activated B cells. Expression of 4-1BB is restricted to primed CD4+ and CD8+ T cells, and 4-1BB signaling either by binding to 4-1BBL or by antibody ligation delivers a dual mitogenic signal for T-cell activation and growth. These observations suggest an important role for 4-1BB in the amplification of T cell-mediated immune responses. We now show that administration of anti-4-1BB monoclonal antibodies can eradicate established large tumors in mice, including the poorly immunogenic Ag104A sarcoma and the highly tumorigenic P815 masto cytoma. The immune response induced by anti-4- 1BB monoclonal antibodies is mediated by both CD8+ and CD4+ T cells and is accompanied by a marked augmentation of tumor-selective cytolytic T-cell activity. Our data suggest that a similar approach may be efficacious for immunotherapy of human cancer.

Animals↗

PubMed1997

Induction of antigen-specific antitumor immunity with adenovirus-transduced dendritic cells.

Transduction of dendritic cells (DC) can result in presentation of tumor-associated antigens and induction of immunity against undefined epitopes. The present studies demonstrate adenovirus (Ad)-mediated transduction of the beta-galactosidase gene in mouse DC. Similar transductions have been obtained with the gene encoding the DF3/MUC1 tumor-associated antigen. We show that the Ad-transduced DC are functional in primary allogeneic mixed lymphocyte reactions. Mice immunized with Ad-transduced DC develop cytotoxic T lymphocytes that are specific for the beta-galactosidase or DF3/MUC1 antigens. The results also demonstrate that Ad MUC1-transduced DC induce a specific response which inhibits the growth of DF3/MUC1-positive tumors. These findings support the usefulness of Ad-transduced DC for in vivo immunization against tumor-associated antigens.

Adenoviridae↗

PubMed1997

Effects of periodic obstructive apnoeas on superior and inferior venous return in dogs.

Obstructive apnoeas could cause flow limitation to venous return, resulting in a decrease in cardiac output and a change in the distribution of flow from the upper and lower body. In 14 anaesthetized dogs, we studied the effects of obstructive apnoeas on inferior and superior vena caval flows under baseline conditions and with intra-abdominal pressure increased by approximately equal to 5 torr by binding the abdomen. During obstructive apnoeas in the two groups, respiratory rate decreased by 30% (P < 0.02) and inspiratory airway pressure decreased by approximately equal to 15 torr (P < 0.01). At baseline, the ratio of inferior to superior vena caval flow was 2.4:1 and did not change with abdominal binding or apnoeas. During apnoeas there was no change in cardiac output or in the ratio of inferior to superior vena cava flow either with baseline or abdominal binding conditions. Preservation of total inferior vena caval flow during apnoeas and cardiac output occurred, even though inspiratory flow limitation was found with the abdomen bound. We conclude: (1) there was no change in either cardiac output or the distribution of venous return during apnoeas; (2) there was substantial inspiratory/expiratory variation in venous return during obstructive apnoeas. The large inspiratory-increase in venous return may have implications for the development of pulmonary hypertension during obstructive apnoeas.

Animals↗

PubMed1997

Promoter elements required for phloem-specific gene expression from the RTBV promoter in rice.

Previous studies indicated that a DNA fragment comprising nucleotides (nt) -164 to +45 of the RTBV promoter is sufficient to drive phloem-specific expression of a reporter gene in transgenic rice plants. In addition, two potential cis elements, Box I (nt -3 to +5) and Box II (nt -53 to -39) were identified by DNA-protein interaction assays. In this study, the results of further in vivo studies involving mutagenesis of selected DNA sequences and analysis of expression of a reporter gene in transgenic rice plants revealed that, in addition to Box I and Box II, other elements are required for phloem-specific gene expression, among which are a direct repeat (ASL Box, nt -98 to -79) and a GATA motif (nt -143 to -135). All the these elements bind rice nuclear factors specifically, and mutations of the elements were identified that resulted in loss-of-competition in electrophoretic mobility shift assays. A DNA fragment comprising nt -164 to -32, which contains Box II, the ASL Box and the GATA motif, conferred phloem-specific reporter gene expression independent of Box I when fused to a heterologous CaMV 35S minimal promoter and introduced to transgenic rice plants. Studies that introduced point mutations suggested that in the context of the -103 to +45 promoter fragment, Box II and the ASL Box act synergistically to confer tissue-specific gene expression. Similar studies in the -164 to +45 promoter fragment indicated that the -164 to -103 region, which includes the GATA motif, contains sequences that are functionally redundant with those in the -103 to -32 region, including the ASL Box and Box II. It is concluded that these regions act additively to direct phloem-specific gene expression.

Badnavirus↗

PubMed1997

Scorpion venom leads to gastrointestinal ischemia despite increased oxygen delivery in pigs.

OBJECTIVES: Scorpion envenomation may be accompanied by metabolic acidosis even in the absence of hypoxia and cardiovascular derangement. We tested the hypothesis that venom causes ischemia of the gastrointestinal tract rather than failure of delivery of oxygen to the periphery. DESIGN: Repeated measures, prospective study in experimental animals. SETTING: University-affiliated hospital research laboratory. INTERVENTIONS: In ten spontaneously breathing, intubated, sedated pigs, purified dried venom (Leiurus quinquestriatus), 0.05 mg/kg, was administered intravenously. Measurements were obtained before (baseline), and 5, 15, 30, 60, 120, 180, and 240 mins after injection. MEASUREMENTS AND MAIN RESULTS: Variables measured included: mean arterial pressure (MAP), heart rate (HR), mean pulmonary arterial pressure, pulmonary artery occlusion pressure, cardiac output, stroke volume, right ventricular ejection fraction (rapid thermistor), left ventricular dimensions (echocardiography), arterial gas tensions, lactate and catecholamine concentrations, gastric interstitial mucosal pH (tonometry), as well as systemic and pulmonary vascular resistances. Within 5 mins after venom injection, there was a hyperdynamic state accompanied by significantly increased MAP (97 +/- 18 to 136 +/- 47 mm Hg, p < .0003), HR (70 +/- 12 to 121 +/- 24 beats/min, p < .00006), and cardiac output (1.88 +/- 0.35 to 2.95 +/- 0.53 L/min, p < .0003), with no change in stroke volume, or pulmonary artery occlusion pressure. Right ventricular ejection fraction increased from 38.1 +/- 4.3 to 48.6 +/- 9.0% (p < .0009) by 15 mins. No change in left ventricular function was observed. There were significant decreases in systemic vascular resistance and pulmonary vascular resistance following envenomation. Arterial and gastric mucosal pH significantly decreased from 7.40 +/- 0.04 to 7.25 +/- 0.07 (p < .0001) for arterial pH, and 7.33 +/- 0.08 to 7.17 +/- 0.13 (p < .00001) for gastric mucosal pH by 30 mins after envenomation. The decrease in arterial pH was not sufficient to account for the change in gastric mucosal pH, indicating gastric mucosal ischemia. Arterial lactate increased from 2.6 +/- 1.4 to 7.4 +/- 1.9 (p < .05 x 10(-8)). There were significant increases in serum epinephrine and norepinephrine values by 5 mins. All hemodynamic variables and catecholamine concentrations returned to baseline by 4 hrs. However, there was persistent arterial and gastric mucosal acidosis and increased lactate concentrations even at 4 hrs. Oxygen delivery remained normal or supernormal for 4 hrs following envenomation. However, despite this finding, systemic and gastric mucosal pH changes indicate impaired gastrointestinal oxygen delivery. CONCLUSIONS: Despite increased peripheral oxygen delivery, scorpion envenomation was associated with evidence of ischemia of the gastrointestinal tract. This association could be due to shunting of blood from metabolically active areas, possibly associated with massive catecholamine release, or a direct toxic effect of the venom on regional oxygen transport at the cellular level.

Acidosis↗

PubMed1997

ADHD is associated with early initiation of cigarette smoking in children and adolescents.

OBJECTIVE: The association between attention-deficit hyperactivity disorder (ADHD) and cigarette smoking in children and adolescents was evaluated. METHOD: Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (n = 128) and non-ADHD comparison boys (n = 109) followed prospectively for 4 years into mid-adolescence. Information on cigarette smoking was obtained in a standardized manner blind to the proband's clinical status. Cox proportional hazard models were used to predict cigarette smoking at follow-up using baseline characteristics as predictors. RESULTS: ADHD was a significant predictor of cigarette smoking at follow-up into mid-adolescence. Our findings also revealed that ADHD was associated with an early initiation of cigarette smoking. This was the case even after controlling for socioeconomic status, IQ, and psychiatric comorbidity. In addition, among children with ADHD, there was a significant positive association between cigarette smoking and conduct, major depressive, and anxiety disorders. CONCLUSIONS: ADHD, particularly the comorbid subtype, is a significant risk factor for early initiation of cigarette smoking in children and adolescents. Considering the prevalence and early childhood onset of ADHD, these findings highlight the importance of smoking prevention and cessation programs for children and adolescents with ADHD.

Adolescent↗

PubMed1997

Predicting desipramine levels in children and adolescents: a naturalistic clinical study.

OBJECTIVE: To determine the predictability and stability of desipramine (DMI) concentrations in a clinically treated sample of children, estimating the risk of developing potentially toxic DMI levels at a higher dose after a most recent level in a clinically acceptable range. METHOD: Subjects were 90 consecutive psychiatrically referred children and adolescents treated with DMI with at least two assays of serum DMI concentrations (462 pairs). Assay data were analyzed after log transformation and linear regression. RESULTS: Despite wide between-patient variability in serum DMI levels at the same dose, future within-subject DMI blood levels were highly predictable from knowledge of current levels, current dose, and the future dose. When the DMI serum level was 200 to 300 ng/ml, there was a 7.0% risk for subsequent levels at the same dose to exceed 300 ng/mL, but potentially toxic levels above 500 ng/mL were very infrequent (1.7%). CONCLUSIONS: Although the results of this naturalistic clinical study may not generalize to other situations, the results indicate a reasonable stability, predictability, and safety of DMI levels in individual psychiatrically treated children that result from clinically chosen dose changes.

Adolescent↗

PubMed1997

LHT1, a lysine- and histidine-specific amino acid transporter in arabidopsis.

We have identified a new amino acid transporter from the Arabidopsis thaliana expressed sequence tag cDNA collection by functional complementation of a yeast amino acid transport mutant. Transport analysis of the expressed protein in yeast shows that it is a high-affinity transporter for both lysine (Lys) and histidine with Michaelis constant values of 175 and 400 microM, respectively. This transporter (LHT1, lysine histidine transporter) has little affinity for arginine when measured directly in uptake experiments or indirectly with substrate competition. The cDNA is 1.7 kb with an open reading frame that codes for a protein with 446 amino acids and a calculated molecular mass of 50.5 kD. Hydropathy analysis shows that LHT1 is an integral membrane protein with 9 to 10 putative membrane-spanning domains. Southern-blot analysis suggests that LHT1 is a single-copy gene in the Arabidopsis genome. RNA gel-blot analysis shows that this transporter is present in all tissues, with the strongest expression in young leaves, flowers, and siliques. Wholemount, in situ hybridization revealed that expression is further localized on the surface of roots in young seedlings and in pollen. Overall, LHT1 belongs to a new class of amino acid transporter that is specific for Lys and histidine, and, given its substrate specificity, it has significant promise as a tool for improving the Lys content of Lys-deficient grains.

Amino Acid Sequence↗

PubMed1997

EMF genes regulate Arabidopsis inflorescence development.

Mutations in EMBRYONIC FLOWER (EMF) genes EMF1 and EMF2 abolish rosette development, and the mutants produce either a much reduced inflorescence or a transformed flower. These mutant characteristics suggest a repressive effect of EMF activities on reproductive development. To investigate the role of EMF genes in regulating reproductive development, we studied the relationship between EMF genes and the genes regulating inflorescence and flower development. We found that APETALA1 and AGAMOUS promoters were activated in germinating emf seedlings, suggesting that these genes may normally be suppressed in wild-type seedlings in which EMF activities are high. The phenotype of double mutants combining emf1-2 and apetala1, apetala2, leafy1, apetala1 cauliflower, and terminal flower1 showed that emf1-2 is epistatic in all cases, suggesting that EMF genes act downstream from these genes in mediating the inflorescence-to-flower transition. Constitutive expression of LEAFY in weak emf1, but not emf2, mutants increased the severity of the emf phenotype, indicating an inhibition of EMF activity by LEAFY, as was deduced from double mutant analysis. These results suggest that a mechanism involving a reciprocal negative regulation between the EMF genes and the floral genes regulates Arabidopsis inflorescence development.

Alleles↗

PubMed1997

A strong association between HLA-B*5101 and Behçet's disease in Greek patients.

Behçet's disease is known to be associated with HLA-B51, one of the split antigens of HLA-B5, among many different ethnic groups. In a Greek population, an increased incidence of HLA-B5 in the patient group has also been reported. Because the B51 antigen has been recently identified to comprise seven alleles, B*5101-B*5107, we performed HLA-B51 allele genotyping by the PCR-SSP method as well as serological HLA-A and -B typing among 31 Greek patients with Behçet's disease to investigate whether there is any correlation between one particular B51-associated allele and Behçet's disease. The frequency of B51 was remarkably high (80.6%) in the patient group as compared to the ethnically matched control group (26.7%). In addition, HLA-A26 was also increased in the patients (29.0%) as compared with the healthy controls (3.3%). B51 allele genotyping revealed that all these B51-positive patients carried B*5101. This study revealed a strong association of Behçet's disease in Greeks with one of the B51 subantigens, providing insight into the molecular mechanism underlying an HLA association with Behçet's disease.

Behcet Syndrome↗