Statistical tests for the Gaussian nature of primordial fluctuations through CBR experiments.
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Journal Article↗
Biomedical subjects
X Luo
Publications and source records attributed to X Luo.
Roles of CCAAT/enhancer-binding protein and its binding site on repression and derepression of acetyl-CoA carboxylase gene.
The gene for acetyl-CoA carboxylase, the rate-limiting enzyme in the biosynthesis of long-chain fatty acids, contains two distinct promoter regions, denoted PI and PII, which control the generation of different forms of mRNA. Multiple forms of acetyl-CoA carboxylase (ACC) mRNA with 5'-end heterogeneity are generated as a result of differential splicing of two primary transcripts formed under the control of these two promoters. PI is responsible for the generation of class I mRNAs of ACC, which are induced in a tissue-specific manner under lipogenic conditions. PII generates class II mRNAs of ACC, which are expressed constitutively. Possible mechanisms for the regulation of PI under normal physiological conditions and agents that activate the promoter have been investigated. PI contains a TATA and a CCAAT box. In addition to these sequences, this promoter contains a 28-CA repeat sequence 220 bases upstream from the transcription initiation site; the presence of this sequence leads to about 70% repression of the basal promoter activity. Repression by the 28-CA repeat sequence requires the GCAAT sequence in the CCAAT box. The negative effect of the 28-CA repeat sequence is relieved by a CCAAT/enhancer-binding protein (C/EBP), which binds to the GCAAT sequence. Insertion of the 28-CA repeat sequence into the thymidine kinase promoter results in repression that can also be relieved by the C/EBP gene product. However, the same sequence exerts no effect on ACC promoter II, which has no CCAAT box. During the differentiation of 30A5 preadipocytes into adipocytes, the expression of class I ACC mRNA and C/EBP mRNA is coordinately increased. Therefore, the presence of the CA repeat in the promoter may be responsible for the inactivity of PI, and C/EBP may be one of the factors that is responsible for the activation of PI under lipogenic conditions. Interaction of the CA repeat and the CCAAT box in the repression and derepression of the ACC gene provides a novel function for the CCAAT box and C/EBP in gene regulation.
Acetyl-CoA Carboxylase↗
Ligand-induced domain motion in the activation mechanism of a G-protein-coupled receptor.
Rapidly accumulating information about the structures and functions of transmembrane proteins in the class of G-protein-coupled receptors is facilitating the exploration of molecular details in the processes of cellular signal transduction. We have described recently a 3-D molecular model of the transmembrane portion of the 5-HT2A type of receptor of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT), constructed from such convergent empirical and theoretical considerations, and have used it for a computational simulation of the mechanisms of ligand-induced receptor activation and signal transduction. The molecular dynamics (MD) simulation of the interaction between the receptor model and ligands of different pharmacological efficacies pointed to a set of specific conformational changes propagated from the ligand binding site to a distal region of the receptor that is essential for signal transduction. The ligand-induced changes were found to correlate well with the known pharmacological properties, but it remained unclear how the binding of the small 5-HT2A receptor agonist molecules in the distal binding pocket could give rise to the specific conformational changes in a distant part of the receptor. As the MD simulations showed the secondary structure of the helical transmembrane domains of the receptor to be well maintained, and the conformational changes to involve mainly translations and rotations of the helices in the bundle relative to one another, an algorithm was developed to treat the ligand-induced conformational changes as rigid domain movements of transmembrane helices.(ABSTRACT TRUNCATED AT 250 WORDS)
Binding Sites↗
Stress-specific regulation of corticotropin releasing hormone receptor expression in the paraventricular and supraoptic nuclei of the hypothalamus in the rat.
Corticotropin releasing hormone (CRH), a major regulator of pituitary ACTH secretion, also acts as a neurotransmitter in the brain. To determine whether CRH is involved in the regulation of hypothalamic function during stress, CRH receptor binding and CRH receptor mRNA levels were studied in the hypothalamus of rats subjected to different stress paradigms: immobilization, a physical-psychological model; water deprivation and 2% saline intake, osmotic models; and i.p. hypertonic saline injection, a combined physical-psychological and osmotic model. In agreement with the distribution of CRH receptor binding in the brain, in situ hybridization studies using 35S-labeled cRNA probes revealed low levels of CRH receptor mRNA in the anterior hypothalamic area, which were unaffected after acute or chronic exposure to any of the stress paradigms used. Under basal conditions, there was no CRH binding or CRH receptor mRNA in the supraoptic (SON) or paraventricular (PVN) nuclei. However, 2 h after the initiation of acute immobilization, CRH receptor mRNA hybridization became evident in the parvicellular division of the PVN, with levels substantially increasing from 2 to 4 h, decreasing at 8 h and disappearing by 24 h. Identical hybridization patterns of CRH receptor mRNA were found in the parvicellular PVN after repeated immobilization; levels were similar to those after 2 h single stress following immobilization at 8-hourly intervals for 24 h (3 times), and very low, but clearly detectable 24 h after 8 or 14 days daily immobilization for 2 h. On the other hand, water deprivation for 24 or 60 h and intake of 2% NaCl for 12 days induced expression of CRH receptor mRNA in the SON and magnocellular PVN, but not in the parvicellular pars of the PVN.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The cellular transcription factor USF cooperates with varicella-zoster virus immediate-early protein 62 to symmetrically activate a bidirectional viral promoter.
The mechanisms governing the function of cellular USF and herpesvirus immediate-early transcription factors are subjects of considerable interest. In this regard, we identified a novel form of coordinate gene regulation involving a cooperative interplay between cellular USF and the varicella-zoster virus immediate-early protein 62 (IE 62). A single USF-binding site defines the potential level of IE 62-dependent activation of a bidirectional viral early promoter of the DNA polymerase and major DNA-binding protein genes. We also report a dominant negative USF-2 mutant lacking the DNA-binding domain that permits the delineation of the biological role of both USF-1 and USF-2 in this activation process. The symmetrical stimulation of the bidirectional viral promoter by IE 62 is achieved at concentrations of USF-1 (43 kDa) or USF-2 (44 kDa) already existing in cells. Our observations support the notion that cellular USF can intervene in and possibly target promoters for activation by a herpesvirus immediate-early protein.
Base Sequence↗
Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience.
PURPOSE AND METHODS: We reviewed the clinical records and pathologic findings of 37 children and adolescents with synovial sarcoma treated at our institution over a 30-year period to evaluate the prognostic significance of tumor size, invasiveness, histology, and other features. RESULTS: The 20 male and 17 female patients with synovial sarcoma had a median age of 13.7 years at diagnosis. Primary tumor sites were the extremities (n = 27), trunk (n = 8), and head and neck (n = 2). Disease stage (clinical group) was as follows: group I, n = 21; group II, n = 7; group III, n = 4; and group IV, n = 5. Nineteen patients had invasive (T2) lesions, 20 had tumors more than 5 cm in diameter, and 14 had histologic grade 3 lesions. The estimated 5-year survival rate (+/- SE) for patients with group I or II disease was 80% +/- 9%, compared with 17% +/- 15% for those with group III or IV tumors (P = .0003). An exact log-rank test, adjusted for clinical group, showed that tumor invasiveness and grade independently predicted overall and progression-free survival (P < .05); tumor size was significantly correlated with progression-free survival. A borderline significant relationship with overall survival was found for both tumor size and histologic subtype (P = .09). CONCLUSION: A controlled trial of adjuvant chemotherapy is merited in children with resected synovial sarcoma (clinical group I or II) who present with unfavorable clinicopathologic features such as large, invasive, or grade 3 lesions. Children with unresected or metastatic disease fare poorly despite multimodality therapy and require novel treatment approaches.
Adolescent↗
Role of MB isoforms (isomers) in the early diagnosis of acute myocardial infarction.
In addition to electrocardiogram (ECG), analysis of creatinine phosphokinase (CPK), lactate dehydrogenase (LDH) and their isoenzymes is commonly employed to diagnose acute myocardial infarction (AMI). The aim of this study was to observe the efficiency of isomers of CPK for early diagnosis of AMI. ECG, though useful in many ways, is not 100% sensitive. The drawback involved with CPK and LDH isoenzymes is the time lag factor in diagnosing AMI early enough for interventional therapy. Recently the subunits of these isoenzymes, namely MM and now the MB isomers are being tested for their effectiveness in the early diagnosis of AMI. In our experience MB isomers were found to be accurate markers in the early diagnosis of AMI. They were especially valuable in diagnosing myocardial infarction not detectable by ECG in cases such as non-Q AMI, cardiomyopathy, and bundle branch block among other such cases.
Clinical Enzyme Tests↗
[Haemodynamic changes and clinic significance in primary pigmentary degeneration of retina].
In comparison with 40 healthy controls, the blood viscosity and erythrocystic agglutination index were predominantly higher in 44 cases with primary pigmentary degeneration. It is believed that the changes mentioned above may result in general and local circulatory disturbance, leading the tissue to ischeia, anoxia and a series of other pathological changes; and exacerbating the functional damage of retina. The author suggests that primary pigmentary degeneration of retina may be treated with the drugs which can lower the blood viscosity, the concentration of blood cholesterol and lipid, and increase blood-dynamics.
Adult↗
Ethnic differences in erythrocyte catechol-O-methyltransferase activity in black and white Americans.
Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catecholamine and catechol drugs such as levodopa and methyldopa. Human COMT activity is inherited as an autosomal co-dominant trait; approximately 25% of white individuals have low activity consistent with homozygosity for a low activity allele, about 50% have intermediate activity (i.e., heterozygous genotype) and 25% have high activity. COMT activity has not been characterized in African-Americans or other black populations. To investigate potential ethnic and gender differences in COMT, we measured erythrocyte COMT activity in 195 unrelated black and 202 unrelated white healthy individuals living in the Southeast United States. Overall, the black population had significantly higher COMT activity than the white population (median 15.7 vs. 11.4 U/ml of packed red blood cell volume; P < .001). Maximum likelihood estimation of COMT activity distribution identified significant ethnic differences, with high activity in 23% of whites and 55% of blacks, intermediate activity in 50% of whites and 38% of blacks and low activity in 27% of whites and 7% of blacks. No greater differences in COMT activity were observed in either ethnic group. We conclude that red blood cell COMT activity is significantly higher in black subjects than white subjects. Hardy-Weinberg estimates indicate that this ethnic difference is due to a higher frequency of high activity COMT alleles in blacks vs. whites (0.74 vs. 0.48).
Adolescent↗
[Chemiluminescent immunoassay for anti-granulocyte antibody IgG].
In this paper is reported solid phase competitive chemiluminescent immunoassay (CLIA) for anti-granulocyte antibody (AGAb) IgG with N-(4-amiobytul)-N-ethylisoluminol (ABEI) labelled rabbit antibody IgG against granulocyte competing with the analyte and ABEI-CoCl2-H2O2 as the chemiluminescent system. The absolute limit of detection was 3.0 x 10(-14) mol ABEI/tube. One hundred and thirty one individuals were divided into three groups: leukocytopenic group (n = 58), control group (n = 41) and normal group (n = 32). Chemiluminescent index (CLI) was used as the diagnostic criterion for AGAb in serum. The results showed that the positive rate of the leukocytopenic group was significantly higher than that of the control group (P < 0.005), and the sensitivity, specificity and accuracy of the method were 43.1%, 90.2% and 62.6%, respectively.
Granulocytes↗
Influence of alloferin on neuromuscular function in myasthenia patients undergoing thymectomy.
Myasthenia gravis patients are hypersensitive to nondepolarizing relaxants, such as alcuronium, an intermediate-long nondepolarizing agent. This study observed the effects of alcuronium treatment in myasthenia gravis patients as compared with non-MG patients during operation. Ten MG patients (Ossermann class I-IV, scheduled for thymectomy) and 10 non-MG patients (ASA class I-II, scheduled for operation) were selected. An induction dose of alcuronium 0.2 mg/kg and thiopental 4-6 mg/kg was given, followed by intubation and ventilation with 50% nitrous oxide in oxygen and 0.5-1.5% ethrane. Neuromuscular transmission was monitored using an accelerograph and degrees of neuromuscular function at different depths were recorded. There were statistically significant differences between the two groups. The effect of alloferin in the MG group was quicker and deeper. This study also found a relation between MG class and the recovery of respiration: Respiratory recovery was quicker in classes I-II than in classes III-IV.
Adult↗
Testing for the Gaussian nature of cosmological density perturbations through the three-point temperature correlation function.
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Journal Article↗
Serum intercellular adhesion molecule-1 in childhood malignancy.
Levels of soluble intercellular adhesion molecule-1 (ICAM-1) were measured in serum samples taken at diagnosis from pediatric patients with Hodgkin's disease (n = 69), acute lymphoblastic leukemia (n = 28), Wilms' tumor (n = 20), osteosarcoma (n = 17), rhabdomyosarcoma (n = 18), or Ewing's sarcoma (n = 15). Median levels of serum ICAM-1 were significantly higher in acute lymphoblastic leukemia and Hodgkin's disease than in controls and other malignancies. Levels were positively correlated with disease stage for patients with Hodgkin's disease, Ewing's sarcoma or Wilms' tumor, and with the frequency of relapse in Hodgkin's disease (P = .016). Serum levels were normal in all of 76 patients tested in remission. It remains to be determined whether increased serum ICAM-1 levels simply reflect a greater tumor burden or whether this molecule contributes directly to the progression of childhood malignancies.
Adolescent↗
Vitamin D deficiency suppresses cell-mediated immunity in vivo.
Severe vitamin D deficiency has been produced in mice as evidenced by severe hypocalcemia and an absence of 25-hydroxyvitamin D in blood. Vitamin D deficiency was accompanied by a slight decrease in body weight and food consumption. Vitamin D-deficient and vitamin D-sufficient mice were sensitized with dinitrofluorobenzene (DNFB). Sensitivity to DNFB was determined by treatment of one ear with DNFB. The ratio of thickness of the treated ear to that of nontreated ear was used as an index of cell-mediated immune reaction. The incorporation of [3H]thymidine into the DNA of the ear was also used as an index of cell-mediated immunity as was the response of thymus lymphocytes to concanavalin A. Vitamin D deficiency markedly decreased the ear thickness ratio and the [3H]thymidine incorporation ratio in DNFB-sensitized mice. Similarly, the incorporation of [3H]thymidine into the DNA of concanavalin A-treated thymus lymphocytes from DNFB-sensitive mice was significantly reduced in vitamin D deficiency. These results show that in vivo vitamin D deficiency impairs cell-mediated immunity. The provision of a vitamin D-sufficient diet for 8 weeks corrected the impaired response of the immune system, while vitamin D administration for 3 weeks did not.
Animals↗
The tyrosine residue at position 97 in the VH CDR3 region of a mouse/human chimeric anti-colorectal carcinoma antibody contributes hydrogen bonding to the TAG72 antigen.
One amino acid, tyrosine at position 96 and 97 in the VH CDR3 region of a mouse/human chimeric anti-TAG72 antibody cB72.3m4 was substituted by the phenylalanine residue and by a number of amino acids from different amino acid groups by the site-directed mutagenesis technique. The expression vector mpSV2neo-EP1-Vm11-16C1 containing mutant VH region fragments (Vm11-16) as well as the immunoglobulin enhances (E), promoter (P1) and the human genomic C1 region fragments, were transfected into a heavy-chain-loss mutant cell line B72.3Mut(K), respectively. Mutant chimeric cB72.3m11-16 antibodies were purified from the transfectant supernates and compared based upon their binding affinity for the TAG72 antigen relative to that of the original cB72.3m4 antibody. The data showed that a single amino acid substitution of tyrosine by phenylalanine and a number of amino acids including serine, asparagine, histidine and arginine at position 97 in the VH CDR3 region all resulted in approximate 18-fold lower binding affinity, whereas the substitution of tyrosine by phenylalanine at position 96 in the VH CDR3 region did not affect the binding affinity of the cB72.3m4 antibody. This suggests that the tyrosine residue at position 97 in the VH CDR3 region is in a contact position in the B72.3/TAG72 antibody/antigen interaction, and that the terminal hydroxyl group of the position 97 tyrosine side-chain contributes hydrogen bonding to the TAG72 antigen, whereas the position 96 tyrosine side-chain does not.
Animals↗
Recombinant bifunctional molecule FV/IFN-gamma possesses the anti-tumor FV as well as the gamma interferon activities.
Recombinant DNA techniques were used to clone, construct and express the bifunctional molecule FV/IFN-gamma. The FV/IFN-gamma is a single-chain 42KD fusion protein expressed in E. coli under control of the strong T7 bacteriophage promoter in the expression vector pT7-7-FV-IFN-gamma. The fused gene fragment FV-IFN-gamma containing a single-chain anti-TAG72 FV gene fragment as well as the human recombinant cDNA fragment of IFN-gamma molecule. The renatured soluble form of FV/IFN-gamma was purified from E. coli inclusion bodies using HTPT chromatography. The yield of this fusion protein was estimated at 10mg/L. Our data showed that the FV/IFN-gamma molecule retained the TAG72 antigen-binding specificity and the IFN-gamma activity as measured in ELISA, Western blotting and up-regulation of CEA expression by IFN-gamma. Therefore, it may prove to be useful in targeting the biological effect of IFN-gamma to tumor cells and stimulating its immune destruction.
Antigens, Neoplasm↗
Tumor-cell DNA content predicts outcome in children and adolescents with clinical group III embryonal rhabdomyosarcoma. The Intergroup Rhabdomyosarcoma Study Committee of the Children's Cancer Group and the Pediatric Oncology Group.
PURPOSE: The prognostic value of tumor-cell DNA content (ploidy) was evaluated in children with unresectable, nonmetastic rhabdomyosarcoma of embryonal histology. PATIENTS AND METHODS: Flow-cytometric techniques were used to estimate the ploidy of tumor specimens from 34 patients with embryonal rhabdomyosarcoma who were enrolled in the intergroup rhabdomyosarcoma study III (IRS III) from 1985 to 1991. Tumors were classified as diploid or hyperdiploid (DNA content, 1.1 to 1.8 times that of normal diploid cells). The influence of ploidy on clinical outcome was assessed by the Kaplan-Meier technique and Cox regression analysis with stepwise selection. RESULTS: Twelve of the tumor specimens were diploid and 22 were hyperdiploid. The patient groups defined by diploid or hyperdiploid tumors had similar presenting characteristics (eg, age, tumor size, and anatomic site). Significantly more children with hyperdiploid tumors achieved a complete response than did children with diploid tumors (85% v 42%; P = .01). The probability of progression-free survival at 5 years (+/- SE) was 91% +/- 6% for the hyperdiploid group, compared with 17% +/- 11% for the diploid group (P < .001). Hyperdiploidy was also associated with a significantly higher overall survival rate at 5 years: 96% +/- 4% versus 50% +/- 14% (P = .004). Ploidy retained its prognostic significance after adjustment for tumor site in the Cox regression model. CONCLUSION: Tumor-cell ploidy strongly correlates with outcome in children with nonmetastic, unresectable embryonal rhabdomyosarcoma. The two biologically distinct groups identified by this measure would benefit from further refinements in risk-directed therapy.
Adolescent↗
Characterization of the mouse FTZ-F1 gene, which encodes a key regulator of steroid hydroxylase gene expression.
The cytochrome P450 steroid hydroxylases are coordinately regulated by steroidogenic factor 1 (SF-1), a protein expressed selectively in steroidogenic cells. Based on its expression in steroidogenic tissues and DNA-binding specificity, we isolated a putative SF-1 cDNA from an adrenocortical cDNA library. As evidence that this cDNA encodes SF-1, we now show that it is selectively expressed in steroidogenic cells, that an antiserum against its protein product specifically abolishes the SF-1-related gel-shift complex, and that its coexpression increases promoter activity of the 21-hydroxylase 5'-flanking region in transfection experiments. Sequence analyses of the SF-1 cDNA revealed that it is the mouse homolog of fushi tarazu factor I (FTZ-F1), a nuclear receptor that regulates the fushi tarazu homeobox gene in Drosophila. A second FTZ-F1 homolog, embryonal long terminal repeat-binding protein (ELP), was recently isolated from embryonal carcinoma cells. SF-1 and ELP cDNAs are virtually identical for 1017 base pairs, including putative DNA-binding domains, but diverge at their 5'- and 3'-ends. One genomic clone contained both SF-1- and ELP-specific sequences, confirming their origin from a single gene. Characterization of this gene defined shared exons encoding common regions and alternative promoters and 3'-exons leading to differences between the two FTZ-F1 transcripts. We used in situ hybridization with transcript-specific probes to study the ontogeny of SF-1 and ELP expression. ELP transcripts were not detected from embryonic day 8 to adult, consistent with its previous isolation from embryonal carcinoma cells and its postulated role in early embryonic development.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Cortex Neoplasms↗