SEARCH · PubMed Health

Results for “variable methylation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources

PubMed2001

Wound-inducible proteinase inhibitors in pepper. Differential regulation upon wounding, systemin, and methyl jasmonate.

Seven small (approximately 6,000 D) wound-inducible proteinase inhibitor proteins were isolated from leaves of pepper (Capsicum annuum) plants that are members of the potato inhibitor II family. N-terminal sequences obtained indicated that the pepper leaf proteinase inhibitors (PLPIs) exhibit homology to two GenBank accessions that code for preproteins containing three isoinhibitors domains each that, when post-translationally processed, can account for the mixture of isoinhibitors that are reported herein from pepper leaves. A constitutive level of PLPI proteins was found in pepper leaves, and these levels increased up to 2.6-fold upon wounding of the lower leaves. Exposing intact plants to methyl jasmonate vapors induced the accumulation of PLPIs. Supplying excised young pepper plants with water through the cut stems induced PLPI proteins to levels higher than those found in intact plants, but with high variability. Supplying the excised plants with systemin did not result in an increase of PLPI levels that were statistically higher than levels found in excised plants. Gel-blot analyses of PLPI induction revealed the presence of two mRNA bands, having slightly different mobilities in agarose gels. Only the low M(r) mRNA is present in untreated control plants, and it appears to be responsible for the constitutive levels of PLPI found in leaves. Both mRNA species are wound- and methyl jasmonate-inducible. Only the low- M(r) species is weakly induced by systemin, indicating a differential expression of the two PLPI species.

Acetates↗

PubMed2003

Maternal alleles acquiring paternal methylation patterns in biparental complete hydatidiform moles.

We previously mapped a maternal locus responsible for biparental complete hydatidiform moles (BiCHMs) to 19q13.4. The two index patients had a total of 14 molar pregnancies, eight abortions at various developmental stages, and one 16-year-old healthy offspring. We suggested that the defective gene deregulates the expression of imprinted genes. Here, we report the methylation status of four imprinted genes in two BiCHMs from the two sisters, the 16-year-old normal offspring, and two sporadic BiCHMs from unrelated patients. Using two bisulfite-based methods, we demonstrate a general trend of abnormal hypomethylation at the paternally expressed genes, PEG3 and SNRPN, and hypermethylation at the maternally expressed genes, NESP55 and H19, in two to four BiCHMs. Using single nucleotide polymorphisms, we provide the first evidence that SNRPN, NESP55 and H19 are abnormally methylated on the maternal alleles in BiCHMs. We show, in the BiCHMs from the two sisters, that the abnormally methylated H19 allele is inherited from either the maternal grandmother or the maternal grandfather. These data suggest that the abnormal methylation in BiCHMs is not due to an error in erasing the parental imprinting marks but rather in the re-establishment of the new maternal marks during oogenesis or their postzygotic maintenance. The defective 19q13.4 locus may have led to the development of variable degrees of 'faulty' paternal marks on the maternal chromosomes.

Adolescent↗

PubMed1998

Interstitial duplications of chromosome region 15q11q13: clinical and molecular characterization.

Duplications of chromosome region 15q11q13 often occur as a supernumerary chromosome 15. Less frequently they occur as interstitial duplications [dup(15)]. We describe the clinical and molecular characteristics of three patients with de novo dup(15). The patients, two males and one female (ages 3-21 years), had nonspecific findings that included autistic behavior, hypotonia, and variable degrees of mental retardation. The extent, orientation, and parental origin of the duplications were assessed by fluorescent in situ hybridization, microsatellite analyses, and methylation status at D15S63. Two patients had large direct duplications of 15q11q13 [dir dup(15)(q11q13)] that extended through the entire Angelman syndrome/Prader-Willi syndrome (AS/PWS) chromosomal region. Their proximal and distal breaks, at D15S541 or D15S9 and between D15S12 and D15S24, respectively, were comparable to those found in the common AS/PWS deletions. This suggests that duplications and deletions may be the reciprocal product of an unequal recombination event. These two duplications were maternally derived, but the origin of the chromatids involved in the unequal crossing over in meiosis differs. In one patient, the duplication originated from two different maternal chromosomes, while in the other patient it arose from the same maternal chromosome. The third patient had a much smaller duplication that involved only D15S11 and parental origin could not be determined. There was no obvious correlation between phenotype and extent of the duplication in these patients.

Adult↗

PubMed1977

Mathematical model for enteric film coating of tablets.

The enteric film coating of placebo tablets, using a methacrylic acid-methyl methacrylate copolymer as the film former in the coating solution, was studied by statistical techniques. The effects of four independent formulation and process variables on the disintegration time of the coated film in simulated intestinal fluid and on the resistance to disintegration of the coated film in simulated gastric fluid were studied. The results of a statistically designed set of experiments were used as the input data. Regression analysis of these data resulted in two first-order polynomial equations. The linear model obtained for the disintegration time of the coating in the simulated intestinal fluid was analyzed by the steepest descent method to determine the most suitable combination of the independent variables.

Chemistry, Pharmaceutical↗

PubMed2004

Novel variable volume injector for performing sample introduction in a miniaturised isotachophoresis device.

A microdevice design furnished with a novel sample injector, capable of delivering variable volume samples, for miniaturised isotachophoretic separations is presented. Micromachining by direct milling was used to realise two flow channel network designs on poly(methyl methacrylate) chips. Both designs comprised a wide bore sample channel interfaced, via a short connection channel, to a narrow bore separation channel. Superior injection performance was observed with a connection channel angled at 45 degrees to the separation channel compared to a device using a channel angled at 90 degrees. Automated delivery of electrolytes to the microdevice was demonstrated with both hydrostatic pumping and syringe pumps; both gave reproducible sample injection. A range of different sampling strategies were investigated. Isotachophoretic separations of model analytes (metal ions and an anionic dye) demonstrated the potential of the device. Separations of ten metal cations were achieved in under 475 s.

Anions↗

PubMed1997

New fluorogenic substrates for the study of secondary specificity of prolyl oligopeptidase.

The secondary specificity of prolyl oligopeptidase (POP) has been studied by using a series of fluorogenic substrates containing the highly fluorescent 7-amino-4-methyl-2-quinolinone (AMeq) marker. The substrates were dipeptides of the general formula Z-X-Pro-NH-Meq, bearing amino acid residues with variable functional groups [Met, Lys(Boc), Lys, His, Ser, Leu, Glu(OMe), Glu, Cys(Bzl)] at the P2 position, and the tripeptide Z-Asn-Cys(Bzl)-Pro-NH-Meq. The kinetic parameters for their hydrolysis by porcine kidney POP were determined at lambda ex = 360 nm and lambda em = 430 nm. All the dipeptide substrates showed a high affinity to the enzyme and could be used for its fluorometric determination. The S2 binding subsite of POP can accommodate amino acid residues with a bulky side group, while it prefers a positively charged group (free Lys) instead of a negatively charged one (free Glu).

Fluorescent Dyes↗

PubMed1968

Relationship between sugar structure and competition for the sugar transport system in Bakers' yeast.

Twenty-five sugars have been compared as inhibitors of l-sorbose or d-xylose transport by the constitutive, monosaccharide transport system in bakers' yeast. d-Glucose showed the highest activity (i.e., apparent K(i) = 5 mm). Since all sugars except 2-deoxyglucose showed a decrease in activity relative to glucose (i.e., apparent K(i) = 25 - >2,000 mm), an attempt was made to relate the activity of each sugar with the way its structure differs from that of d-glucose. Assuming that the inhibition was the result of sugar-carrier complex formation, the analysis showed that the transport system has a rather broad specificity for pyranoses. Single changes at each of the five carbons of d-glucose (except for the 2-deoxy derivative) result in variable decreases in activity depending upon the carbon number and the alteration. The largest decrease in activity effected by a single change is the methylation or glucosylation of the anomeric hydroxyl. The combination of two or more changes leads to a decrease which is greater than the decrease in activity resulting from the individual changes occurring alone.

Arabinose↗

PubMed2003

FMR2 function: insight from a mouse knockout model.

The FMR2 gene is dysregulated by the fragile X E triplet repeat expansion in patients with FRAXE mental retardation syndrome. A CCG triplet, located in the 5' untranslated region of the FRAXE gene undergoes expansion and methylation in these patients, eliminating detectable gene transcription. FRAXE syndrome is distinct from fragile X syndrome, a more common genetic form of mental retardation caused by expansion and methylation of a similar repeat in the FMR1 gene located 600 kb proximal to FRAXE. FRAXE syndrome is rare, and patients' phenotypes are highly variable, leading to difficulties with predicting specific FMR2 functions based on the human disease. Recently, Lilliputian(Lilli), a Drosophila FMR2 orthologue, was identified; this gene has been linked with several signal transduction pathways, including the transforming growth factor-beta (TGF-beta) pathway, the Raf/MEK/MAP kinase (MAPK) pathway, and the P13K/PKB pathway. Mutation of Lilli shows defects in germinal band extension, cytoskeletal structure, cell growth, and organ development. The Lilli gene suggests possible functions for FMR2 (and related genes) in humans and mice, but cannot predict specific functions. Modeling FMR2 mutation in the mouse will be useful to understand specific functions of this gene in vertebrates. This review presents what has been learned thus far from the FMR2 knockout mouse model and suggests future studies on this model in order to compare it with the human FRAXE mental retardation disorder, Lilli mutants in Drosophila and other mouse models of genes in this family.

Amino Acid Sequence↗

PubMed1987

Effects of specific activation of mu-, delta- and kappa-opioid receptors on the secretion of luteinizing hormone and prolactin in the ovariectomized rat.

With the recent development of highly specific ligands for the mu, delta and kappa opioid receptors it was of interest to define the effects of activation of each of these receptor types on LH and prolactin (PRL) secretion. The compounds were infused (10 microliters/h) at various concentrations into the third cerebroventricle of unanesthetized, ovariectomized rats. The mu agonist, DAGO, at both 1 and 10 micrograms/h caused a significant suppression of LH secretion and a significant stimulation of PRL release. DPDPE, the delta agonist, had no effect on either hormone at 1 microgram/h but inhibited LH secretion at 10 micrograms/h. There was still no effect of this high dose of DPDPE on PRL release. The kappa agonist, U50,488H, had no effect on either hormone at 10 micrograms/h, but at 100 micrograms/h produced a significant suppression of LH release and a highly variable increase in PRL. Coinfusion of 100 micrograms/h of naloxone with the high dose of each of the agonists completely blocked the responses of both hormones to each of the agonists with one exception: the highly variable stimulation of PRL by U50,488H was not affected, thus indicating a nonspecific effect of U50,488H on PRL secretion. These results demonstrate that: activation of the mu receptors produces an inhibition of LH secretion and a stimulation of PRL release; activation of the delta receptors produces an inhibition of LH secretion but has no effect on PRL release, and activation of the kappa receptors produces an inhibition of LH release and a variable stimulation of PRL secretion.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2003

Inverse relationship between bioconcentration factor and exposure concentration for metals: implications for hazard assessment of metals in the aquatic environment.

The bioconcentration factor (BCF) and bioaccumulation factor (BAF) are used as the criteria for bioaccumulation in the context of identifying and classifying substances that are hazardous to the aquatic environment. The BCF/BAF criteria, while developed as surrogates for chronic toxicity and/or biomagnification of anthropogenic organic substances, are applied to all substances including metals. This work examines the theoretical and experimental basis for the use of BCF/BAF in the hazard assessment of Zn, Cd, Cu, Pb, Ni, and Ag. As well, BCF/BAFs for Hg (methyl and inorganic forms) and hexachlorobenzene (HCB) were evaluated. The BCF/BAF data for Zn, Cd, Cu, Pb, Ni, and Ag were characterized by extreme variability in mean BCF/BAF values and a clear inverse relationship between BCF/BAF and aqueous exposure. The high variability persisted when even when data were limited to an exposure range where chronic toxicity would be expected. Mean BCF/BAF values for Hg were also variable, but the inverse relationship was equivocal, in contrast with HCB, which conformed to the BCF model. This study illustrates that the BCF/BAF criteria, as currently applied, are inappropriate for the hazard identification and classification of metals. Furthermore, using BCF and BAF data leads to conclusions that are inconsistent with the toxicological data, as values are highest (indicating hazard) at low exposure concentrations and are lowest (indicating no hazard) at high exposure concentrations, where impacts are likely. Bioconcentration and bioaccumulation factors do not distinguish between essential mineral nutrient, normal background metal bioaccumulation, the adaptive capabilities of animals to vary uptake and elimination within the spectrum of exposure regimes, nor the specific ability to sequester, detoxify, and store internalized metal from metal uptake that results in adverse effect. An alternative to BCF, the accumulation factor (ACF), for metals was assessed and, while providing an improvement, it did not provide a complete solution. A bioaccumulation criterion for the hazard identification of metals is required, and work directed at linking chronic toxicity and bioaccumulation may provide some solutions.

Analysis of Variance↗

PubMed2005

The leukocyte count predicts the efficacy of treatment with azathioprine in inflammatory bowel disease.

INTRODUCTION: Azathioprine has variable efficacy in inflammatory bowel disease. Previous studies suggested that either neutropenia, an increase in the mean corpuscular volume, the assessment of thiopurine methyl-transferase activity or erythrocyte 6-thioguanine values might predict the treatment response. However, due to the conflicting results of the preceding studies there are yet no established laboratory values which allow an estimation of the clinical response. PATIENTS AND METHODS: 45 patients with Crohn's disease and 39 patients with ulcerative colitis were enrolled in this retrospective evaluation. After a minimum of six months therapy with azathioprine patients in remission were compared with those who did not achieve a stable remission with respect to the number of leucocytes, lymphocytes, neutrophil granulocytes and the mean corpuscular volume. RESULTS: Patients who went into remission during treatment with azathioprine displayed significantly lower leukocyte counts if compared to patients who were not in remission (p = 0.004 in Crohn's disease and 0.003 in ulcerative colitis). A similar tendency was also observed with respect to the granulocyte count (p = 0.007 in Crohn's disease and 0.004 in ulcerative colitis). The mean corpuscular volume did not correlate with the response to purine analogues. DISCUSSION: The absolute leukocyte count and the percentage of granulocytes seem to predict the response to purine analogues in inflammatory bowel disease and possibly offers a feasible and cost effective diagnostic tool for the assessment of therapeutic efficacy. Subsequent preferably prospective studies should aim to define the optimal cut-off value for the leukocyte count.

Adult↗

PubMed2000

Genomic imprinting and environmental disease susceptibility.

Genomic imprinting is one of the most intriguing subtleties of modern genetics. The term "imprinting" refers to parent-of-origin-dependent gene expression. The presence of imprinted genes can cause cells with a full parental complement of functional autosomal genes to specifically express one allele but not the other, resulting in monoallelic expression of the imprinted loci. Genomic imprinting plays a critical role in fetal growth and behavioral development, and it is regulated by DNA methylation and chromatin structure. This paper summarizes the Genomic Imprinting and Environmental Disease Susceptibility Conference held 8-10 October 1998 at Duke University, Durham, North Carolina. The conference focused on the importance of genomic imprinting in determining susceptibility to environmentally induced diseases. Conference topics included rationales for imprinting: parental antagonism and speciation; methods for imprinted gene identification: allelic message display and monochromosomal mouse/human hybrids; properties of the imprinted gene cluster human 11p15.5 and mouse distal 7; the epigenetics of X-chromosome inactivation; variability in imprinting: imprint erasure, non-Mendelian inheritance ratios, and polymorphic imprinting; imprinting and behavior: genetics of bipolar disorder, imprinting in Turner syndrome, and imprinting in brain development and social behavior; and aberrant methylation: methylation and chromatin structure, methylation and estrogen exposure, methylation of tumor-suppressor genes, and cancer susceptibility. Environmental factors are capable of causing epigenetic changes in DNA that can potentially alter imprint gene expression and that can result in genetic diseases including cancer and behavioral disorders. Understanding the contribution of imprinting to the regulation of gene expression will be an important step in evaluating environmental influences on human health and disease.

Animals↗

PubMed1991

DNA methylation changes in human testicular cancer.

We previously reported an X/Y imbalance with a relative excess of X- and a relative deficiency of Y-chromosomal DNA in three out of nine testicular tumors of germ cell origin. To study the implications of those changes the methylation status of DNA from seven of the tumors was explored by HpaII/MspI analysis. The 5' regions of the hypoxanthine phosphoribosyltransferase (HPRT) and the phosphoglycerate kinase (PGK) gene loci exhibited main patterns suggestive of active X chromosomes in the tumors. However, a minority of the HPRT loci of one teratocarcinoma with an increased dosage of the X chromosome, as well as one additional teratocarcinoma, revealed patterns analogous to inactive X chromosomes in females. Using probes from several chromosomes it was subsequently found that the teratocarcinoma tumors (3/3) were characterized by generalized hypermethylation. On the contrary, the seminomas showed variable hypomethylation (4/5) or virtually complete demethylation (1/5). The seminoma with the most extensive hypomethylation was disseminated (stage III), whereas the other seminomas were local (stage I). These findings suggest that DNA methylation may play a role in the developmental pathways leading to different histologic types of testicular tumors of germ cell origin. The HPRT results imply that the consequences of extra X chromosomes--a frequent finding in testicular tumors--may be modulated by mechanisms, such as DNA methylation, that control gene activity.

DNA↗

PubMed2003

Baseline characteristics of the transient pattern electroretinogram in non-human primates: inter-ocular and inter-session variability.

This study assessed the inter-ocular and inter-session variability of the transient pattern electroretinogram (PERG) in a group of non-human primates. The transient PERG was measured both eyes of 29 non-human primates, and again after three months in 23 eyes of 23 of these animals. Signals were elicited using a contrast (90%, 75 cdm(-2)) reversing (5 reversals sec(-1)) checkerboard pattern (0.56 cpd). PERGs were also measured for stimuli of varied spatial frequency (n=8, 0.07-2.22 cpd), contrast (n=4, 20-100%), mean luminance (n=4, 4.7-75 cdm(-2)) and defocus (n=5, +1, +2, +3 diopters). The inter-eye and inter-session limits-of-agreement (LOA; 95%) were determined for each PERG parameter. Variability was also compared with previous studies using the coefficient-of-variability (COV). Pharmacological blockade of the inner retinal contributions to the PERG measured under these conditions was conducted in one animal using intravitreal injection of tetrodotoxin (approximately 6 microM) and N-methyl-D-aspartic acid (approximately 6 microM). The N95 component of the primate transient PERG showed spatial tuning, with a peak between 0.14 and 0.28cpd. This spatial tuning was not as apparent for the P50 component. A linear relationship between P50 and N95 amplitude was found with contrast and mean luminance. Both components were attenuated with the introduction of +2 diopters or more of defocus. The inter-session COV for the P50 and N95 components were 23.8 and 19.2%, respectively, while the LOA were 58 and 46%, respectively. The N95:P50 ratio had smaller inter-session variability, was robust to changes in contrast, mean luminance and defocus, and was effective for characterization of inner-retinal dysfunction after pharmacologic block.

Animals↗

PubMed2003

Effect of nitric oxide on excitatory amino acid-evoked discharge of neurons in NTS.

N-methyl-d-aspartate (NMDA) and non-NMDA excitatory amino acid (EAA) receptor subtypes are involved in the integration of visceral afferent inputs within the nucleus of the solitary tract (NTS). Microinjection studies indicate interactions between nitric oxide (NO) and EAA receptors within the NTS. To examine these interactions at the single cell level, this study characterized the effects of the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) and the NO donor 3-[2-hydroxy-2-nitroso-1-propylhydrazino]-1-propanamine (PAPA-NONOate) on the excitatory responses of vagus nerve (VN)-evoked NTS neurons to the activation of (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors in rats. Iontophoresis of l-NAME did not alter spontaneous or VN-evoked discharges, but significantly decreased the number of action potentials (APs) evoked by iontophoretic application of AMPA. The effects of l-NAME on NMDA-evoked discharge were variable; for the population, l-NAME did not change the number of APs evoked by NMDA. PAPA-NONOate enhanced the spontaneous discharge and the number of APs elicited by AMPA but not NMDA. Iontophoresis of the inactive enantiomers N(G)-nitro-d-arginine methyl ester and hydroxydiazenesulfonic acid 1-oxide disodium salt had no effect on AMPA-evoked discharge. Our data suggest that NO facilitates AMPA-mediated neuronal transmission within the NTS.

Action Potentials↗

PubMed1996

Thyrotropin-releasing hormone facilitates spinal nociceptive responses by potentiating NMDA receptor-mediated transmission.

The interaction of thyrotropin-releasing hormone (TRH) with NMDA receptor-mediated responses has been investigated in alpha-chloralose-anaesthetized spinalized rats with respect to its relevance to spinal nociceptive transmission. The effects of TRH and of the uncompetitive NMDA antagonist ketamine were tested on responses of dorsal horn wide dynamic range neurones to noxious pinch, heat and electrical stimuli in parallel with those to iontophoretically applied N-methyl-D-aspartate (NMDA) and AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid). Tests with NMDA blocking doses of ketamine (4 mg/kg i.v.) demonstrated a variable NMDA receptor-mediated component of all synaptic responses. TRH (0.5-1 mg/kg i.v.) enhanced the responses to NMDA (but not AMPA) in parallel with an increase of responses to all noxious stimuli and the 'wind-up' component of the responses to repeated electrical stimulation. This potentiation was completely reversed by a subsequent administration of ketamine (4 mg/kg i.v.). The results indicate that TRH facilitates nociceptive transmission in the spinal dorsal horn via a selective positive modulation of NMDA receptor-mediated transmission.

Analysis of Variance↗

PubMed1996

Influence of methyl parathion on gametogenic and acetylcholinesterase activity in the testis of whitethroated munia (Lonchura malabarica).

Adult male whitethroated munias, Lonchura malabarica (Aves; Passeriformes), were orally administered with methyl parathion (O, O-dimethyl O-(4-nitrophenyl) phosphorothioate), an extensively used organophosphate pesticide, in graded sublethal dose (5 micro g-, or 10 micro g-, or 20 micro g/100 g body wt/day) for variable durations (1-, 5-, or 10 day/s) during their peak reproductive activities in an annual gonadal cycle. No subtle changes in the feeding behavior, mobility, and body weight were noted between the control and different groups of pesticide-fed birds. As a result of the treatment, the paired testicular weight became reduced significantly only after 10 days at 10 micro g and 20 micro g dose levels, but significant decrease in the number of tubules containing healthy germ cells occurred even after single administration of methyl parathion (MP) at the lowest dose (5 micro g/100 g). With the increase in dose and progress of treatment, the number of tubules with healthy germ cells became gradually decreased. The activity of acetylcholinesterase (AChE) in both the brain and testes of MP-treated birds was inhibited in a dose and duration dependent manner. A significant negative correlation was observed between the number of tubules containing degenerated germ cells in the testis and the AChE activity in both the brain and testes of MP-administered birds. However, no remarkable changes in the cytomorphological features, including the nuclear diameter of Leydig cells, were noted in any testis of the pesticide-treated munias. The results of the present investigation suggest that methyl parathion ingestion is harmful to male gametogenic functions in the studied passeriform bird, and the given pesticide may exert its antigonadal effect by impairing cholinergic functions of the brain and/or testes.

Acetylcholinesterase↗

PubMed1981

Variable assimilation of carbon compounds by Candida albicans.

A total of 215 typical strains of Candida albicans were studied for their ability to assimilate 11 carbon compounds. All isolates assimilated lactic acid, ribitol, succinic acid, methyl alpha-D-glucopyranoside. None of the isolates assimilated cellobiose and salicin; 1.9% of the isolates assimilated L-arabinose. Citric acid, glycerol, and L-sorbose were assimilated by greater than 97% of the isolates, whereas melezitose was assimilated by 81% of the isolates. Assimilation results depended on duration of incubation, temperature, and methodology.

Candida albicans↗