Effect of long TE on T1 measurement in STEAM progressive saturation experiment.
Explore the source record for details and available documents.
Magnetic Resonance Spectroscopy↗
Biomedical subjects
S J Li
Publications and source records attributed to S J Li.
Brain tumors: localized H-1 MR spectroscopy at 0.5 T.
PURPOSE: To investigate the feasibility of obtaining clinically useful magnetic resonance (MR) spectra at 0.5 T in cerebral lesions. MATERIALS AND METHODS: Single-voxel localized proton MR spectroscopy was performed at 0.5 T in 18 patients (aged 16-73 years) suspected of having cerebral lesions on MR images who subsequently underwent craniotomy and biopsy and in eight volunteers (aged 21-50 years). The metabolite resonances in the MR spectra were stratified according to the histologic diagnosis. MR spectra demonstrated resonances for choline-containing compounds (Cho), creatine and phosphocreatine, glutamine and glutamate, N-acetylaspartate (NAA), myo-inositol, and lactate. RESULTS: In 14 of 15 patients with cerebral tumors, the Cho-NAA ratio was increased and was greater than 1. In three patients with nonneoplastic cerebral lesions, the ratio did not exceed 1. In healthy control subjects, the average ratio was 0.54. CONCLUSION: H-1 MR spectroscopy at 0.5 T provides clinically useful information in patients with cerebral lesions.
Adolescent↗
Inhibition of E2F-mediated transcription by p202.
Many of the antimicrobial, immunomodulatory and cell growth inhibitory activities of the interferons are mediated by interferon-inducible proteins. Earlier we characterized an interferon-inducible murine protein, p202, whose expression in transfected cells inhibits cell proliferation and which can form a complex with retinoblastoma protein (pRb). Here we report that in transfected cells expression of p202 inhibits E2F-stimulated transcription of a reporter gene and of endogenous genes. Inhibition of the transcriptional activity of E2F by p202 does not depend on fully functional pRb and is correlated with inhibition of the sequence-specific DNA binding of E2F. p202 interacts with the transcription factor E2F (E2F-1/DP-1) in vitro and in vivo. Inhibition of E2F activity by p202 may contribute to growth inhibition by the interferons.
Animals↗
Melanocortin antagonists define two distinct pathways of cardiovascular control by alpha- and gamma-melanocyte-stimulating hormones.
Melanocortin peptides and at least two subtypes of melanocortin receptors (MC3-R and MC4-R) are present in brain regions involved in cardiovascular regulation. In urethane-anesthetized rats, unilateral microinjection of alpha-melanocyte-stimulating hormone (MSH) into the medullary dorsal-vagal complex (DVC) causes dose-dependent (125-250 pmol) hypotension and bradycardia, whereas gamma-MSH is less effective. The effects of alpha-MSH are inhibited by microinjection to the same site of the novel MG4-R/MC3-R antagonist SHU9119 (2-100 pmol) but not naloxone (270 pmol), whereas the similar effects of intra-DVC injection of beta-endorphin (1 pmol) are inhibited by naloxone and not by SHU9119. Hypotensive and bradycardic responses to electrical stimulation of the arcuate nucleus also are inhibited by ipsilateral intra-DVC microinjection of SHU9119. gamma-MSH and ACTH(4-10), but not alpha-MSH, elicit dose-dependent (0.1-12.5 nmol) pressor and tachycardic effects, which are much more pronounced after intracarotid than after intravenous administration. The effects of gamma-MSH (1.25 nmol) are not inhibited by the intracarotid injection of SHU9119 (1.25-12.5 nmol) or the novel MC3-R antagonist SHU9005 (1.25-12.5 nmol). We conclude that the hypotension and bradycardia elicited by the release of alpha-MSH from arcuate neurons is mediated by neural melanocortin receptors (MC4-R/MC3-R) located in the DVC, whereas the similar effects of beta-endorphin, a peptide derived from the same precursor, are mediated by opiate receptors at the same site. In contrast, neither MC3-R nor MC4-R is involved in the centrally mediated pressor and tachycardic actions of gamma-MSH, which, likely, are mediated by an as yet unidentified receptor.
Animals↗
alpha-2-Adrenergic activation of proopiomelanocortin-containing neurons in the arcuate nucleus causes opioid-mediated hypotension and bradycardia.
Treatment of rats for 4 days with alpha-methyldopa, 200 mg/kg/day i.p., increases steady state levels of proopiomelanocortin (POMC) mRNA in the mediobasal hypothalamus, as measured by DNA excess solution hybridization. The increase is prevented by parallel treatment with yohimbine, 2 mg/kg/day i.p., but not by naltrexone, 2 mg/kg/day i.p. Treatment with the peripheral vasodilator hydralazine, 2 mg/kg/day, does not affect POMC mRNA levels. In situ hybridization histochemistry with a cRNA probe for POMC indicates that POMC-containing cells are located within the confines of the arcuate nucleus both in control and in alpha-methyldopa-treated rats, and confirms the increase in POMC mRNA in the latter. Microinjection of 2 micrograms of alpha-methylnorepinephrine unilaterally into the arcuate nucleus of urethane-anesthetized rats causes hypotension and bradycardia, which can be inhibited by 200 ng of yohimbine microinjected into the same site, or by 100 ng l-naloxone microinjected into the ipsilateral nucleus tractus solitarii, but not into the arcuate nucleus. These findings are interpreted to indicate that activation of alpha 2-adrenergic receptors located on POMC-containing neurons in the arcuate nucleus causes beta-endorphin release and stimulation of opiate receptors in the NTS, which results in hypotension and bradycardia, and that this mechanism contributes to the hypotensive action of alpha-methyldopa.
Adrenergic alpha-Agonists↗
Grandparents in Taiwan: a three-generational study.
Grandparents in the Republic of China want to remain influential, but social policy has not provided them with education to fulfill their changing role. The performance of grandparents was examined to determine suitable content for an intervention program. A sample of 751 non-consanguineous participants from urban and rural Taiwan included 234 grandparents, 241 parents, and 276 grandchildren. Each generation was administered a separate version of the Grandparent Strengths and Needs Inventory that was translated into Mandarin. Respondents identified favorable qualities of grandparents as well as aspects of their relationships in which growth was necessary. Multivariate analysis of variance, univariate analysis of variance, Scheffé and t-tests were used to analyze scores, confirm results, and facilitate interpretation. All three generations described aspects of grandparent success and specific realms of learning they should acquire to become more effective. Significant main effects that influenced responses about grandparent performance were generation, gender of grandchild, age of grandchild, frequency of grandchild care by grandparent, generations living together, and amount of time grandparent and grandchild spent together. Considerations were recommended to improve behavior of grandparents and guide the development of educational programs for them.
Aged↗
The activity of xenobiotic enzymes and the cytotoxicity of mitoxantrone in MCF 7 human breast cancer cells treated with inducing agents.
This study investigated the effect of inducers on the major enzymes responsible for metabolising the quinone antitumor agent mitoxantrone, and on its cytotoxicity in MCF 7 human breast cancer cells. Four inducers were used: 1,2-benzanthracene (BA), phenobarbitone (PB); rifampicin (R) and dexamethasone (DEX). Of these, BA was the most effective, increasing cytochrome P450 dependent metabolism 64-fold and DT-diaphorase activity 1.6-fold. R did not cause an increase in any of the enzyme activities measured and, in fact inhibited glutathione peroxidase activity. PB and DEX increased NADPH cytochrome c reductase activity but had no effect on either DT-diaphorase or cytochrome P450 dependent activities. BA potentiated the cytotoxicity of mitoxantrone in terms of leakage of lactate dehydrogenase (LDH) activity and loss of reduced glutathione (GSH) and protein from cultures. PB had a smaller potentiating effect on cytotoxicity and DEX had no effect. Studies with the enzyme inhibitors, dicoumarol (inhibits DT-diaphorase) and metyrapone (inhibits cytochrome P450), indicate that at least two reactive species are involved in mitoxantrone cytotoxicity. One intermediate, formed by cytochrome P450, caused LDH leakage and GSH depletion. Formation of the second intermediate was catalysed by DT-diaphorase and this hydroquinone caused loss of intracellular protein and GSH. We propose that autooxidation of the hydroquinone resulting in generation of reactive oxygen species contributes to mitoxantrone cytotoxicity. Concomitant exposure to inducing agents may alter the cytotoxicity associated with many cytotoxic drugs, not just mitoxantrone, and this is an important consideration as many cytotoxics have a narrow therapeutic index.
Benz(a)Anthracenes↗
The DOA pathway: studies on the functions and mechanisms of ubiquitin-dependent protein degradation in the yeast Saccharomyces cerevisiae.
Explore the source record for details and available documents.
Amino Acid Sequence↗
The genes encoding the biotin carboxyl carrier protein and biotin carboxylase subunits of Bacillus subtilis acetyl coenzyme A carboxylase, the first enzyme of fatty acid synthesis.
The genes encoding two subunits of acetyl coenzyme A carboxylase, biotin carboxyl carrier protein, and biotin carboxylase have been cloned from Bacillus subtilis. DNA sequencing and RNA blot hybridization studies indicated that the B. subtilis accB homolog which encodes biotin carboxyl carrier protein, is part of an operon that includes accC, the gene encoding the biotin carboxylase subunit of acetyl coenzyme A carboxylase.
Acetyl-CoA Carboxylase↗
Correlation of radiobiological assays of hypoxic fraction with phosphorus-31 magnetic resonance spectroscopy across multiple tumor lines.
Hypoxic fractions were measured in multiple tumor models and compared to 31P magnetic resonance spectroscopy (MRS) parameters. Hypoxic fractions were measured by excision assays in intramuscular and subcutaneous RIF-1 tumors, large and small SCCVII tumors, and KHT tumors. The hypoxic fractions ranged from 3% (small SCCVII) to 21% (KHT). Measurements of 31P MRS parameters (indices of tumor metabolism) were made under the same conditions used in the hypoxic fraction assays. The PCR/Pi ratios in the five tumor models were strongly correlated (r2 = 0.98, tau = 1.00, P < 0.02) with their hypoxic fractions, and the NTP/Pi ratio was weakly correlated (r2 = 0.67, tau = 0.60, P < 0.17) with hypoxic fraction. Smaller values of the PCr/Pi and NTP/Pi ratios were found in the tumors with larger hypoxic fractions. These experiments indicate that 31P MRS may provide a relative measurement of hypoxic fractions across different tumor lines that can be applied non-invasively to individual tumors.
Animals↗
Body composition of Colombian women.
Measurements of anthropometry and total body water (TBW) were made in 99 women 19-44 y of age living in socioeconomically deprived circumstances in Cali, Colombia. TBW was measured by dilution of deuterium oxide. An empirical equation for estimating lean body mass (LBM) was derived and applied satisfactorily to an independent study group. Comparisons were also made with body-composition values obtained by the Durnin and Womersley equations and an equation derived from rural women living in Guatemala. Neither set of equations was suitable for use with the Colombian subjects because both significantly overestimated LBM and therefore underestimated body fat. Lower values of standing height in older women suggest that they may have been subjected to more severe undernutrition during their growth than the younger subjects. When compared with a group of US women, Colombian subjects were less physically fit and had greater subcutaneous-fat deposits, which were distributed over the trunk and limbs, whereas body mass indexes and waist-hip ratios were not significantly different.
Adipose Tissue↗
Serotonin alters an inwardly rectifying current (Ih) in rat cerebellar Purkinje cells under voltage clamp.
The effects of serotonin (5-HT) on the hyperpolarization-activated sodium-potassium inward current (H-current: Ih) were examined in cerebellar Purkinje cells (PCs) under current- and voltage-clamp conditions. Quasi-steady state current versus voltage relationships under voltage clamp conditions showed that 5-HT decreased the inward rectification at potentials negative to -70 mV with a corresponding decrease in the slope conductance. In 70% of PCs, 5-HT produced dose-related attenuations of the Ih current with corresponding decreases in slope conductances across a range of hyperpolarized potentials. A negative shift in the Ih activation curve was elicited by 5-HT so that the amplitude of Ih current active near rest and at more hyperpolarized ranges was decreased. Serotonin-induced inhibition of Ih shows some receptor subtype selectivity in that DOI, the 5-HT2/IC receptor agonist, most closely mimicked the actions of 5-HT. This study reveals a novel inhibitory action of 5-HT on Ih in cerebellar Purkinje cells which may contribute to direct inhibitory effects of 5-HT on spontaneous firing and modulatory actions on gamma-aminobutyric acid (GABA)-mediated responses to PCs.
Animals↗
Blood-feeding of the gerbil flea Nosopsyllus laeviceps kuzenkovi (Yagubyants), vector of plague in Inner Mongolia, China.
The gerbil flea Nosopsyllus laeviceps (Wagner) (Siphonaptera: Ceratophyllidae) is an important Palaearctic vector of enzootic plague among sylvan and campestral rodents. Laboratory blood-feeding experiments with the subspecies N.l.kuzenkovi (Yagubyants) from Inner Mongolia, China, using three rodent species including the natural host Meriones unguiculatus (Milne-Edwards), demonstrated a positive relationship between per cent feeding and time allowed for feeding, particularly for female fleas. Also the bloodmeal size was proportional to sucking time and was significantly greater in females, which are larger, than in males. However, on all four strains of host tested, there was no significant correlation between the feeding success rate of the fleas and the amount of blood they imbibed. Fleas fed better on active compared to confined M.unguiculatus. These findings agree with studies of other flea species.
Animals↗
Growth rate regulation of Escherichia coli acetyl coenzyme A carboxylase, which catalyzes the first committed step of lipid biosynthesis.
Acetyl coenzyme A (CoA) carboxylase catalyzes the synthesis of malonyl-CoA, the first intermediate of fatty acid synthesis. The Escherichia coli enzyme is encoded by four subunits located at three different positions on the E. coli chromosome. The accBC genes lie in a small operon at min 72, whereas accA and accD are located at min 4.3 and 50, respectively. We examined the expression of the genes that encode the E. coli acetyl-CoA carboxylase subunits (accA, accBC, and accD) under a variety of growth conditions by quantitative Northern (RNA) blot analysis. We found a direct correlation between the levels of transcription of the acc genes and the rate of cellular growth. Consistent results were also obtained upon nutritional upshift and downshift experiments and upon dilution of stationary-phase cultures into fresh media. We also determined the 5' end of the accA and accD mRNAs by primer extension and did transcriptional fusion analysis of the previously reported accBC promoter. Several interesting features were found in the promoter regions of these genes, including a bent DNA sequence and an open reading frame within the unusually long leader mRNA of the accBC operon, potential stem-loop structures in the accA and accD mRNA leader regions, and a stretch of GC-rich sequences followed by AT-rich sequences common to all three promoters. In addition, both accA and accD are located in complex gene clusters. For example, the accA promoter was localized within the upstream polC gene (which encodes the DNA polymerase III catalytic subunit), suggesting that additional regulatory mechanisms exist.
Acetyl-CoA Carboxylase↗
The genes encoding the two carboxyltransferase subunits of Escherichia coli acetyl-CoA carboxylase.
We report characterization of the component proteins and molecular cloning of the genes encoding the two subunits of the carboxyltransferase component of the Escherichia coli acetyl-CoA carboxylase. Peptide mapping of the purified enzyme component indicates that the carboxyltransferase component is a complex of two nonidentical subunits, a 35-kDa alpha subunit and a 33-kDa beta subunit. The alpha subunit gene encodes a protein of 319 residues and is located immediately downstream of the polC gene (min 4.3 of the E. coli genetic map). The deduced amino acid composition, molecular mass, and amino acid sequence match those determined for the purified alpha subunit. Six sequenced internal peptides also match the deduced sequence. The amino-terminal sequence of the beta subunit was found within a previously identified open reading frame of unknown function called dedB and usg (min 50 of the E. coli genetic map) which encodes a protein of 304 residues. Comparative peptide mapping also indicates that the dedB/usg gene encodes the beta subunit. Moreover, the deduced molecular mass and amino acid composition of the dedB/usg-encoded protein closely match those determined for the beta subunit. The deduced amino acid sequences of alpha and beta subunits show marked sequence similarities to the COOH-terminal half and the NH2-terminal halves, respectively, of the rat propionyl-CoA carboxylase, a biotin-dependent carboxylase that catalyzes a similar carboxyltransferase reaction reaction. Several conserved regions which may function as CoA-binding sites are noted.
Acetyl-CoA Carboxylase↗
The gene encoding the biotin carboxylase subunit of Escherichia coli acetyl-CoA carboxylase.
We report the molecular cloning and DNA sequence of the gene encoding the biotin carboxylase subunit of Escherichia coli acetyl-CoA carboxylase. The biotin carboxylase gene encodes a protein of 449 residues that is strikingly similar to amino-terminal segments of two biotin-dependent carboxylase proteins, yeast pyruvate carboxylase and the alpha-subunit of rat propionyl-CoA carboxylase. The deduced biotin carboxylase sequence contains a consensus ATP binding site and a cysteine-containing sequence preserved in all sequenced bicarbonate-dependent biotin carboxylases that may play a key catalytic role. The gene encoding the biotin carboxyl carrier protein (BCCP) subunit of acetyl-CoA carboxylase is located upstream of the biotin carboxylase gene and the two genes are cotranscribed. As previously reported by others, the BCCP sequence encoded a protein of 16,688 molecular mass. However, this value is much smaller than that (22,500 daltons) obtained by analysis of the protein. Amino-terminal amino acid sequencing of the purified BCCP protein confirmed the deduced amino acid sequence indicating that BCCP is a protein of atypical physical properties. Northern and primer extension analyses demonstrate that BCCP and biotin carboxylase are transcribed as a single mRNA species that contains an unusually long untranslated leader preceding the BCCP gene. We have also determined the mutational alteration in a previously isolated acetyl-CoA carboxylase (fabE) mutant and show the lesion maps within the BCCP gene and results in a BCCP species defective in acceptance of biotin. Translational fusions of the carboxyl-terminal 110 or 84 (but not 76) amino acids of BCCP to beta-galactosidase resulted in biotinated beta-galactosidase molecules and production of one such fusion was shown to result in derepression of the biotin biosynthetic operon.
Acetyl-CoA Carboxylase↗
Effects of local irradiation on spin-lattice relaxation time of phosphate metabolites in mouse tumors monitored by 31P magnetic resonance spectroscopy.
An inversion-recovery pulse sequence and solenoidal surface coil were employed to determine the spin-lattice relaxation time (T1) in murine tumors (RIF-1 and SCCVII). Reduction in T1s of inorganic phosphate (Pi) and nucleotide triphosphates (NTP) has been observed in irradiated tumors compared with unirradiated tumors. The reduction is accompanied by tumor regression and improved tumor energetic status in both tumor lines. The results of the T1 measurement of phosphate metabolites in tumors suggest that partial saturation effects may exist in spectra and could effect quantitative analysis when short repetition time is used. The reduction in T1s of Pi and NTP may be attributed to the active biochemical exchange and better tumor oxygenation in irradiated tumors.
Animals↗
Determination of absolute phosphate metabolite concentrations in RIF-1 tumors in vivo by 31P-1H-2H NMR spectroscopy using water as an internal intensity reference.
The absolute metabolite quantification method of Thulborn and Ackerman [J. Magn. Reson. 55, 357 (1983)] in which the tissue water proton signal is used as an internal intensity standard and its more recent variation in which NMR peak intensities are referenced to that of the natural abundance deuterium signal of water [Li et al., SMRM Abstr. 2, 825 (1988); Song et al., Magn. Reson. Med. 25, 45 (1992) have been implemented to obtain absolute phosphate metabolite concentrations in subcutaneous RIF-1 tumors during untreated growth and following treatment with 5-fluorouracil. The equivalence of these two hydrogen isotopes as intensity standards and the validity of their use in the determination of absolute metabolite concentrations in vivo by NMR has been demonstrated. On matched in vivo and extract tumor samples (n = 5), excellent agreement has been obtained between nucleoside triphosphate concentrations determined by NMR and those derived by HPLC analysis for the control tumors. Following 3 days of untreated growth, absolute concentrations of phosphate metabolites in RIF-1 tumors (n = 10) decreased significantly, except for the Pi concentration which did not vary. For the treated tumors (n = 10) there were no changes in metabolite concentrations except for a decrease in the PCr and, possibly, Pi concentrations. The PCr/Pi ratio in the latter tumors did not change. These observations suggest that changes in absolute metabolite concentrations may be more sensitive indices of response to therapy than changes in metabolite peak amplitude ratios, a parameter commonly used to express in vivo NMR data.
Animals↗