Gene/Protein Disease Symptom Drug Enzyme Compound
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Overall, there is a wide range of programs offered at the community level. Most of the group cessation clinics, both nonprofit and commercial, typically offer group support, behavior modification, and stress and weight management, with similar emphases in their companion self-help manuals. It often is difficult to distinguish between the various methods employed by the diverse programs, with those that offer maintenance and relapse prevention components faring the best. In general, the multiple-component programs, whether group or self-help packages, seem to hold the most promise for achieving and maintaining abstinence; however, there is some evidence that overwhelming the smoker with too many new behaviors and skills lowers the effectiveness of otherwise successful components. The challenges for community-based programs will be to modify and adapt their materials and sessions to address the needs uncovered in the recent emphasis on the process of smoking cessation. Specifically, program content must address the issue of recycling and relapse prevention. Smokers who have made unsuccessful quit attempts must be able to reframe those attempts in a positive manner, so that they are motivated to try again. Similarly, recent quitters need the skills and motivation to remain abstinent. Although some cessation programs allow clients to participate in future sessions or meetings for little or no extra cost, few have any strategies for dealing with long-term maintenance. As community-based programs incorporate these elements of cessation, quit rates are likely to increase. An additional challenge is found in the difficulty of reaching the hard-core, heavy smoker. There is little doubt that light-to-moderate smokers find it easier to achieve long-term cessation. Cessation programs that motivate heavy smokers to attempt to quit or that include adjunct therapies to assist the heavy smoker (i.e., nicotine gum) to quit smoking are likely to be positively received. Currently, however, efforts specifically designed to assist heavy smokers are experimental. A final challenge is to adapt materials and sessions to motivate and assist the hard-to-reach smokers. Increasingly, smoking is becoming a habit of individuals in lower socioeconomic groups, including minorities, non-high school graduates, and young women. Avenues that have been used to reach white middle-class Americans are not easily transferred to such groups. Some attention is already being paid to development of more culturally appropriate materials (e.g., the ALA Manual oriented to blue collar workers and the ACS focus on pregnant women); however, it remains a challenge to motivate members of these groups to participate in smoking cessation activities.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Community-based programs for smoking cessation. 174 95

1. Mammary-tissue biopsies were obtained from multiparous cows at 30 and 7 days pre partum and 7 and 40 days post partum. Investigations of the effect of lactogenesis on fatty acid and lactose synthesis involved measurements of biosynthetic capacity (tissue-slice incubations in vitro) and activities of relevant enzymes. 2. Fatty acid synthesis from acetate increased over 20-fold from 30 days pre partum to 40 days post partum. Changes in the lipogenic capacity of mammary-tissue slices more closely paralleled increases in the activities of acetyl-CoA carboxylase (EC 6.4.1.2) and acetyl-CoA synthetase (EC 6.2.1.1) than of other enzymes involved in acetate incorporation into fatty acids or in NADPH generation. 3. Lactose biosynthesis by mammary-tissue slices, lactose synthetase activity (EC 2.4.1.22) and alpha-lactalbumin concentration were all negligible at 30 days pre partum but increased 2.5-4-fold between 7 days pre partum and 40 days post partum. Phosphoglucomutase (EC 2.7.5.1), UDP-glucose pyrophosphorylase (EC 2.7.7.9) and UDP-glucose 4-epimerase (EC 5.1.3.2) had substantial activities at 30 days pre partum and increased less dramatically during lactogenesis. 4. Results are consistent with acetyl-CoA carboxylase and perhaps acetyl-CoA synthetase representing the regulatory enzyme(s) in fatty acid synthesis, with lactose synthetase (alpha-lactalbumin) serving a similar function in lactose biosynthesis.
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PMID:Metabolic adaptations during lactogenesis. Fatty acid and lactose synthesis in cow mammary tissue. 414 47

The LEEP Program at the SRHS has completed its first year. Executing the strategic action plans could not have been accomplished without the collaboration of multiple agencies-the ACS, ALA, DHEC, SADAC, and the SRHS. Activities surrounding education, awareness, and the development of support programs during this year have moved us closer to achieving our goal-to develop and implement a systematic educational program including a collaborative community-wide smoking cessation initiative. We had many successes during the first year of the LEEP program. However, future opportunities remain. Offering Freshstart facilitator class twice a year will provide trained facilitators for the every-other-month Freshstart classes at the Gibbs Regional Cancer Center and community smoking cessation classes as needed. Moreover, smokers in the community can attend a smoking cessation support group that began in January 2002. The support group reinforces the safety net of services developed within the first year. Collaboration with other community organizations ensure that continued efforts are made to improve the health and quality-of-life for upstate South Carolina residents. "According to results from the 1994 National Health Interview Supplement (NHIS-2000), 70% of smokers indicated a strong desire to quit" (Westmaas, 2000). It is the role and responsibility of health care institutions to provide the safety net of services to enable patients and the community at large to be successful in their efforts to kick the cigarette habit.
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PMID:Community outreach: providing a comprehensive approach to smoking cessation. 1238 96

Broadly applicable strategies facilitating direct and selective modulation of the intracellular levels of physiologically important small molecules are essential for dissecting their integral and multiple roles in cellular processes. Therefore, we have been exploring the suitability of RNA aptamers for this purpose. Using the Escherichia coli heme biosynthetic pathway as a simple model of a negative feedback regulated process, we show that heme-binding RNA aptamers, developed in vitro and expressed intracellularly, induce a heme-dependent growth defect in an E. coli heme auxotroph defective in converting delta-aminolevulinic (delta-ALA) acid into downstream products. Relative to a control oligonucleotide, the aptamers also induce delta-ALA accumulation in cells grown under heme-limiting conditions. Increasing the concentration of heme in the media completely reverses both the growth defect and delta-ALA accumulation, except for two aptamers for which reversal is partial. Thus, these aptamers specifically target their cognate ligand in vivo and functionally modulate its intracellular concentration, demonstrating that RNA aptamers are useful tools for elucidating the role of heme and possibly other small molecules in regulating cellular networks.
ACS Chem Biol 2006 Sep 19
PMID:Utilizing RNA aptamers to probe a physiologically important heme-regulated cellular network. 1716 39

We have developed a method for dissecting single neurons from the nematode Ascaris suum, in order to determine their peptide content by mass spectrometry (MS). In this paper, we use MALDI-TOF MS and tandem MS to enumerate and sequence the peptides present in the two neurons, ALA and RID, that comprise the dorsal ganglion. We compare the peptide content determined by MS with the results of immunocytochemistry and in situ hybridization of previously isolated peptides AF2, AF8 and 6 peptides encoded by the afp-1 transcript. We find complete agreement between the three techniques, which validates single neuron MS as a method for peptide localization. We also discovered and sequenced 6 novel peptides in the ALA neuron. Cloning of cDNAs and database searching of Genomic Survey Sequences showed that transcript afp-12 encodes peptide AF36 (VPSAADMMIRFamide), and afp-13 encodes AF19 (AEGLSSPLIRFamide), AF34 (DSKLMDPLIRFamide), AF35 (DPQQRIVTDETVLRFamide), and 3 non-amidated peptides (PepTT, PepTL, and PepGE). We have found no similarities with reported peptide expression in the nematode Caenorhabditis elegans. This method promises to be ideally suited for determining the peptide content of each of the 298 neurons in the nervous system of this nematode.
ACS Chem Neurosci 2010 Jul 21
PMID:Mapping neuropeptide expression by mass spectrometry in single dissected identified neurons from the dorsal ganglion of the nematode Ascaris suum. 2080 53

We utilized three independent techniques, immunocytochemistry (ICC), single cell mass spectrometry (MS), and in situ hybridization (ISH), to localize neuropeptides and their transcripts in the nervous system of the nematode Ascaris suum . AF11 (SDIGISEPNFLRFa) is an endogenous peptide with potent paralytic effects on A. suum locomotory behavior. A highly specific antibody to AF11 showed robust immunostaining for AF11 in the paired AVK neurons in the ventral ganglion. We traced the processes from the AVK neurons into the ventral nerve cord and identified them as ventral cord interneurons. MS and MS/MS of single dissected AVKs detected AF11, two previously characterized peptides (AF25 and AF26), seven novel sequence-related peptides, including several sharing a PNFLRFamide C-terminus, and peptide NY, a peptide with an unrelated sequence. Also present in a subset of AVKs was AF2, a peptide encoded by the afp-4 transcript. By sequencing the afp-11 transcript, we discovered that it encodes AF11, all the AF11-related peptides detected by MS in AVK, and peptide NY. ISH detected the afp-11 transcript in AVK neurons, consistent with other techniques. ISH did not detect afp-11 in the ALA neuron, although both ICC and MS found AF11 in ca. 30% of ALAs. All 10 AF11-related peptides reduced acetylcholine-induced muscle contraction, but they differed in their rate of reversal of inhibition after removal of the peptide.
ACS Chem Neurosci 2013 Mar 20
PMID:Three independent techniques localize expression of transcript afp-11 and its bioactive peptide products to the paired AVK neurons in Ascaris suum: in situ hybridization, immunocytochemistry, and single cell mass spectrometry. 2350 78

Surgical resection, one of the main clinical treatments of intracranial glioblastoma, bears the potential risk of incomplete excision due to the inherent infiltrative character of the glioblastoma. To maximize the accuracy of surgical resection, the magnetic resonance (MR) and fluorescence imaging are widely used for the tumor preoperative diagnosis and intraoperative positioning. However, present commercial MR contrast agents and fluorescent dyes can only function for single mode of imaging and are subject to poor blood-brain barrier (BBB) permeability and nontargeting-specificity, resulting in the apparent risks of inefficient diagnosis and resection of glioblastoma. Considering the unique MR/upconversion luminescence (UCL) bimodal imaging feature of upconversion nanoparticles (UCNPs), herein, we have developed a dual-targeting nanoprobe (ANG/PEG-UCNPs) to cross the BBB, target the glioblastoma, and then function as a simultaneous MR/NIR-to-NIR UCL bimodal imaging agent, which showed a much enhanced imaging performance in comparison with the clinically used single MRI contrast (Gd-DTPA) and fluorescent dye (5-ALA). Moreover, their biocompatibility, especially to brains, was systematically assessed by the histological/hematological examination, indicating a negligible in vivo toxicity. As a proof-of-concept, the ANG/PEG-UCNPs hold the great potential in MR diagnosis and fluorescence positioning of glioblastoma for the efficient tumor surgery.
ACS Nano 2014 Feb 25
PMID:Dual-targeting upconversion nanoprobes across the blood-brain barrier for magnetic resonance/fluorescence imaging of intracranial glioblastoma. 2439 30

5-Aminolevulinic acid (5-ALA) is a precursor of a strong photosensitizer, protoporphyrin IX (PphIX), for photodynamic therapy (PDT). Developing appropriate delivery carriers that can assist 5-ALA in bypassing the lipophilic barrier to directly enter into cancer cells is a research focus. The improved delivery of 5-ALA is even important for skin cancer therapy through PDT process. In this work, targeting ligand folic acid (FA)-functionalized hollow mesoporous silica nanoparticles (HMSNPs) were fabricated to deliver 5-ALA for PDT against B16F10 skin cancer cells. The FA targeting ligand enabled selective endocytosis of 5-ALA loaded HMSNPs into cancer cells. PphIX formed from delivered 5-ALA exhibited high photocytotoxicity to the cancer cells in vitro.
ACS Appl Mater Interfaces 2015 May 27
PMID:Targeted delivery of 5-aminolevulinic acid by multifunctional hollow mesoporous silica nanoparticles for photodynamic skin cancer therapy. 2597 79

The endogenous amino acid, 5-aminolevulinic acid (5-ALA), has received significant attention as an imaging agent, including ongoing clinical trials for image-guided tumor resection due to its selective uptake and subsequent accumulation of the fluorescent protoporphyrin IX in tumor cells. Based on the widely reported selectivity of 5-ALA, a new positron emission tomography imaging probe was developed by reacting methyl 5-bromolevulinate with [13N] ammonia. The radiotracer, [13N] 5-ALA, was produced in high radiochemical yield (65%) in 10 min and could be purified using only solid phase cartridges. In vivo testing in rats bearing intracranial 9L glioblastoma showed peak tumor uptake occurred within 10 min of radiotracer administration. Immunohistochemical staining and fluorescent imaging was used to confirm the tumor location and accumulation of the tracer seen from the PET images. The quick synthesis and rapid tumor specific uptake of [13N] 5-ALA makes it a potential novel clinical applicable radiotracer for detecting and monitoring tumors noninvasively.
ACS Med Chem Lett 2017 Dec 14
PMID:Radiochemical Synthesis and Evaluation of 13N-Labeled 5-Aminolevulinic Acid for PET Imaging of Gliomas. 2925 40

Herein, we present the fabrication of dispersed, 5.0 wt % (1.74 vol %) Ti3C2Tz MXene epoxy nanocomposites (NCs), and report on their water transport and mechanical properties. To make the composites, Li+ ions between Ti3C2Tz MXene multilayers, MLs, present after the etching step were exchanged with either 12-aminolauric acid, ALA, or di(hydrogenated tallow)benzyl methyl ammonium chloride, DHT. After drying, the resulting ML powders were added at room temperature to the epoxy resin (diglycidyl ether of bisphenol A), followed by the curing agent, triethylenetetramine. The NCs were characterized by X-ray diffraction, thermogravimetric analysis, dynamic vapor sorption, dynamic mechanical analysis, scanning and transmission electron microscopies, and infrared spectroscopy. From XRD, the lack of signature MXene basal peaks, as well as evidence of exfoliation supported by TEM micrographs, we conclude that the MXene ML had indeed been intercalated by the epoxy. The distribution of the exfoliated multilayers, MLs, however, was not uniform. Nevertheless, our relative permeabilities, with a 1.74 vol % loading, are 5 times lower than results obtained in the carbon- or clay-reinforced epoxy NC literature. The lower permeabilities are due to reductions in both solubilities and diffusivities relative to the neat polymer. In the case of DHT, the water solubility at all temperatures was almost halved. The mechanical properties and thermal stability are found to be slightly improved with the addition of DHT-MXene. As far as we are aware, this is the first report of exfoliation of MXene in an epoxy matrix. Additionally, this study is the first to measure the diffusion of water in MXene epoxy NCs. More work on better dispersion of the MLs is indicated and ongoing.
ACS Appl Mater Interfaces 2019 Oct 23
PMID:Water Transport and Thermomechanical Properties of Ti3C2Tz MXene Epoxy Nanocomposites. 3153 21


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