Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human cytomegalovirus (HCMV) DNA was digested with restriction endonucleases and the fragments characterized with respect to molecular weight and relative mole proportions. The terminal fragments were identified by digesting HCMV DNA with exonucleases before restriction endonuclease treatment and subsequent gel analysis. The HindIII fragments of HCMV DNA were cloned in Escherichia coli and recombinant plasmids were characterized by digestion with restriction endonucleases and by molecular hybridization with HindIII, Bg/II and XbaI fragments of the virus genome. Data from these experiments were used to construct physical maps of HCMV DNA for the HindIII, Bg/II and XbaI restriction endonucleases. The terminal regions of the genome and the region containing fragment HindIII M were shown to be heterogeneous.
J Gen Virol 1982 Mar
PMID:Use of recombinant plasmids to investigate the structure of the human cytomegalovirus genome. 627 70

The effects of external anions on gating of Na channels of frog skeletal muscle were studied under voltage clamp. Anions reversibly shift the voltage dependence of peak sodium permeability and of steady state sodium inactivation towards more negative potentials in the sequence: methanesulfonate less than or equal to Cl- less than or equal to acetate less than Br- less than or equal to NO-3 less than or equal to SO2-4 less than benzenesulfonate less than SCN- less than ClO-4; approximately the lyotropic sequence. Voltage shifts are graded with mole fraction in mixtures and are roughly additive to calcium shifts. The peak PNa is not greatly affected. Except for SO2-4, these anions did not change the Ca++ activity of the solutions as measured with the dye murexide. Shifts of gating can be explained as the electrostatic effect of anion adsorption to the Na channel or to nearby lipid. Such adsorption is expected to follow the lyotropic series. Anions also interfere significantly with the response of a Ca-sensitive membrane electrode following the same sequence of effectiveness as the shifts of gating. The lyotropic anions decrease the Ca++ sensitivity and cause anomalously negative responses of the Ca electrode because these anions are somewhat permeant in the hydrophobic detector membrane.
J Gen Physiol 1983 Feb
PMID:Lyotropic anions. Na channel gating and Ca electrode response. 630 98

The present study compares and quantitates both solvent drag and solute drag forces in a system with both heteropore and homopore membranes. It is shown that tracer solute permeability can be increased if solution flow or driver solute flux is in the direction of tracer diffusion. Either force can decrease tracer permeability if the force can decrease tracer permeability if the force is opposite to the direction of tracer diffusion. The two forces can be additive or one force may reduce the effect of the other force. In the particular system quantitated, solute drag is shown to be some 300 times more effective than solvent drag on a mole-to-mole basis. The use of a number of solute pairs on other homopore and heteropore membranes confirms the finding that the two drag forces can be analyzed or manipulated in a variety of systems.
J Gen Physiol 1982 Mar
PMID:Effects of solvent and solute drag on transmembrane diffusion. 680 95

N-methyl-D-aspartate (NMDA) receptor channels in cultured CA1 hippocampal neurons were studied using patch-clamp techniques. The purpose of the research was to determine the occupancy of the channel by permeant cations and to determine the influence of charged residues in or near the pore. The concentration dependence of permeability ratios, the mole-fraction dependence of permeability ratios, the concentration dependence of the single-channel conductance, and a single-channel analysis of Mg2+ block all independently indicated that the NMDA receptor behaves as a singly-occupied channel. More precisely, there is one permeant cation at a time occupying the site or sites that are in the narrow region of the pore directly in the permeation pathway. Permeability-ratio measurements in mixtures of monovalent and divalent cations indicated that local charges in or near the pore do not produce a large local surface potential in physiologic solutions. In low ionic strength solutions, a local negative surface potential does influence the ionic environment near the pore, but in normal physiologic solutions the surface potential appears too small to significantly influence ion permeation. The results indicate that the mechanism for the high Ca2+ conductance of the NMDA receptor channel is not the same as for the voltage-dependent Ca2+ channel (VDCC). The VDCC has two high affinity, interacting binding sites that provide high Ca2+ selectivity and conductance. The binding site of the NMDA receptor is of lower affinity. Therefore, the selectivity for Ca2+ is not as high, but the lower affinity of binding provides a faster off rate so that interacting sites are not required for high conductance.
J Gen Physiol 1994 Feb
PMID:Ionic permeability characteristics of the N-methyl-D-aspartate receptor channel. 751 45

Naked mole-rats have no access to obvious sources of vitamin D and therefore have an impoverished vitamin D status. In an investigation into the effects of vitamin D supplementation, inadvertently supraphysiological doses of 130,000 times the normal dose of vitamin D were administered. Within 5 days animals appeared lethargic, with reduced food intake. All but one of the seven animals were killed and blood was collected. Plasma vitamin D metabolites 25(OH)D and 1,25(OH)2D and calcium were determined. Both vitamin D metabolite concentrations exceeded the upper limits of sensitivity of the assays (> 100 ng/ml 25(OH)D and > 210 pg/ml 1,25(OH)2D). Active calcium uptake in the intestine was evident along with concomitant increases in calcium concentration in plasma, bone, and teeth. The remaining animal survived, but showed scab-like formations in the skin around the lower jaw and along the nipple line. X-ray analyses revealed calcium deposition in these cornified regions, although there was no evidence of metastatic calcification in other tissues. Deposition of excess calcium in skin that is regularly sloughed off and in teeth that are continuously worn down and replaced may reduce the vitamin D-induced hypercalcaemia and thus alleviate the effects of vitamin D intoxication.
Gen Comp Endocrinol 1995 Jul
PMID:Vitamin D3 intoxication in naked mole-rats (Heterocephalus glaber) leads to hypercalcaemia and increased calcium deposition in teeth with evidence of abnormal skin calcification. 765 55

In whole-cell patch clamp recordings from chick dorsal root ganglion neurons, removal of intracellular K+ resulted in the appearance of a large, voltage-dependent inward tail current (Icat). Icat was not Ca2+ dependent and was not blocked by Cd2+, but was blocked by Ba2+. The reversal potential for Icat shifted with the Nernst potential for [Na+]. The channel responsible for Icat had a cation permeability sequence of Na+ >> Li+ >> TMA+ > NMG+ (PX/PNa = 1:0.33:0.1:0) and was impermeable to Cl-. Addition of high intracellular concentrations of K+, Cs+, or Rb+ prevented the occurrence of Icat. Inhibition of Icat by intracellular K+ was voltage dependent, with an IC50 that ranged from 3.0-8.9 mM at membrane potentials between -50 and -110 mV. This voltage-dependent shift in IC50 (e-fold per 52 mV) is consistent with a single cation binding site approximately 50% of the distance into the membrane field. Icat displayed anomolous mole fraction behavior with respect to Na+ and K+; Icat was inhibited by 5 mM extracellular K+ in the presence of 160 mM Na+ and potentiated by equimolar substitution of 80 mM K+ for Na+. The percent inhibition produced by both extracellular and intracellular K+ at 5 mM was identical. Reversal potential measurements revealed that K+ was 65-105 times more permeant than Na+ through the Icat channel. Icat exhibited the same voltage and time dependence of inactivation, the same voltage dependence of activation, and the same macroscopic conductance as the delayed rectifier K+ current in these neurons. We conclude that Icat is a Na+ current that passes through a delayed rectifier K+ channel when intracellular K+ is reduced to below 30 mM. At intracellular K+ concentrations between 1 and 30 mM, PK/PNa remained constant while the conductance at -50 mV varied from 80 to 0% of maximum. These data suggest that the high selectivity of these channels for K+ over Na+ is due to the inability of Na+ to compete with K+ for an intracellular binding site, rather than a barrier that excludes Na+ from entry into the channel or a barrier such as a selectivity filter that prevents Na+ ions from passing through the channel.
J Gen Physiol 1994 Oct
PMID:Permeation of Na+ through a delayed rectifier K+ channel in chick dorsal root ganglion neurons. 783 40

Limited proteolysis of intact yeast methionine aminopeptidase (MAP1) with trypsin releases a 34 kDa fragment whose NH2-terminal sequence begins at Asp70, immediately following Lys69. These results suggest that yeast MAP may have a two-domain structure consisting of an NH2-terminal zinc finger domain and a C-terminal catalytic domain. To test this, a mutant MAP lacking residues 2-69 was generated, overexpressed, purified and analyzed. Metal ion analyses indicate that 1 mol of wild-type yeast MAP contains 2 mol of zinc ions and at least 1 mol of cobalt ion, whereas 1 mol of the truncated MAP lacking the putative zinc fingers contains only a trace amount of zinc ions but still contains one mole of cobalt ion. These results suggest that the two zinc ions observed in the native yeast MAP are located at the Cys/His rich region and the cobalt ion is located in the catalytic domain. The kcat and Km values of the purified truncated MAP are similar to those of the wild-type MAP when measured with peptide substrates in vitro and it appears to be as active as the wild-type MAP in vivo. However, the truncated MAP is significantly less effective in rescuing the slow growth phenotype of map mutant than the wild-type MAP. These findings suggest that the zinc fingers are essential for normal MAP function in vivo, even though the in vitro enzyme assays indicate that they are not involved in catalysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Gen Genet 1995 Jan 20
PMID:Evidence that two zinc fingers in the methionine aminopeptidase from Saccharomyces cerevisiae are important for normal growth. 786 96

The conduction properties of inositol (1,4,5)-trisphosphate (InsP3)-gated calcium (Ca) channels (InsP3R) from canine cerebellum for divalent cations and the regulation of the channels by intraluminal Ca were studied using channels reconstituted into planar lipid bilayers. Analysis of single-channel recordings performed with different divalent cations present at 55 mM on the trans (intraluminal) side of the membrane revealed that the current amplitude at 0 mV and the single-channel slope conductance fell in the sequence: Ba (2.2 pA, 85 pS) > Sr (2.0 pA, 77 pS) > Ca (1.4 pA, 53 pS) > Mg (1.1 pA, 42 pS). The mean open time of the InsP3R recorded with Ca (2.9 ms) was significantly shorter than with other divalent cations (approximately 5.5 ms). The "anomalous mole fraction effect" was not observed in mixtures of divalent cations (Mg and Ba), suggesting that these channels are single-ion pores. Measurements of InsP3R activity at different intraluminal Ca levels demonstrated that Ca in the submillimolar range did not potentiate channel activity, and that very high levels of intraluminal Ca (> or = 10 mM) decreased channel open probability 5-10-fold. When InsP3R were measured with Ba as a current carrier in the presence of 110 mM cis potassium, a PBa/PK of 6.3 was estimated from the extrapolated value for the reversal potential. When the unitary current through the InsP3R at 0 mV was measured as a function of the permeant ion (Ba) concentration, the half-maximal current occurred at 10 mM trans Ba. The following conclusions are drawn from these data: (a) the conduction properties of InsP3R are similar to the properties of the ryanodine receptor, another intracellular Ca channel, and differ dramatically from the properties of voltage-gated Ca channels of the plasma membrane. (b) The estimated size of the Ca current through the InsP3R under physiological conditions is 0.5 pA, approximately four times less than the Ca current through the ryanodine receptor. (c) The potentiation of InsP3R by intraluminal Ca in the submillimolar range remains controversial. (d) A quantitative model that explains the inhibitory effects of high trans Ca on InsP3R activity was developed and the kinetic parameters of InsP3R gating were determined.
J Gen Physiol 1994 Nov
PMID:Inositol (1,4,5)-trisphosphate (InsP3)-gated Ca channels from cerebellum: conduction properties for divalent cations and regulation by intraluminal calcium. 787 25

1. Despite considerable progress, cancer continues to remain the number one health threat to human beings. Currently, the targeted antineoplastic therapy is based on an understanding of the molecular mechanisms that govern the normal proliferation and functioning of the cellular elements. Furthermore, the gene-directed therapies and antibody-based approaches are also based on modulating specific signalling processes influencing growth factors and oncogenes that alter cellular proliferation. 2. The intracellular level of metallothionein, a low molecular weight metal binding protein consisting of 25-30% cysteine, containing no aromatic amino acids or disulfide bonds and binding between 5 and 7 g atoms of group II B heavy metals per mole protein, may play an important role in regulating cellular responsiveness to DNA interactive antineoplastic agents. For example, cells with acquired resistance to cisplatin or chlorambucil overexpress metallothionein, which tends to bind these alkylating agents to a higher extent than the non-resistant cells. Since humans synthesize several isoforms of metallothionein. It is not certain which isoforms are increased in cells with acquired resistance to anti-cancer drugs. In addition to sequestering electrophilic anti-cancer drugs, metallothionein, by regulating the activities of zinc-requiring metalloenzymes or scavenging radical species, may alter the therapeutic efficacy of antineoplastic agents.
Gen Pharmacol 1994 Nov
PMID:Metallothionein in carcinogenesis and cancer chemotherapy. 789 39

Calcitriol [1,25(OH)2D3] actions on intestinal calcium transport involve genomic and nongenomic pathways. Whether nongenomic 1,25(OH)2D3-mediated actions are employed was investigated using isolated intestinal epithelial cells of naturally vitamin D-deficient underground-dwelling damara mole-rats (Cryptomys damarensis). 1,25(OH)2D3-mediated nongenomic pathways of intestinal calcium uptake, measured by opening of 1,25(OH)2D3-activated voltage-sensitive Ca2+ channels (VSCC), did not occur. Rapid (1 min) 45Ca2+ transmembrane influx in intestinal cells was not significantly increased by the addition of 1,25(OH)2D3 (at concentrations from 10(-12) to 10(-6) nM), when compared to opening of VSCC in the presence of a depolarizing (elevated K+) buffer. Furthermore, even after 30 min calcium uptake was not significantly enhanced by the hormone. These findings support earlier reports that duodenal calcium absorption is independent of vitamin D and is a highly adaptive feature of a subterranean existence.
Gen Comp Endocrinol 1994 Jul
PMID:Absence of calcitriol-mediated nongenomic actions in isolated intestinal cells of the damara mole-rat (Cryptomys damarensis). 792 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>