Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A human gene and cDNA coding for a breast-cancer-associated antigen (H23Ag) were isolated and characterized. The gene contains two exons and one intron. Part of the second exon is a tandem repeat array (TRA) consisting of multiple 60-bp G + C-rich units. We report here the characterization of unique sequences that are found in the H23Ag gene and cDNA, in addition to the 60-bp repeats. Analysis of the cDNA sequences revealed a putative ATG start codon preceded by two overlapping initiation consensus sequences (CCACC). The open reading frame determines an amino acid (aa) sequence consisting of three regions. The first region contains an initiating methionine and a highly hydrophobic putative signal peptide. This is followed by a variable number of highly conserved 20-aa repeat units (TRA). The last region, C-terminal to TRA, contains four potential N-linked glycosylation sites. The genomic nucleotide sequences demonstrate a putative promoter region that includes a 'TATA' box. A putative estrogen regulatory element is located 5' to the promoter region. The characterization of the gene and cDNA coding for the H23Ag presented here, may help to elucidate its possible function in human breast cancer.
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PMID:Isolation and characterization of an expressed hypervariable gene coding for a breast-cancer-associated antigen. 168 29

The effects of neonatal exposure to delta-9-tetrahydrocannabinol (THC) on the adult animal brain neurochemistry and pain perception were evaluated. Newborn rat pups were culled to a litter size of 8 (males and females) and treated either with THC (2 mg/kg) or oil (control) daily, during days 1-4 after birth. After weaning, the THC-treated males were housed 4 per cage. During the juvenile period (day 50), the THC-treated animals exhibited significantly lower baseline tail-flick values (a measure of pain perception) than the control. However, as adults, the THC-treated animals exhibited significantly higher sensitivity to pain following 5 mg/kg morphine challenge. Furthermore, the THC-treated animals had significantly elevated beta-endorphin and methionine-enkephalin levels in almost all the brain areas sampled for the study. In addition, the neonatally THC-treated rats exhibited significantly higher levels of substance P (SP) and significantly lower levels of gonadotropin releasing hormone (GnRH) in the anterior hypothalamus-preoptic area. The SP and GnRH levels did not differ among the THC-treated and control animals in the medial basal hypothalamus. The results of this study indicate that even a very low dose of THC administered during the neonatal period has a long-lasting effect on the brain neurochemistry. In particular, neonatal administration of THC appears to alter functioning of the endogenous opioid system.
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PMID:Effect of early exposure to delta-9-tetrahydrocannabinol on the levels of opioid peptides, gonadotropin-releasing hormone and substance P in the adult male rat brain. 170 Sep 26

The mechanisms that underlie synaptic plasticity have been largely inferred from electrophysiological studies performed at sites remote from synaptic terminals. Thus the mechanisms involved in plasticity at the secretory sites have remained ill-defined. We have now used somatic synapses of cultured Helisoma neurones to directly assess presynaptic ion conductances and study the secretory apparatus. At these synapses we determined the actions of a modulatory neuropeptide, Phe-Met-Arg-Phe-NH2 (FMRFa), on the release of the neurotransmitter acetylcholine (ACh). Using voltage- and calcium-clamp techniques, we have demonstrated that FMRFa causes a presynaptic inhibition of ACh release by (1) reducing the magnitude of the voltage-dependent calcium current, and (2) regulating the secretory apparatus. The photolabile calcium cage, nitr-5 (refs 3-8), was dialysed into the presynaptic cell. In response to ultraviolet light, calcium was released from nitr-5 and ACh secretion was stimulated. Under conditions of constant internal calcium, FMRFa reduced the rate of ACh release. Thus we conclude that FMRFa reduces the influx of calcium during the action potential and decreases the sensitivity of the secretory apparatus to elevated internal calcium, thereby contributing to a presynaptic inhibition of transmitter release.
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PMID:A neuromodulator of synaptic transmission acts on the secretory apparatus as well as on ion channels. 247 76

The molecular species that determine the unique structure and functions of the microtubules in the mitotic spindle are not known. We describe the results of two new approaches to the molecular structure of the spindle. Both approaches rely on detergent-extracted preparations of synchronized populations of cells metabolically labeled with 35S-methionine or 32P-phosphate. In these preparations, the original cellular microtubules are preserved. The microtubule components can be released from the detergent-extracted preparations by selective depolymerization with calcium ions. Alternatively, the microtubules can be stabilized by taxol, freed of chromatin by digestion with DNAase and freed of the surrounding cage of intermediate filaments by further extraction at low ionic strength. Gel electrophoresis of each of these preparations of mitotic microtubules demonstrates that they contain microtubule-associated proteins that we have previously shown to be present in interphase microtubules. They also contain a protein of 150,000 daltons, which is the first mitosis-specific microtubule-associated protein identified in mammalian cells.
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PMID:Proteins specifically associated with the microtubules of the mammalian mitotic spindle. 612 Jul 67

Phenylethanolamine N-methyltransferase (PNMT) is the enzyme that catalyzes the S-adenosyl-L-methionine-dependent methylation of (-)norepinephrine to (-)epinephrine in the adrenal medulla. Adrenal PNMT activity is markedly different in two highly inbred rat strains; enzyme activity in the F344 strain is more than fivefold greater than that in the Buf strain. Initial characterization of the enzyme in the two inbred strains reveals evidence for catalytic and structural differences, as reflected in dissimilar Km values for the cosubstrate (S-adenosyl-L-methionine) and prominent differences in thermal inactivation curves. To assess adrenal PNMT activity in an F344 X Buf pedigree, we employed a statistical procedure to test for one- and two-locus hypotheses in the presence of within-class correlations due to cage or litter effects. The PNMT data in the pedigree are best accounted for by segregation at a simple major locus superimposed upon a polygenic background; data obtained from the biochemical studies suggest that the major locus is a structural gene locus.
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PMID:Inheritance of adrenal phenylethanolamine N-methyltransferase activity in the rat. 614 73

Many different types of cancer cells have been shown to be methionine-dependent. These cells, unlike normal cells, grow poorly or not at all when methionine is replaced by its immediate precursor homocysteine in the growth medium (Met- Hcy+ medium). We have previously shown that apparently normal total amounts of methionine are synthesized by methionine-dependent SV40-transformed human fibroblasts. However, methionine-dependent cells in Met- Hcy+ medium accumulate reduced amounts of S-adenosylmethionine (AdoMet) and elevated amounts of S-adenosylhomocysteine (AdoHcy) that together probably limit growth. In this report, we demonstrate that the amount of free methionine is low in methionine-dependent SV40-transformed human fibroblasts in Met- Hcy+ medium compared to normal human diploid fibroblasts. In contrast, in Met+ Hcy- medium, the amount of free methionine is comparable in both cell types. The deficient pool of free methionine in methionine-dependent cells in Met- Hcy+ medium allows only low amounts of AdoMet to be formed. However, large amounts of the biosynthesized methionine are channeled into protein synthesis. Possible mechanisms are discussed to explain this cancer-associated metabolic defect.
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PMID:Reduced free-methionine in methionine-dependent SV40-transformed human fibroblasts synthesizing apparently normal amounts of methionine. 631 51

The performance of dwarf and normal White Leghorn laying hens with similar genotypes other than for the dwarf gene (dw) was observed over thirteen 28-day periods in a factorial arrangement involving four protein levels (20.0, 18.1, 16.4 or 14.3% protein plus supplemental methionine) and two densities (two or three birds per standard 10 X 16 in cage). The normal birds had significantly higher overall hen-day egg production, egg weight, and body weight, but the dwarf birds excelled for feed efficiency and adult viability. Significant genotype X ration interactions were observed for egg lay, egg weight, body weight, and feed efficiency, primarily due to the relatively poor performance of the dwarf birds on the 14% protein. A significant genotype X density interaction resulted for feed efficiency, due to a higher efficiency in 3-bird than in 2-bird cages for dwarf birds, while the reverse was true for normal birds. These results suggest that the potential of the dwarf gene for increasing the efficiency of commercial egg layers can be enhanced by further study as to optimal nutrition and management regimens.
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PMID:Performance of dwarf and normal laying hens as influenced by protein level and cage density. 665 57

Feather loss was scored on the neck and crop area of 402 individually-caged hens, 61 weeks old and receiving either methionine-deficient or adequate diets. Both feather loss and egg production were greater for the hens receiving adequate diets. Within treatments there was a close relationship between egg output and feather loss. The findings are consistent with feather loss being caused by abrasion against the cage floor or walls during pre-laying behaviour.
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PMID:The effects of methionine deficiency and egg production on feather loss in caged layers. 666 92

In a first trial, 21 five-week old rabbits housed in individual cages were divided into 3 experimental lots. All of them received the same lysine-deficient pelleted diet but lot 1 drank pure water only, lot 2 had a free choice between a solution of l-lysine (1.6 g/l) or pure water, and lot 3 drank l-lysine only. The trial lasted 24 days. The growth of lot 1 rabbits was significantly lower than that of lot 3 rabbits. The performance of lot 2 animals was intermediate but quite similar to that of lot 3. The lot 2 animals drank significantly more of the lysine solution than pure water (56 vs 44 p. 100). In a second trial, 60 five-week old rabbits housed 5 to a cage were divided into 4 lots. Lot 1 received a sulphur amino acid (AAS)-deficient diet + pure water, lot 2 a balanced diet + pure water, lot 3 the deficient diet + pure water and a solution of dl-methionine (1 g/l), and lot 4 the deficient diet + pure water + another dl-methionine solution (3 g/l). The trial lasted 19 days. Lot 2 showed improved growth due to the intake of the better AAS balanced diet. Lot 3 and 4 rabbits had intermediate growth which approached that of lot 2 animals as the methionine concentration in the solution increased. In both cases, the rabbits preferred the methionine solution to the pure water: 77 p. 100 in lot 3 (1 g/l) and 60 p. 100 in lot 4 (3 g/l). In conclusion, when the diet was deficient in AAS or in lysine and there was a free choice between either pure water or a solution of the deficient amino acid, the rabbits preferred the solution.
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PMID:[Water and food ingestion in the young rabbit given food deficient in methionine or lysine and drinking by free choice a solution of that amino acid or pure water]. 681 36

Nitric oxide and superoxide, which are produced by several cell types, rapidly combine to form peroxynitrite. This reaction can result in nitric oxide scavenging, and thus mitigation of the biological effects of superoxide. Also, superoxide can trap and hence modulate the effects of nitric oxide; superoxide dismutase, by controlling superoxide levels, therefore can influence the reaction pathways open to nitric oxide. The production of peroxynitrite, however, causes its own sequelae of events: Although neither .NO nor superoxide is a strong oxidant, peroxynitrite is a potent and versatile oxidant that can attack a wide range of biological targets. The peroxynitrite anion is relatively stable, but its acid, peroxynitrous acid (HOONO), rearranges to form nitrate with a half-life of approximately 1 s at pH 7, 37 degrees C. HOONO exists as a Boltzmann distribution of rotamers; at 5-37 degrees C HOONO has an apparent acidity constant, pKa,app, of 6.8. Oxidation reactions of HOONO can involve two-electron processes (such as an SN2 displacement) or a one-electron transfer (ET) reaction in which the substrate is oxidized by one electron and peroxynitrite is reduced. These oxidation reactions could involve one of two mechanisms. The first mechanism is homolysis of HOONO to give HO. and .NO2, which initially are held together in a solvent cage. This caged pair of radicals (the "geminate" pair) can either diffuse apart, giving free radicals that can perform oxidations, or react together either to form nitrate or to reform HOONO (a process called cage return). A large amount of cage return can explain the small entropy of activation (Arrhenius A-factor) observed for the decomposition of HOONO. A cage mechanism also can explain the residual yield of nitrate that appears to be formed even in the presence of high concentrations of all of the scavengers studied to date, since scavengers capture only free HO. and .NO2 and not caged radicals. If the cage mechanism is correct, the rate of disappearance of peroxynitrite be slower in solvents of higher viscosity, and we do not find this to be the case. The second mechanism is that an activated isomer of peroxynitrous acid, HOONO*, can be formed in a steady state. The HOONO* mechanism can explain the inability of hydroxyl radical scavengers to completely block either nitrate formation or the oxidation of substrates such as methionine, since HOONO* would be less reactive, and therefore more selective, than the hydroxyl radical itself.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. 776 72


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