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Query: UNIPROT:P06889 (Mol)
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1H-NMR spectroscopy was used to monitor the major metabolic end products released by Giardia lamblia when maintained anaerobically in culture in Diamond's TYI-S-33 medium. Spectra were acquired for the cell-free medium and the resonances of metabolites utilised and produced during cell growth identified by the addition of pure compounds and by difference spectroscopy. The major metabolites produced by the parasite were alanine, ethanol and acetate, with increases in concentrations in the media after 4 days' growth (end of log phase) of 18, 15 and 4 mM, respectively. The production of both alanine and ethanol approximated to cell growth, with ethanol formation lagging behind alanine during log growth but predominating after the parasites entered stationary phase. Acetate was formed at a more constant rate during growth. Glucose utilisation was sufficient to account for only 50% of the total carbon appearing in alanine, ethanol and acetate. The aminotransferase inhibitors L-cycloserine and carboxymethoxylamine inhibited growth and selectively inhibited the production of alanine. Analysis of the amino acid composition of the medium by HPLC showed that the only amino acid produced, apart from alanine, was proline, which increased in concentration in the medium by 4 mM after 4 days. There was also a 7 mM increase in ammonia over the same period. The only amino acids that were utilised were arginine and the components of an unresolved peak comprising serine, asparagine and glutamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Biochem Parasitol 1989 Nov
PMID:Alanine is a major end product of metabolism by Giardia lamblia: a proton nuclear magnetic resonance study. 261 87

We have identified useful target sites for the diagnosis of malaria infections by oligonucleotide hybridization on the small subunit RNA of Plasmodium falciparum. Acetic acid works as effectively as formaldehyde or methyl mercuric hydroxide in procedures designed to apply RNA to filters. We have confirmed the findings of others that the stability of ribosomal RNA suffices for its use as a target for diagnosis. We have achieved a detection level of at least 0.00046% parasitemia and suggest that detection of a single parasite is well within reach of this technology.
Mol Biochem Parasitol 1989 Aug
PMID:Ribosomal RNA-based diagnosis of Plasmodium falciparum malaria. 268 39

The 4-(m-OH-phenyl)piperidines are a flexible fragment of the morphine/benzomorphan fused-ring opioids. Analogs in this family were synthesized with varying 4-alkyl substituents increasing in bulk from H through methyl, n-propyl, to t-butyl, each with the three N-substituents methyl, allyl, and phenethyl. These twelve compounds were evaluated for analgetic agonism in mice using two different models for antinociceptive activity, acetic acid writhing and tail-flick, the latter by both subcutaneous and intracerebroventricular routes of administration. Antagonism to morphine analgesia was also measured by the mouse tail-flick procedure. Binding affinities of these new analogs to different opioid receptor subtypes were determined. Energy conformational calculations on these compounds were also carried out using the empirical energy program called MOLMEC, in order to better understand how the 4-R substituents modulate receptor binding affinities and efficacies. The results obtained show that, in general, the compounds studied are mu-selective and vary in agonist potency from weak to morphine-like. Significant differences in rank order of analgetic potencies and their relationship to receptor affinities were obtained from the results of subcutaneous and intracerebroventricular administration. Results of energy-conformational calculations for twelve N-methyl compounds indicate that those with 4-alkyl substituents favor a common, non-morphine-like phenyl axial conformation. The 4-t-butyl compounds are, in fact, the first simple mono-alkyl-substituted 4-phenyl-piperidines predicted to definitely exist in a phenyl axial conformation, as confirmed by X-ray analysis. On the basis of this common phenyl axial conformation, the observed variation in mu receptor affinities and efficacies of the 4-methyl, 4-n-propyl, and 4-t-butyl compounds could be understood and the behavior of 4-ethyl and 4-isopropyl analogs predicted. Two equatorial conformers (rotamers) were found to be the preferred forms of the analogs with 4-R being H or an ester group, or with a 3-methyl group added trans (beta) to the 4-R group. Taking into account the rotational flexibility of these analogs, these two conformers could be used to understand differences in high and low efficacy compounds observed among analogs with preferred phenyl equatorial conformations. None of the analogs exhibit a fused-ring-like N-substituent modulation of efficacy. This result can, perhaps, be understood by their inability in any proposed conformer to totally mimic key receptor interactions of both the phenol-OH and N-substituent portions of the fused compounds.
Mol Pharmacol 1988 Sep
PMID:Structure-activity studies of morphine fragments. I. 4-alkyl-4-(m-hydroxy-phenyl)-piperidines. 284 51

A new method is described for flow cytometric cell cycle analysis of normal and psoriatic human epidermis, based on non-enzymatic tissue disaggregation. The epidermis was isolated by treatment with acetic acid and stored by freezing. After thawing, the epidermis was disintegrated into a nuclear suspension by 3 steps: incubation with dithiotreitol, whirling in a buffer (pH 7.4) with the non-ionic detergent Nonidet P40, EGTA, RNase and spermine, and whirling after addition of citric acid to a final concentration of 1% (pH 2.4). The suspension was stained with propidium iodide and filtered before flow cytometry. The yield of suspended nuclei was approximately 70% of the original number of cells in the tissue. The detergent/citric acid method was found to be preferable to an ultrasonication method previously used on human epidermis. All cell cycle and cell maturation stages were represented in the detergent/citric acid suspension, in contrast to the selection of immature G1, S and G2 stages with enzymatic methods. In the analysis of psoriatic epidermis inadequately matured (parakeratotic) cells were present in the suspension and had to be discriminated by gating on light scattering intensity, as they were not susceptible to lysis and did not stain properly. The fraction of S phase nuclei was on average 1.9% in normal and 7.7% in psoriatic epidermis, thus confirming the results of other investigators using enzymes. The presence of mitotic figures in the suspension was demonstrated by flow sorting. In this way the mitotic fraction was estimated to 0.06% in normal and 0.22% in psoriatic epidermis, confirming histological data of other investigators.
Virchows Arch B Cell Pathol Incl Mol Pathol 1985
PMID:A method for flow cytometric cell cycle analysis of normal and psoriatic human epidermis based on a detergent/citric acid technique for suspension of nuclei. 285 98

The distribution of proteins of mosquito midgut forms of Plasmodium gallinaceum in the detergent-free (aqueous) and detergent-enriched phases was studied using a phase separation technique in Triton X-114. Of the three surface proteins on gametes and newly fertilized zygotes (240, 56, and 54 kDa) immunoprecipitated by transmission blocking monoclonal antibodies, 240 kDa protein was recovered in the aqueous phase, whereas 56 and 54 kDa proteins were found preferentially in the detergent phase. The hydrophobic properties of the 56 and 54 kDa proteins were also shown by their strong tendency to interact with the lipid bilayers and a hydrophobic matrix phenyl-Sepharose. Monoclonal antibody IID3B3 immunoprecipitated all the three proteins from the whole Triton extract but in the phase-separated extracts reacted only with the 240 kDa protein in the aqueous phase and not with the 56 and 54 kDa doublet in the detergent phase. In Western blot analysis also monoclonal antibody IID3B3 reacted only with the 240 kDa protein. The 240 kDa protein in the aqueous phase was retained by monoclonal antibody IID3B3 linked to Sepharose 4B beads and could be eluted either with 0.1 M acetic acid or 50 mM diethylamine. The 56 and 54 kDa doublet in the detergent phase could be bound to and eluted from Sepharose 4B beads-linked monoclonal antibody IID4 or rabbit anti-male P. gallinaceum gamete serum. Two stage-specific glycoproteins of 26 and 28 kDa on the surface of ookinetes of P. gallinaceum were also separated in the detergent phase following Triton X-114 extraction. Phase separation in Triton X-114 offers a simple approach to the separation of a select group of proteins from the bulk of the cellular proteins.
Mol Biochem Parasitol 1985 Dec
PMID:Phase separation in Triton X-114 of antigens of transmission blocking immunity in Plasmodium gallinaceum. 286 67

Immunohistochemical techniques have been used to localize clotting factor XIII subunit A in human reactive lymphoid follicles. The follicular dendritic reticulum cells (DRCs) were identified by the monoclonal antibodies R4/23 and OKB-7 as well as by their 5'-nucleotidase positivity. Follicular histiocytic reticulum cells (HRCs) were demonstrated by their acid phosphatase and non-specific esterase reactions. Capillaries were selectively visualized by adenosine triphosphatase. The immunohistochemical demonstration of F-XIIIa was preferably carried out in combination with one or two of the above marker techniques, on the same cryostat section. The subunit A of factor XIII is present in follicular DRCs. Their selective immunohistochemical demonstration with antibody against F-XIIIa requires formaldehyde fixation of cryostat sections. Similar fixation, however, is inappropriate for the demonstration of F-XIIIa reactivity of DRCs in paraffin sections. For this purpose, acetic acid-formalin fixation is useful. Follicular HRCs are consistently negative for F-XIIIa, contrary to the F-XIIIa positivity of sinusoidal and interfollicular HRCs. Developmental and functional implications of F-XIIIa reactivity in DRCs and HRCs are suggested.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Selective visualization of human dendritic reticulum cells in reactive lymphoid follicles by the immunohistochemical demonstration of the subunit A of factor XIII (F-XIIIa). 288 67

The intracellular parasite, Plasmodium falciparum, was found to synthesize a peptide similar to mammalian somatostatin. High performance liquid chromatography of acetic acid extracts of Plasmodium-infected erythrocytes revealed a metabolically labeled peptide that co-eluted with rat somatostatin and that was reactive with antibody against rat somatostatin. Bioassay of partially purified Plasmodium peptide demonstrated somatostatin activity. Acetic acid extracts from non-synchronized infected cultures were shown by radioimmunoassay to contain the equivalent of 150 molecules of somatostatin per parasite. Somatostatin was not detectable in erythrocytes of non-infected cultures.
Mol Biochem Parasitol 1987 Aug
PMID:Synthesis of a somatostatin-like peptide by Plasmodium falciparum. 289 Jan 2

The in vitro secretion of immunoreactive somatomedin C/insulin-like growth factor I (IR Sm-C/IGF-I) by two human breast cancer cell lines, MCF-7 and EVSA-T has been studied. IR Sm-C/IGF-I concentration showed a linear increase in serum-free culture media over 72 h of incubation for both cell lines, and a close correlation with cell number (P less than 0.001). To characterize this immunoreactivity, a pool of conditioned media collected after 72 h of incubation was dialyzed overnight against 1 M acetic acid, lyophilized, and gel filtered on a Sephadex G-50 column. Fractions were determined for Sm-C/IGF-I content and for the presence of a specific carrier for Sm-C/IGF-I. Two peaks of Sm-C/IGF-I-like immunoreactivity were evidenced, the first in the high molecular weight region and the second corresponding to the molecular weight of the free peptide. The first peak evidenced also a specific binding ability for radioiodinated Sm-C/IGF-I, suggesting that the activity found in this region could be interpreted as interference of the specific free binding sites in the immunoassay. Analysis of this peak by polyacrylamide gel electrophoresis demonstrated the presence of a specific binding for Sm-C/IGF-I in a molecular weight range between 35,000 and 45,000 Da, which was not modified in reducing conditions. The binding activity was competitively inhibited by addition of cold Sm-C/IGF-I but not by insulin excess.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1987 Dec
PMID:Partial characterization of somatomedin C-like immunoreactivity secreted by breast cancer cells in vitro. 296 40

Kline et al. (1980) have reported that indole-3-acetic acid (IAA) and four other indole derivatives are able to substitute for cAMP in activating expression of the ara regulon of E. coli. We have examined this phenomenon in detail, utilizing fusions between the structural gene for beta-galactosidase and the promoters for the araBAD, araE, and araFG operons. We confirm that IAA potently stimulates transcription from the araBAD promoter. The effect is highly specific to araBAD, as IAA has no, or only slight, effects on the araE and araFG operons. However, contrary to the results of Kline et al., we find that the action of IAA does not require CAP. Thus, IAA fully stimulates the transcription of araBAD in a strain which bears a complete deletion of the crp gene.
Mol Gen Genet 1985
PMID:The catabolite gene activator protein (CAP) is not required for indole-3-acetic acid to activate transcription of the araBAD operon of Escherichia coli K-12. 299 82

The herbicide sulfometuron methyl inhibits acetolactate synthase II of Salmonella typhimurium, resulting in toxic accumulation of alpha-ketobutyrate. Four mutants, containing Tn10 insertions in the acetate kinase (ack) or phosphotransacetylase (pta) genes, were found among a collection of mutants hypersensitive to sulfometuron methyl. The genetic map location of these four Tn10 insertions at 46 min was identical to that of ack and pta point mutants. The insertion and point mutants shared the following phenotypes: resistance to fluoroacetate, sensitivity to alizarin yellow, inability to utilize inositol as a sole carbon source, and hypersensitivity to sulfometuron methyl. Three of the four Tn10 insertion mutants were deficient in phosphotransacetylase but not in acetate kinase activities, indicating insertion of Tn10 in the pta gene. The fourth mutant contained an insertion in the ack gene and was deficient in both acetate kinase and phosphotransacetylase activities. This polarity is consistent with cotranscription of ack and pta. All ack and pta mutants tested were defective in alpha-ketobutyrate turnover. Acetate kinase and phosphotransacetylase are proposed to be part of a pathway for alpha-ketobutyrate metabolism. Propionyl-CoA, an intermediate of that pathway, and propionate, the product of the pathway, accumulated upon inhibition of acetolactate synthase.
Mol Gen Genet 1987 May
PMID:Involvement of ack-pta operon products in alpha-ketobutyrate metabolism by Salmonella typhimurium. 303 1


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