Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 molecular nature of formaldehyde (HCHO)-induced mutations was studied in both human lymphoblasts and E. coli. Thirty HPRT- human lymphoblast colonies induced by eight repetitive 150 microM HCHO treatments were characterized by Southern blot analysis. Fourteen of these mutants (47%) had visible deletions of some or all of the X-linked HPRT bands, indicating that HCHO can induce large losses of DNA in human lymphoblasts. In E. coli, DNA alterations induced by HCHO were characterized with use of the xanthine guanine phosphoribosyl transferase (gpt) gene as the genetic target. Exposure of E. coli to 4 mM HCHO for 1 hr induced large insertions (41%), large deletions (18%), and point mutations (41%). Dideoxy DNA sequencing revealed that most of the point mutations were transversions at GC base pairs. In contrast, exposure of E. coli to 40 mM HCHO for 1 hr produced 92% point mutations, 62% of which were transitions at a single AT base pair in the gene. Therefore, HCHO is capable of producing different genetic alterations in E. coli at different concentrations, suggesting fundamental differences in the mutagenic mechanisms operating at the two concentrations used. Naked pSV2gpt plasmid DNA was exposed to 3.3 or 10 mM HCHO and transformed into E. coli. Most of the resulting mutations were frameshifts, again suggesting a different mutagenic mechanism.
Environ Mol Mutagen 1988
PMID:Molecular analysis of formaldehyde-induced mutations in human lymphoblasts and E. coli. 290 Jul 62

Treatment of rats with the cytochrome P-450 suicide substrate, 3,5-diethoxycarbonyl-2,6-dimethyl-4-ethyl-1,4-dihydropyridine (DDEP), produced a 95% inhibition of the in vivo demethylation of either aminopyrine or morphine within 2 hr. One-carbon metabolism of formaldehyde or formate to carbon dioxide was not altered. DDEP also produced a time-dependent decrease in total hepatic microsomal cytochrome P-450 but had no effect on either NADPH-cytochrome c reductase or p-nitrophenol glucuronyl-transferase activities up to 24 hr after administration. A rapid decrease in rat liver microsomal aniline hydroxylation and ethoxyresorufin deethylation was observed in vitro following DDEP administration. Although in vitro testosterone metabolism to 16 alpha-, 16 beta-, and 2 alpha-hydroxy metabolites was depressed profoundly by DDEP in microsomes from untreated and 3-methylcholanthrene-treated animals, 7 alpha-hydroxylation of testosterone was much less affected. Immunochemical quantification of various microsomal cytochrome P-450 protein moieties showed that cytochromes P-450 beta NF-B, P-450UT-A, P-450PCN-E, and P-450PB-C were decreased in hepatic microsomes from DDEP-treated rats. However, the protein moiety of cytochrome P-450UT-H was not diminished and the immunoreactive protein for cytochromes P-450UT-F, P-450PB-B, and P-450ISF-G was only slightly decreased. These results show that DDEP treatment leads to marked decreases in holoprotein and apoproteins of many but not all hepatic microsomal cytochrome P-450 isozymes.
Mol Pharmacol 1986 Jan
PMID:Effect of the suicide substrate 3,5-diethoxycarbonyl-2,6-dimethyl-4-ethyl-1,4-dihydropyridine on the metabolism of xenobiotics and on cytochrome P-450 apoproteins. 308 Jun 74

The common approach is developed for isolation of mutants deficient in key enzymes of ribulose monophosphate pathway for formaldehyde oxidation and assimilation by obligate methylotrophic bacteria. The approach is based on total isolation of temperature sensitive mutants and their biochemical characterization. A number of ts- mutants of obligate methylotroph M. flagellatum KT is isolated following nitrosoguanidine induced mutagenesis. The modified screening method was developed and used for identification of mutants deficient in the key enzymes of ribulose monophosphate pathway. The mutant deficient in glucose-6-phosphate dehydrogenase (zwf) was identified. The NAD-dependent activity of glucose-6-phosphate dehydrogenase was not measurable under nonpermissive temperature while the level of NADP-dependent activity was only four-fold less comparing with wild type strain. It was concluded that growth limitation of zwf mutant of M. flagellatum KT (designated T623) at 42 degrees C results from the absence of NAD-dependent activity of glucose-6-phosphate dehydrogenase.
Mol Gen Mikrobiol Virusol 1987 Jul
PMID:[Temperature-sensitive mutant of the obligate methylotroph Methylobacillus flagellatum KT deficient in glucose-6-phosphate dehydrogenase]. 311 3

The activities of the key enzymes of ribulose monophosphate cycle for formaldehyde oxidation and assimilation were tested in crude extracts from temperature sensitive mutants of obligatemethylotroph M. flagellatum KT. Two mutants deficient in phosphoglucoisomerase activity were identified during this screening. Phosphoglucoisomerase of T525 pgi-1 mutant was active both at permissive (30 degrees C) and nonpermissive (42 degrees C) temperatures. Complete inactivation of the enzyme at 42 degrees C occurred in 2 h in vitro, while in vivo incubation at nonpermissive temperature for more than 10 h was required for the enzyme inactivation. Phosphoglucoisomerase activity of T566 pgi-2 was 5-fold lower as compared with the one from the parent strain incubated at 30 degrees C. The enzyme was inactivated in 2 min. in crude extract at nonpermissive temperature.
Mol Gen Mikrobiol Virusol 1987 Aug
PMID:[Characteristics of Methylobacillus flagellatum KT mutants, deficient for phosphoglucoisomerase, an enzyme of the ribulose monophosphate cycle of obligate methylotrophic bacteria]. 311 97

The hyperresistance to 4-nitroquinoline-N-oxide (4-NQO) and formaldehyde (FA) of yeast strains transformed with the multi-copy plasmids pAR172 and pAR184, respectively, is due to the two genes, SNQ and SFA, which are present on these plasmids. Restriction analysis revealed the maximal size of SFA as 2.7 kb and of SNQ as 2.2 kb, including transcription control elements. The presence of the smallest 2.7 kb subclone carrying SFA increased hyperresistance to formaldehyde fivefold over that of the original pAR184 isolate. No such increase in hyperresistance to 4-NQO was seen with the smaller subclones of the pAR172 isolate. Disruption of the SFA gene led to a threefold increase in sensitivity to FA as compared with the wild type. Expression of gene SNQ introduced on a multi-copy vector into haploid yeast mutants rad2, rad3, and snm1 did not complement these mutations that block excision repair.
Mol Gen Genet 1988 Feb
PMID:Genetic characterization of hyperresistance to formaldehyde and 4-nitroquinoline-N-oxide in the yeast Saccharomyces cerevisiae. 312 60

In order to provide data for meaningful interpretation and quantitation of immunogold labeling on cryosections their morphology and permeability to protein A-gold were evaluated: We studied plastic sections of immunogold-labeled ultrathin and semithick cryosections cut perpendicular to the original cryosection plane. Various soluble and insoluble antigens in different specimens (hemoglobin and histone H5 in chicken erythrocytes, tubulin in Leishmania cells, and outer membrane protein OmpA in Escherichia coli) were fixed with glutaraldehyde-formaldehyde, formaldehyde, or periodate-lysine-paraformaldehyde and incubated with specific antibodies and protein A-gold of different sizes. The cryosection surface may be rough or smooth depending both on the sectioned material and on dehydration and drying artifacts or possibly on the cutting process itself. Well-preserved sections are capable of withstanding considerable deformation without showing clefts or cracks. If the sectioned specimen is sufficiently fixed, protein A-gold is not able to enter the IgG-labeled sections significantly but follows surface irregularities. However, gold particles can be detected within visibly damaged sections.
J Ultrastruct Mol Struct Res
PMID:Transverse sectioning of plastic-embedded immunolabeled cryosections: morphology and permeability to protein A-colloidal gold complexes. 333 Sep 84

A brominated poly[d(G-C)].poly[d(G-C)] which forms a stable Z-DNA helix under physiological salt conditions was prepared. The rabbits were immunized with the brominated polynucleotide complexed with methylated bovine serum albumin. Antisera that are highly specific to the Z-DNA were produced: there is practically no interaction between the antisera and the native or denaturated DNA and the B-form of poly[d(G-C)].poly[d(G-C)]. This makes possible their use as reagents for determining the presence of Z-DNA in biological systems. A sensitive enzyme-linked immunosorbent assay (ELISA) that permits detection of 5 ng/ml Z-DNA was developed. This method was used for studying the B-Z transition and for antigenic determinant characterization. It was established, that formaldehyde amino-derivatives interact with the antigenic determinant and prevent the immunochemical assay of Z-DNA. The H1 and H3 histones prevent and and spermine increases the interaction of Z-DNA with antibodies.
Mol Biol (Mosk)
PMID:[Enzyme immunologic method for the study of left-handed DNA]. 344 47

Multiple reactions are thought to be involved in transforming dialkynitrosamines to active carcinogens. The first proposed step is enzymatic alpha-hydroxylation by the active oxygen species of cytochrome P-450, followed by nonenzymatic N-dealkylation and formation of diazohydroxides (RNNOH). The latter transformation can reasonably occur by a two-step mechanism via tautomerization of a monoalkylnitrosamine intermediate or directly from the alpha-hydroxylated species in one step. Both of these pathways in the transformation of hydroxymethylnitrosamine to diazohydroxide and formaldehyde were examined by the semiempirical molecular orbital method MNDO (modified neglect of diatomic differential overlap) and the ab initio method using STO-3G and 3-21G basis sets. Complete geometry optimizations of all reactants, intermediates, transition states, and products were performed. MNDO was also used to compare the similar transformation of the dimethyl analog. Both methods show that in the gas phase a concerted pathway involving a six-membered ring transition-state pathway is kinetically favored over a two-step pathway involving N-demethylation followed by tautomerization via two four-membered ring transition states. This reaction appears to be a viable one to formation of an ultimate carcinogen by parent dialkylnitrosamines in the hydrophobic substrate binding site of cytochrome P-450.
Mol Toxicol
PMID:Nitrosamine carcinogen activation pathway determined by quantum chemical methods. 344 50

The lipid-soluble folate antagonist, 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidin e (piritrexim; BW301U), induced misincorporation of dUMP in human B (SB)- and T (MOLT-4)-lymphoblastoid cells, and in human promyelocytic leukemia cells (HL-60). Analysis by alkaline sucrose gradients and alkaline elution indicated that 3H-DNA that had been labeled for 15 min distributed into progressively smaller DNA fragment sizes in a drug concentration-dependent manner from 0 microM to 50 microM piritrexim. This phenomenon was observed regardless of the labeled nucleotide precursor employed for detection of newly synthesized DNA [( 3H]deoxyuridine, [3H]deoxyadenosine, or [3H]deoxycytidine). In contrast, formaldehyde denaturation and sedimentation of DNA in neutral denaturing sucrose gradients released only 3-4% of the newly synthesized DNA as 3S-6S fragments (80-200 nucleotides), whereas the remaining population of newly synthesized DNA pelleted to the bottom of the tube. Failure to detect DNA fragmentation under neutral conditions to the extent observed under alkaline conditions indicated the presence of apurinic and apyrimidinic sites in DNA--lesions which would be expected in DNA undergoing excision-repair of misincorporated dUMP. Cytotoxicity resulting from dUMP misincorporation was consistent with the enhanced toxicity of piritrexim which was observed when HL-60 cells or MOLT-4 cells were exposed concurrently to exogenous deoxyuridine. Deoxyuridine-enhanced toxicity was demonstrated to be concentration dependent for both cell lines when piritrexim concentrations were marginally toxic. The cytotoxic effect of dUMP misincorporation was further substantiated by the observation that MOLT-4 cells treated with 0.5 microM piritrexim alone eventually developed resistance to the drug, whereas treatment with both piritrexim and 10 microM deoxyuridine prevented the selection of piritrexim-resistant cells.
Mol Pharmacol 1986 Dec
PMID:Drug concentration-dependent DNA lesions are induced by the lipid-soluble antifolate, piritrexim (BW301U). 349 Dec 87


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