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PubMed1997

DNA adduct formation in primary mouse embryo cells induced by 7H-dibenzo[c,g]carbazole and its organ-specific carcinogenic derivatives.

The nuclease P1 modification of the 32P-postlabeling technique was used to study the biological activity of 7H-dibenzo[c,g]carbazole (DBC) and some of its derivatives, including N-methyldibenzo[c,g]carbazole (N-MeDBC), 5,9-dimethyldibenzo[c,g]carbazole (5,9-diMeDBC), 5,9,N-trimethyldibenzo[c,g]carbazole (5,9,N-triMeDBC), 6-methoxydibenzo[c,g]carbazole (6-McODBC), N-acetyldibenzo[c,g]carbazole (N-AcDBC), N-hydroxymethyldibenzo[c,g]carbazole (N-HMeDBC) in primary mouse embryo cells. A very good correlation was found between carcinogenic specificity in vivo of these N-heterocyclic aromatic hydrocarbons and their DNA-adduction in vitro. Primary mouse embryo cells were able to metabolize and detect tissue-specific sarcomagens N-MeDBC and 6-MeODBC as well as derivatives with both sarcomagenic and hepatocarcinogenic activity, DBC, N-AcDBC, and N-HMeDBC. The strong specific hepatocarcinogen 5,9-diMeDBC in vivo, did not induce any DNA-adducts in the embryo cells, which suggests that the enzymatic composition of the target tissue probably is the determining factor in the organ specificity of this derivative. 5,9,N-triMeDBC, derivative without any carcinogenic activity in vivo, did not induce any DNA-adducts in primary mouse embryo cells. Pretreatment of cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) apparently stimulated DNA-adduct formation in the cells exposed to DBC, 6-MeODBC, and N-MeDBC. No or a very slight effect of TCDD on DNA-adduct formation was found in cells exposed to N-HMeDBC and N-AcDBC. Preliminary results have shown that TCDD slightly induced cytochrome P4501A1-linked ethoxyresorufin O-deethylase (EROD) activity in primary mouse embryo cells. These data suggest the role of cytochrome P4501A1 in the metabolism of DBC derivatives with sarcomagenic activity.

Animals↗
PubMed1995

5'-regulatory region of Agrobacterium tumefaciens T-DNA gene 6b directs organ-specific, wound-inducible and auxin-inducible expression in transgenic tobacco.

The regulatory activity of a 826 bp DNA fragment located upstream of the pTiBo542 TL-DNA gene 6b coding region was analyzed in transgenic tobacco, using beta-glucuronidase (gus) as a reporter gene. The region was shown to drive organ-specific, wound- and auxin-inducible expression of the reporter, the effect being dependent on the type and concentration of auxin.

Agrobacterium tumefaciens↗
PubMed1987

Organ-specific and dosage-dependent expression of a leaf/stem specific gene from potato after tagging and transfer into potato and tobacco plants.

ST-LS1, a single copy gene from potato displaying a leaf/stem specific gene expression, was tagged by an exon modification and introduced into both potato and tobacco cells using Agrobacterium vectors. After regeneration of whole plants, the expression of the tagged gene was analyzed with respect to its organ specificity and compared to the expression of the corresponding resident gene. The expression of the transferred gene in transgenic plants closely followed the expression of the resident gene. No marked influence of the plant species serving as host was observed. The level of expression of the introduced gene varied by a factor of at least 100 in independent transformants when normalized to the expression of the resident gene. Southern analysis performed on the transformed plants indicated a correlation between copy number of the introduced gene and its expression level. The activity of the tagged gene as well as of the resident gene was significantly inhibited by treatment of the transgenic plants with the herbicide norfluorazon, indicating that this gene activity is dependent on the presence of functional chloroplasts in the leaves.

DNA, Recombinant↗
PubMed2001

Panax ginseng--a non-organ-specific cancer preventive?

For the past 50 years, the main weapons in the war against cancer have been early detection and surgical removal, radiotherapy, chemotherapy, and attempts to develop gene therapy. However, the results so far are less than ideal. One strategy now is to switch from therapeutic approaches to prevention of cancer by improving lifestyle and by identifying effective natural products as chemopreventive agents. One promising candidate with cancer-preventive effects that are not specific to any organ is Panax ginseng C A Meyer, a herb with a long medicinal history. Its protective influence against cancer has been shown by extensive preclinical and epidemiological studies, but these effects need to be carefully investigated by scientific clinical trials focusing on the major cancer killers stomach, lung, liver, and colorectal cancer.

Case-Control Studies↗
PubMed2006

Phosphorus and aluminum interactions in soybean in relation to aluminum tolerance. Exudation of specific organic acids from different regions of the intact root system.

Aluminum (Al) toxicity and phosphorus (P) deficiency often coexist in acid soils that severely limit crop growth and production, including soybean (Glycine max). Understanding the physiological mechanisms relating to plant Al and P interactions should help facilitate the development of more Al-tolerant and/or P-efficient crops. In this study, both homogeneous and heterogeneous nutrient solution experiments were conducted to study the effects of Al and P interactions on soybean root growth and root organic acid exudation. In the homogenous solution experiments with a uniform Al and P distribution in the bulk solution, P addition significantly increased Al tolerance in four soybean genotypes differing in P efficiency. The two P-efficient genotypes appeared to be more Al tolerant than the two P-inefficient genotypes under these high-P conditions. Analysis of root exudates indicated Al toxicity induced citrate exudation, P deficiency triggered oxalate exudation, and malate release was induced by both treatments. To more closely mimic low-P acid soils where P deficiency and Al toxicity are often much greater in the lower soil horizons, a divided root chamber/nutrient solution approach was employed to impose elevated P conditions in the simulated upper soil horizon, and Al toxicity/P deficiency in the lower horizon. Under these conditions, we found that the two P-efficient genotypes were more Al tolerant during the early stages of the experiment than the P-inefficient lines. Although the same three organic acids were exuded by roots in the divided chamber experiments, their exudation patterns were different from those in the homogeneous solution system. The two P-efficient genotypes secreted more malate from the taproot tip, suggesting that improved P nutrition may enhance exudation of organic acids in the root regions dealing with the greatest Al toxicity, thus enhancing Al tolerance. These findings demonstrate that P efficiency may play a role in Al tolerance in soybean. Phosphorus-efficient genotypes may be able to enhance Al tolerance not only through direct Al-P interactions but also through indirect interactions associated with stimulated exudation of different Al-chelating organic acids in specific roots and root regions.

Adaptation, Physiological↗
PubMed2003

Organ-specific changes in high-energy phosphates after hemorrhagic shock and resuscitation in the rat.

BACKGROUND: Adenosine nucleotides provide energy for many essential cellular functions. Liver and intestinal ATP and energy charge are known to decrease during hemorrhagic shock, and the ability to regenerate high-energy phosphates may have important implications for recovery. We measured organ-specific changes in energy charge after hemorrhagic shock and after shock followed by resuscitation. STUDY DESIGN: Anesthetized Sprague-Dawley rats were bled and maintained at a mean arterial pressure (MAP) of 40 mmHg for 1, 2, 3, or 4 hours. Some animals were resuscitated with normal saline and shed blood (1:1) to a mean arterial pressure of 80 to 90 mmHg for 1 hour. Control animals were anesthetized, but not hemorrhaged. At the conclusion, blood gases and adenine nucleotides were measured. RESULTS: Arterial pO2 and pCO2 were normal in all groups. Unresuscitated hemorrhage caused metabolic acidosis, but bicarbonate was normal in controls and after hemorrhage followed by resuscitation. Energy charge (EC) in the gastrocnemius was unaffected by hemorrhage or resuscitation. Liver EC decreased after hemorrhage (p = 0.0001), but recovered partially after resuscitation. Kidney EC was decreased after only 3 hours of hemorrhage and 1 hour of resuscitation (p = 0.005), but not with shorter periods of hemorrhage. Lung EC decreased with shock, but was substantially worse after resuscitation (p < 0.05). CONCLUSIONS: After hemorrhage and resuscitation, EC decreased in lung, liver, kidney, and intestine, but the time course, extent of decline, and ability to recover after resuscitation varied from organ to organ. Inability to regenerate high-energy phosphates after hemorrhagic shock may be a marker for more severe cellular damage.

Adenosine Diphosphate↗
PubMed2002

Organ-specific cell division abnormalities caused by mutation in a general cell cycle regulator in C. elegans.

The precise control of cell division during development is pivotal for morphogenesis and the correct formation of tissues and organs. One important gene family involved in such control is the p21/p27/p57 class of negative cell cycle regulators. Loss of function of the C. elegans p27 homolog, cki-1, causes extra cell divisions in numerous tissues including the hypodermis, the vulva, and the intestine. We have sought to better understand how cell divisions are controlled upstream or in parallel to cki-1 in specific organs during C. elegans development. By taking advantage of the invariant cell lineage of C. elegans, we used an intestinal-specific GFP reporter in a screen to identify mutants that undergo cell division abnormalities in the intestinal lineage. We have isolated a mutant with twice the wild-type complement of intestinal cells, all of which arise during mid-embryogenesis. This mutant, called rr31, is a fully dominant, maternal-effect, gain-of-function mutation in the cdc-25.1 cell cycle phosphatase that sensitizes the intestinal lineage to an extra cell division. We showed that cdc-25.1 acts at the G1/S transition, as ectopic expression of CDC-25.1 caused entry into S phase in intestinal cells. In addition, we showed that the cdc-25.1(gf) requires cyclin E. The extra cell division defect was shown to be restricted to the E lineage and the E fate is necessary and sufficient to sensitize cells to this mutation.

Amino Acid Sequence↗
PubMed1990

Lymphocyte adhesion to cultured Peyer's patch high endothelial venule cells is mediated by organ-specific homing receptors and can be regulated by cytokines.

Adhesion of lymphocytes to high endothelial venule (HEV) cells is the first step in the migration of these cells from blood into lymph nodes and Peyer's patches (PP). In the present study, we isolated and cultured HEV cells from PP of the rat and assessed their capacity to interact with lymphocytes. Flow cytometric analysis with a rat HEV-specific mAb KJ-4 revealed that greater than 90% of the cultured cells were stained by the antibody. Furthermore, confluent monolayers of PP HEV cells retained the capacity to support the adhesion of lymphocytes from spleen, thoracic duct, and lymph nodes but not binding of immature cells from thymus and bone marrow, which are deficient in cells capable of binding to HEV in vivo. In addition, intraepithelial lymphocytes that preferentially migrated into mucosal lymphoid tissues were also enriched in cells that adhered to the endothelial monolayers. The binding process required energy, was calcium-dependent, and could be inhibited by cytochalasin D, trypsin, and mixed glycosidase. Interestingly, pretreatment of PP HEV cells with rTNF, IFN-gamma, or granulocyte-macrophage CSF significantly increased the endothelial adhesiveness for thoracic duct lymphocytes in a time- and dose-dependent manner. In contrast, stimulation of lymphocytes with phorbol ester or TNF resulted in the rapid modulation of the surface expression of the PP homing receptor and decrease in lymphocyte binding to normal or TNF-stimulated HEV cells. The adhesion of lymphocytes to normal or cytokine-stimulated HEV cells can be blocked by pretreatment of lymphocytes, but not HEV cells, with the PP homing receptor-specific 1B.2.6 antibody. Taken together, these experiments provide strong evidence that the interaction between lymphocytes and cultured HEV cells are mediated by adhesive mechanisms that regulate lymphocyte entry into PP in vivo and that cytokines can promote HEV adhesiveness for lymphocytes through increased expression of organ-specific ligands on HEV cells.

Animals↗
PubMed1975

The effect of species and organ-specific features of tissue systems on the reactogenic and immunogenic properties of influenza virus.

The dynamics of changes in the reactogenic and immunogenic properties of influenza A/Hong Kong/1/68 (H3N2) virus in the course of serial passages in white mice, chick embryos, chick, cow and pig embryo kidney tissue cultures and in rat, guinea pig, chick embryo, cow embryo and pig embryo trachea organ cultures was studied. The rate of virus attenuation was found to depend not only on the species origin of tissue systems but also on their organ specificity. In rapid, 24-hour passages in chick embryos attenuation of the virus developed more rapidly and its immunogenic potency was retained better than in 48-hour passages or cultivation in another tissue system.

Administration, Intranasal↗
PubMed1978

[Organ specificity and cytotoxic properties af autoantibodies in brucellosis].

The presence of freely circulating autoantibodies was studied in patients with various clinical forms of brucellosis. Autoantibodies to the tissues of the liver, lymph nodes, spleen and the heart were revealed in the patients with acute, subacute, and chronic brucellosis. Investigations directed to ascertain the biological role of autoantibodies in brucellosis pointed to the organ specificity. Results of determination of the influence of the circulating antibodies on the intensity of tissue respiration and the processes of dehydration in the hepatic tissue showed antihepatic autoantibodies to produce a cytotoxic (aggressive) action. This confirmed a definite significance of autoimmune processes in the pathogenesis of brucellosis.

Autoantibodies↗
PubMed1997

Two growth-related organ-specific cDNAs from Cicer arietinum epicotyls.

Two cDNAs, CanST-1 and CanST-2, encoding two different growth-related organ-specific sequences have been isolated from a cDNA library from growing epicotyls of Cicer arietinum. An intriguing property of these two clones is the presence in their coding region of a repeated sequence which is highly conserved except for the number of repeats. The corresponding genes of CanST-1 and CanST-2 encode for proteins related to elongation processes. CanST-1 and CanST-2 are up-regulated during epicotyl growth, the transcript levels of both clones decrease when the growth of epicotyls is inhibited by several treatments and their expression increases when epicotyls resume growth. Furthermore, clones CanST-1 and CanST-2 are tissue-specific and are only expressed in epicotyls, mesocotyls, roots and stem tissues whose cells undergo elongation processes. Neither clone was found to be expressed in other organs such as cotyledons, leaves, flowers, pods and immature seeds. The results of auxin (IAA) and brassinolides (BR) treatments suggest that the processes in which the proteins encoded by CanST-1 and CanST-2 are involved are not mediated by these hormones.

Amino Acid Sequence↗
PubMed1997

[Organ specificity in the development of the epithelial lining of the oral cavity and esophagus].

Epithelial lining of upper portion of alimentary tract differs sharply from other digestive system portions. This is associated primarily with the peculiarities of local processes of morphogenesis. Intertissular interactions, as well as changes in architectonics and differentiation of the structures, surrounding the epithelium, in particular mesenchymal cells, are of primary importance in morphogenesis of this portion. The organ specificity of the development of the oral and esophageal epithelium is due to their local peculiarities.

Epithelium↗
PubMed1988

Regulation of lymphocyte homing. I. Alterations in homing receptor expression and organ-specific high endothelial venule binding of lymphocytes upon activation.

Upon activation, lymphocytes display profound alterations in their in vivo migration behavior. In an attempt to understand some of the cellular mechanisms responsible for this altered behavior, in vitro stimulated lymphocytes have been analyzed for their expression of a putative homing receptor (HOR) (defined by mAb MEL-14) and for their ability to bind to specialized lymphoid organ high endothelial venules (HEV) in vitro. The results indicate that signals related to lymphocyte activation induce complex alterations in HOR expression and organ-specificity of HEV-binding: 1) submitogenic stimuli induce an increase in MEL-14 antigen expression. This applies to almost all lymphocytes in autologous cultures, for the fraction of cells in periodate, LPS- or Con A-treated cultures not fully activated and for cultures stimulated with suboptimal doses of Con A. 2) Full blast transformation is associated with a decrease or complete loss of MEL-14 antigen expression on the majority of blasts in all activating systems used, but a subset of up to 30 to 40% of fully activated cells may nonetheless express very high levels of the MEL-14 antigen. 3) Functional assays reveal that Con A and periodate stimulation lead to a selective, nearly complete suppression of the lymphocytes binding to HEV of Peyer's patches, even under conditions where overall binding to peripheral node HEV is increased. This indicates a differential regulation of the two respective receptors, with the mucosa system-specific HOR being more prone to down-regulation during in vitro activation by these mitogens.

Animals↗
PubMed2006

Expression analysis of the sunflower SF21 gene family reveals multiple alternative and organ-specific splicing of transcripts.

The SF21 proteins were originally identified in sunflower pollen and in the stigmatic and transmitting tissues of sunflower pistils [Kräuter-Canham, R., Bronner, R., Evrard, J.L., Hahne, G., Friedt, W. and Steinmetz, A., 1997. A transmitting tissue- and pollen-expressed protein from sunflower with sequence similarity to the human RTP protein. Plant Science 129, 191-202.]. They are polypeptides of about 350 amino acids showing limited but significant sequence similarities with the animal NDR/RTP family of proteins of yet unknown function. Based on genomic sequence information derived from BAC clones containing SF21-related sequences we have identified transcripts generated from three different, but highly related genomic copies: SF21C, SF21D and SF21E. A sequence analysis of SF21C transcripts amplified by RT-PCR using specific primer pairs revealed a complex splicing pattern producing a minimum of three splice variant forms of the protein, one of 355 residues, and two truncated proteins of 90 and 138 amino acids, respectively. One of these variants was detected only in styles from pollinated florets, indicating organ-specific splicing. Two other splice variants, identified for a related transcript, SF21D, generate proteins differing by an 8-residue extension at their C-terminus. This analysis of SF21 transcripts in sunflower supports already existing evidence that alternative splicing is complex and common in plants.

Alternative Splicing↗
PubMed2003

Organ-specific overexpression of renal LAT2 and enhanced tubular L-DOPA uptake precede the onset of hypertension.

Spontaneously hypertensive rats (SHR) might have increased renal production of dopamine. L-3,4-Dihydroxyphenylalanine (L-DOPA) uptake in renal epithelial cells is promoted through the type 2 L-type amino acid transporter (LAT2), and this might rate-limit the synthesis of renal dopamine. The present study evaluated L-DOPA uptake in isolated renal proximal tubules of SHR and normotensive controls (Wistar-Kyoto rats [WKY]). Expression of LAT1 and LAT2 in the renal cortex and intestinal mucosa was also evaluated. Tubular uptake of L-DOPA in WKY and SHR was a saturable process, being greater in the latter than the former at both 4 and 12 weeks of age. cDNA fragments (LAT1, 688 bp; LAT2, 729 bp) labeled with 32P were used as probes for Northern blot analysis. Expression of LAT2 in SHR kidneys was higher than in WKY kidneys. This increase was more marked at 4 than at 12 weeks of age. Intestinal LAT2 expression, however, was identical in SHR and WKY at both 4 and 12 week of age. By Northern blot analysis, the LAT1 transcript was not identified in either the kidney or intestine. Kidney total RNA was then reverse-transcribed and amplified by polymerase chain reaction with specific primers for LAT1. The presence of a fragment of the expected size for LAT1 led to the conclusion that LAT1 mRNA is a rare message in kidney. We conclude that overexpression of LAT2 in the SHR kidney might contribute to the enhanced L-DOPA uptake, which is organ specific and precedes the onset of hypertension.

Amino Acid Transport System y+↗
PubMed2006

Identification of organ-specific T cell populations by analysis of multiparameter flow cytometry data using DNA-chip analysis software.

BACKGROUND: The analysis of cells from multiple experimental groups by multiparameter flow cytometry leads to the generation of complex data sets, for which adequate analysis tools are not commonly available. We report here that software designed for transcriptomics applications can be used in multiparameter flow cytometry. METHODS: Lymphocytes isolated from nine different mouse organs were stained and subjected to 10-parameter flow cytometry. The resulting data set contained 594 different T cell subsets per organ per mouse and was organized into a so-called flow cytometry array (FCA). RESULTS: Computation of a hierarchical tree revealed that lymph nodes and spleen were populated by similar T cell subsets, while T cells from peripheral organs displayed a diverse subset composition. Furthermore, organ-specific T cell subsets were identified. CONCLUSIONS: This new FCA concept in flow cytomics proved to be a valuable tool for the fast and unbiased analysis of complex multiparameter flow cytometry data sets. It can be used for assessing disease progression and therapeutic intervention, and for the association of disease-related biomarkers on the protein level.

Animals↗
PubMed1989

Investigations on organ-specific metabolism and genotoxic effects of the urinary bladder carcinogen N-nitrosobutyl-3-carboxypropylamine (BCPN) and its analogs N-nitrosodibutylamine (NDBA) and N-nitrosobutyl-4-hydroxybutylamine (4-OH-NDBA).

N-Nitrosodibutylamine (NDBA) and its omega-oxidized metabolites N-nitrosobutyl-4-hydroxybutylamine (4-OH-NDBA) and N-nitrosobutyl-3-carboxypropylamine (BCPN) are potent urinary bladder carcinogens. To study putative organ specific activation of BCPN, its alpha-oxidation by liver and urinary bladder microsomal fractions was investigated in comparison to NDBA and 4-OH-NDBA. Additionally, induction of DNA single strand breaks (SSB) was monitored in hepatocytes and in a human lymphoblastoid cell line (Namalva) in the presence and absence of external metabolic activation, including N-nitroso-t-butyl-n-butylamine as a negative control. BCPN was alpha-hydroxylated and dealkylated at both alkyl chains in small rates (about 1 nmol x mg protein-1 x 60 min-1) by microsomes from rat liver and pig urinary bladder epithelium. NDBA and 4-OH-NDBA were dealkylated at similarly low rates by pig urinary bladder microsomes, in strong contrast to the high debutylation rates observed for rat liver microsomes. Correspondingly, SSB induction by NDBA and 4-OH-NDBA was observed in Namalva cells with NDBA and 4-OH-NDBA in the presence of PB-induced rat liver microsomes but not with urinary bladder microsomes or without external activation. BCPN did not induce DNA-damage in Namalva cells (with or without external activation) or in rat hepatocytes. Significant induction of sister chromatid exchanges (SCEs) and micronuclei, however, was observed in Namalva cells after incubation with NDBA and BCPN. Our data suggest activation of BCPN via alpha-oxidation in the urinary bladder, even though activation rate in-vitro is so low that a positive response is not detectable by several short-term tests.

Animals↗
PubMed1983

Organ-specific difference in the sugar chains of gamma-glutamyltranspeptidase.

Sugar chains of gamma-glutamyltranspeptidase purified from neonatal mouse liver and adult mouse kidney were quantitatively released as oligosaccharides from the polypeptide backbone by hydrazinolysis. A comparative study of the structures of the oligosaccharides has revealed that the GlcNAc beta 1 leads to 4Man beta 1 leads to group is found in the sugar chains of kidney enzyme but not in those of liver enzyme. This is considered as an organ-specific difference common to mammals because the same phenomenon was found in bovine and rat enzymes.

Acyltransferases↗