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Results for “tissue differentiation”

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At least 235 records · Page 13Linked to original sources
PubMed1998

Teratogen-induced cell death in postimplantation mouse embryos: differential tissue sensitivity and hallmarks of apoptosis.

Teratogen-induced cell death is a common event in the pathogenesis associated with tissues destined to be malformed. Although the importance of this cell death is recognized, little information is available concerning the biochemistry of teratogen-induced cell death. We show that three teratogens, hyperthermia, cyclophosphamide and sodium arsenite induce an increase in cell death in day 9.0 mouse embryos with concurrent induction of DNA fragmentation, activation of caspase-3 and the cleavage of poly (ADP-ribose) polymerase (PARP). Teratogen-induced cell death is also selective, i. e., some cells within a tissue die while others survive. In addition, cells within some tissues die when exposed to teratogens while cells in other tissues are relatively resistant to teratogen-induced cell death. An example of the latter selectivity is seen in the cells of the developing heart, which are resistant to the cytotoxic potential of many teratogens. We show that the absence of cell death in the heart is accompanied by the complete lack of DNA fragmentation, activtion of caspase-3 and the cleavage of PARP.

Animals↗
PubMed1986

Differential tissue expression of the glutathione transferase multigene family.

The content of GSH transferase mRNAs in poly(A)-containing RNA isolated from eight rat tissues was examined by immunoprecipitation of cell-free translation products and by Northern blotting. Considerable tissue-specific distribution and heterogeneity of immunoprecipitable GSH transferase subunits 1 and 2 synthesized in vitro was observed. These results were confirmed by Northern blotting using a 32P-labelled subunit 1 cDNA probe. The same probe, used in a Southern blot analysis of genomic DNA, provided confirmation that GSH transferase subunits 1 and 2 comprise a multigenic family in the rat. The results show that the selection of cDNA clones coding for chosen subunits can be made easier by making use of qualitative and quantitative tissue differences in GSH transferase mRNAs.

Animals↗
PubMed2003

Differential tissue and enzyme inhibitory effects of the vasopeptidase inhibitor omapatrilat in the rat.

Vasopeptidase inhibitors simultaneously inhibit angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The present study characterized the tissue distributions of ACE and NEP, and assessed the effects of the vasopeptidase inhibitor omapatrilat on ACE and NEP in rat tissues. In vivo ACE and NEP inhibition was studied by in vitro autoradiography and using the ACE inhibitor radioligand (125)I-MK351A and the NEP inhibitor radioligand (125)I-RB104 in rats that received oral omapatrilat (40 mg x day(-1) x kg(-1)) for 3 days. In vitro autoradiography was used to examine the distribution of ACE and NEP in the kidney, aorta, heart, adrenal gland, lung, intestine, liver, spleen and brain, and to assess enzyme inhibition after oral omapatrilat. Omapatrilat inhibited plasma ACE and increased plasma renin activity (P <0.01). Tissue ACE was inhibited by 70-95% (P <0.01), except in the brain, where ACE was not inhibited. NEP was inhibited by 87% in the kidney and by 20-40% in atria, aorta, adrenal gland, lung, liver and intestine; it was not inhibited in the brain, the ventricle or the spleen. Omapatrilat is a potent vasopeptidase inhibitor that significantly inhibits tissue ACE and NEP, with the degree of inhibition varying according to the enzyme and the tissue under assessment. The degree and site of tissue enzyme inhibition by vasopeptidase inhibitors may be relevant to end-organ protection as well as to the side-effect profiles of these agents.

Administration, Oral↗
PubMed2002

Differential tissue targeting and pathogenesis of verotoxins 1 and 2 in the mouse animal model.

BACKGROUND: Both verotoxin (VT)1 and VT2 share the same receptor, globotriaosyl ceramide (Gb(3)). Although VT1 is slightly more cytotoxic in vitro and binds Gb(3) with higher affinity, VT2 is more toxic in mice and may be associated with greater pathology in human infections. In this study we have compared the biodistribution of iodine 125 ((125)I)-VT1 and (125)I-VT2 versus pathology in the mouse. METHODS: (125)I-VT1 whole-body autoradiography defined the tissues targeted. VT1 and VT2 tissue distribution, clearance, and tissue binding sites were compared. The effect of a soluble receptor analogue, adamantylGb(3), on VT2/Gb3 binding and in vivo pathology was assessed. RESULTS: (125)I-VT1 autoradiography identified the lungs and nasal turbinates as major, previously unrecognized, targets, while kidney cortex and the bone marrow of the spine, long bones, and ribs were also significant targets. VT2 did not target the lung, but accumulated in the kidney to a greater extent than VT1. The serum half-life of VT1 was 2.7 minutes with 90% clearance at 5 minutes, while that of VT2 was 3.9 minutes with only 40% clearance at 5 minutes. The extensive binding of VT1, but not VT2, within the lung correlated with induced lung disease. Extensive hemorrhage into alveoli, edema, alveolitis and neutrophil margination was seen only after VT1 treatment. VT1 targeted lung capillary endothelial cells. Identical tissue binding sites (subsets of proximal/distal tubules and collecting ducts) for VT1 and VT2 were detected by toxin overlay of serial frozen kidney sections. Glucosuria was found to be a new marker of VT1- and VT2-induced renal pathology and positive predictor of outcome in the mouse, consistent with VT-staining of proximal tubules. Lung Gb3 migrated on thin-layer chromatography (TLC) faster than kidney Gb(3), suggesting a different lipid composition. AdamantylGb(3), a soluble Gb(3) analogue, competed effectively for Gb3 binding by VT1 and VT2 in vitro. However, the effect in the mouse model (only measured against VT2, due to the lower LD(50), a concentration required for 50% lethality) was to increase, rather than reduce, pathology and further reduce the VT2 serum clearance rate. Additional renal pathology was seen in VT2 + adamantylGb(3)-treated mice. CONCLUSIONS: The lung is a preferential (Gb(3)) "sink" for VT1, which explains the relatively slower clearance of VT2 and subsequent increased VT2 renal targeting and VT2 mortality in this animal model.

Animals↗
PubMed1991

Differential tissue localization of oviduct and erythroid transferrin receptors.

The tissue distributions of the estrogen-inducible hen oviduct transferrin receptor and the chicken embryonic erythrocyte transferrin receptor were studied. Tissue sections were investigated by immunofluorescence microscopy using specific polyclonal antisera against each receptor. The receptor originally identified and characterized in the oviduct strongly stained liver and ovary; localized staining was observed in the brain (especially endothelial cells). Staining of breast muscle and heart tissue occurred only in occasional interstitial cells. Antiserum against oviduct transferrin receptor did not stain erythrocytes, either from embryos or from mature animals. On the other hand, the antiserum directed against the embryonic erythrocyte receptor stained embryonic erythrocytes; it did not stain any other tissues. The fluorescence microscopy observations were confirmed by Western blot analysis. The strong staining of oviduct, liver, and ovary suggests a major role for the oviduct transferrin receptor in oogenesis.

Animals↗
PubMedDate not supplied

A quantitative study of blood capillary formation (angiogenesis) concomitant with parenchymal tissue differentiation.

Examination of the rat corpus luteum (CL) provided quantitative data supporting adaptation of the developing vasculature to maximise efficient acceptance of steroids secreted from the luteal cells. Numbers of endothelial cells (ECs) significantly increased during the initial formation of the CL, followed by a further significant proliferation from day 10 to day 16 when there was maximal growth of the CL. As a consequence, there was significant growth of the vascular compartment during this time interval. The final phase of expanding endothelium (days 10 to 16) was a result of increased ECs volume with elongation of the EC in the direction of growth. Continued increase in capillary surface area and a corresponding marked reduction in diffusion distance between LC and ECs evidenced adaptation of the developing microvasculature to enable efficient endocrine function by day 16, when steroid secretion is maximal. Furthermore, from day 1 to day 3 there was close apposition of pericytes to the endothelium, suggesting the important role of pericytes in the initiation of angiogenesis. However, this degree of association was reduced from day 10 to day 16 and was a consequence of expansion of the EC cytoplasm to provide a greater surface area for transport of steroids.

Animals↗
PubMed2004

The differential tissue distribution of the citrus flavanone naringenin following gastric instillation.

Citrus flavonoids have been investigated for their biological activity, with both anti-inflammatory and -carcinogenic effects being reported. However, little information is known on the bioavailability of these compounds in vivo. The objectives of this study were to determine the tissue distribution of naringenin after gastric gavage of [3H]-naringenin to rats. Unlabelled naringenin was also used to quantify the levels of naringenin and its major metabolites in tissues and eliminated in the urine and faeces. Significant radioactivity was detected in the plasma as well as all tissues examined 2h post-gavage. After 18h, higher levels of radioactivity were retained in plasma and tissues (55% of the administered radioactivity). Investigation of the nature of metabolites, using unlabelled naringenin, revealed that the glucuronides were the major components in plasma, tissues and urine, in addition to the colonic metabolite 3-(4-hydroxyphenyl) propionic acid, detected in the urine. The aglycone was the form extensively retained in tissues after 18h post-gavage. Total identified metabolites detected after 18h in most tissues were only 1-5% of the levels detected after 2h. However, the brain, lungs and heart retained 27, 20 and 11%, respectively, relative to the total metabolites detected at 2h. While radioactive detection suggests increased levels of breakdown products of naringenin after 18 h versus 2 h, the products identified using unlabelled naringenin are not consistent with this, suggesting that a predominant proportion of the naringenin breakdown products at 18 h are retained as smaller decomposition molecules which cannot yet be identified.

Animals↗
PubMed2004

Polyphyletic origin of pyrrolizidine alkaloids within the Asteraceae. Evidence from differential tissue expression of homospermidine synthase.

The evolution of pathways within plant secondary metabolism has been studied by using the pyrrolizidine alkaloids (PAs) as a model system. PAs are constitutively produced by plants as a defense against herbivores. The occurrence of PAs is restricted to certain unrelated families within the angiosperms. Homospermidine synthase (HSS), the first specific enzyme in the biosynthesis of the necine base moiety of PAs, was originally recruited from deoxyhypusine synthase, an enzyme involved in the posttranslational activation of the eukaryotic initiation factor 5A. Recently, this gene recruitment has been shown to have occurred several times independently within the angiosperms and even twice within the Asteraceae. Here, we demonstrate that, within these two PA-producing tribes of the Asteraceae, namely Senecioneae and Eupatorieae, HSS is expressed differently despite catalyzing the same step in PA biosynthesis. Within Eupatorium cannabinum, HSS is expressed uniformly in all cells of the root cortex parenchyma, but not within the endodermis and exodermis. Within Senecio vernalis, HSS expression has been previously identified in groups of specialized cells of the endodermis and the adjacent root cortex parenchyma. This expression pattern was confirmed for Senecio jacobaea as well. Furthermore, the expression of HSS in E. cannabinum is dependent on the development of the plant, suggesting a close linkage to plant growth.

Alkyl and Aryl Transferases↗
PubMed1990

Dominance of memory over naive T cells in contact dermatitis is due to differential tissue immigration.

CD4+ T cells include a naive (CD4-, CD45RO-, CD29-, CD45RA+) as well as a memory subpopulation (CD4+, CD45RO+, CD29+, CD45RA-). These subpopulations represent different stages in T-cell development and function. Recently, it has been shown that inflammatory and neoplastic CD4+ T-cell infiltrates are dominated by the memory subpopulation, whereas both subpopulations are about the same size in the peripheral blood. This was thought to be the result of in situ maturation of naive into memory T cells. We analysed early positive patch-test reactions 1-2 days after antigen challenge and found that most of the CD4+ T cells that had freshly immigrated into the tissue carried the memory phenotype. Their preferential migration may be mediated by at least five adhesion molecules expressed on their cell surface. This observation has important pathogenetic implications, since memory T cells can be rapidly activated by antigens and secrete a wide variety of pro-inflammatory cytokines.

Antigens, CD↗
PubMed2005

A novel glycogen-targeting subunit of protein phosphatase 1 that is regulated by insulin and shows differential tissue distribution in humans and rodents.

Stimulation of glycogen-targeted protein phosphatase 1 (PP1) activity by insulin contributes to the dephosphorylation and activation of hepatic glycogen synthase (GS) leading to an increase in glycogen synthesis. The glycogen-targeting subunits of PP1, GL and R5/PTG, are downregulated in the livers of diabetic rodents and restored by insulin treatment. We show here that the mammalian gene PPP1R3E encodes a novel glycogen-targeting subunit of PP1 that is expressed in rodent liver. The phosphatase activity associated with R3E is slightly higher than that associated with R5/PTG and it is downregulated in streptozotocin-induced diabetes by 60-70% and restored by insulin treatment. Surprisingly, although mRNA for R3E is most highly expressed in rat liver and heart muscle, with only low levels in skeletal muscle, R3E mRNA is most abundant in human skeletal muscle and heart tissues with barely detectable levels in human liver. This species-specific difference in R3E mRNA expression has similarities to the high level of expression of GL mRNA in human but not rodent skeletal muscle. The observations imply that the mechanisms by which insulin regulates glycogen synthesis in liver and skeletal muscle are different in rodents and humans.

Amino Acid Sequence↗
PubMedDate not supplied

Iterative method for elimination of the Kbeta filter in dual-beam differential tissue absorptiometry.

The application of a dual photon beam to the measurement of tissue and tissue-like substances has generally required the use of a filter to attain the required monochromaticity of the lower-energy x-ray photons. In many cases this has the undesirable effect of also severely attenuating the desired low-energy beam. A method for circumventing the use of the filter is described. The technique relies on a knowledge of the initial intensities of the components of the x-ray portion of the dual beam and involves an iterative mathematical procedure. Experimental verification of the method using both tissue and nontissue substances has been carried out. R values obtained with the iterative system show good correlation with filtered values.

Body Composition↗