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PubMed1997

Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: no alteration in adipose tissue of obese and NIDDM patients.

Members of the peroxisome proliferator-activated receptor (PPAR) family might be involved in pathologies with altered lipid metabolism. They participate in the control of the expression of genes involved in lipid metabolism and adipocyte differentiation. In addition, thiazolidinediones improve insulin resistance in vivo by activating PPAR gamma. However, little is known regarding their tissue distribution and relative expression in humans. Using a quantitative and sensitive reverse transcription (RT)-competitive polymerase chain reaction (PCR) assay, we determined the distribution and relative mRNA expression of the four PPARs (alpha,beta, gamma1, and gamma2) and liver X receptor-alpha (LXR alpha) in the main tissues implicated in lipid metabolism. PPAR alpha and LXR alpha were mainly expressed in liver, while PPAR gamma1 predominated in adipose tissue and large intestine. We found that PPAR gamma2 mRNA was a minor isoform, even in adipose tissue, thus causing question of its role in humans. PPAR beta mRNA was present in all the tissues tested at low levels. In addition, PPAR gamma mRNA was barely detectable in skeletal muscle, suggesting that improvement of insulin resistance with thiazolidinediones may not result from a direct effect of these agents on PPAR gamma in muscle. Obesity and NIDDM were not associated with change in PPARs and LXR alpha expression in adipose tissue. The mRNA levels of PPAR gamma1, the predominant form in adipocytes, did not correlate with BMI, leptin mRNA levels, or fasting insulinemia in 29 subjects with various degrees of obesity. These results indicated that obesity is not associated with alteration in PPAR gene expression in abdominal subcutaneous adipose tissue in humans.

Adipocytes↗

PubMed2003

Tissue distribution of prolactin receptor mRNA during late stage embryogenesis of the chick.

Serum prolactin increases during late embryogenesis. In order to elucidate the function of prolactin at this period, tissue distribution of prolactin receptor mRNA was examined by RNase protection assay. The mRNA was detected strongly in the kidney, intestine, and allantoic membrane; weakly detected in the brain; but not detected in the liver. The expression levels of the prolactin receptor mRNA in the kidney, intestine, and allantoic membrane were retained at constant levels during later stages of embryogenesis (Days 17 and 19) and posthatch periods (2 and 28 d after hatching). These results suggest that prolactin is mainly involved in the osmoregulation during the later stage of embryogenesis and that the expression of prolactin receptor mRNA in the kidney, intestine, and allantoic membrane is regulated by a serum prolactin-independent manner.

Allantois↗

PubMed1985

A short computer program for calculating tissue distributions in tumour-bearing nude mice after administration of radiolabelled specific and non-specific antibodies.

The short computer program described provides for rapid calculation of tumour and normal tissue distribution data for radiolabelled specific antibody and non-specific immunoglobulin in the nude mouse xenograft model. Results are displayed in convenient tabular form and also as a bar graph. Facilities for providing a hard copy of all results are installed within the program.

Animals↗

PubMed1992

Tissue distribution of MHC class II--positive cells, their down-manipulation by monoclonal antibodies and potential role in organ allograft immunogenicity.

This review article presents current state of knowledge of tissue distribution of MHC class II antigens in rat kidney. Our attention focuses particularly on down manipulation of these antigens by monoclonal antibodies. The results of organ perfusion procedure on prolongation of graft survival and perspectives of further studies are also discussed.

Animals↗

PubMed2002

Tissue distribution of Diablo/Smac revealed by monoclonal antibodies.

Diablo/Smac is a mammalian pro-apoptotic protein that can antagonize the inhibitor of apoptosis proteins (IAPs). We have produced monoclonal antibodies specific for Diablo and have used these to examine its tissue distribution and subcellular localization in healthy and apoptotic cells. Diablo could be detected in a wide range of mouse tissues including liver, kidney, lung, intestine, pancreas and testes by Western blot analysis. Immunohistochemical analysis found Diablo to be most abundant in the germinal cells of the testes, the parenchymal cells of the liver and the tubule cells of the kidney. In support of previous subcellular localization analysis, Diablo was present within the mitochondria of healthy cells, but released into the cytosol following the induction of apoptosis by UV.

3T3 Cells↗

PubMed2003

Tissue distribution of liposome-mediated epidermal growth factor receptor antisense gene therapy.

Despite the widespread use of liposome-mediated gene transfer in cancer therapy protocols, little is known about the tissue distribution of intralesionally administered DNA. We have previously shown that antisense gene therapy targeting the epidermal growth factor receptor (EGFR) inhibited tumor growth in a human head and neck squamous cell carcinoma (HNSCC) xenograft model. Further investigation demonstrated lack of systemic toxicity with intramuscular or intratumoral administration of this liposomal-DNA complex. In the present study, we compared two approaches to determine the presence of exogenous DNA in the plasma and tissues of mice treated with intramuscular injection of EGFR antisense gene therapy. PCR analysis using genomic DNA plus plasmid DNA as template was 83-fold more sensitive than PCR using a mixture of total RNA and plasmid DNA as template. With the more sensitive method (able to detect fewer than 500 molecules of EGFR antisense DNA in 1 microg of genomic DNA), foreign DNA was detected in all organs up to 1 month following a single injection. In contrast, using RNA plus plasmid DNA as template, exogenous DNA was only detected at the injection site at 1 week, and was undetectable at 1 month. Optical imaging studies demonstrated plasmid DNA only at the injection site. Although less sensitive than PCCR, Southern blot hybridization showed no evidence of integration of foreign DNA into the host genome in vitro or in vivo. These results emphasize the importance of defining the assays used to detect foreign DNA and suggest that the ability to detect intralesionally administered liposomal gene therapy, in organs distant from the injection site, is directly correlated with the sensitivity of the method employed.

Animals↗

PubMed1996

Two synpatic vesicle proteins of 25 kDa: a comparison of the molecular properties and tissue distribution of svp25 and o-rab3.

Two synaptic vesicle proteins of the electric ray Torpedo--svp25 and o-rab3--are compared with respect to their biochemical properties and tissue distribution. On SDS-PAGE both proteins migrate to the same position of about 25 kDa. As revealed by application of monospecific antibodies and subcellular fractionation both proteins comigrate and cofractionate with the synaptic vesicle compartment. o-Rab3 and svp25 can be separated by lectin chromatography; svp25 is highly glycosylated and binds to concanavalin A sepharose. Upon deglycosylation using glycopeptidase F and O-glycosidase its apparent molecular mass is reduced to about 14 kDa. Partial amino acid sequences obtained by direct microsequencing of purified and deglycosylated svp25 revealed that svp25 is a novel protein that has not yet been characterized in molecular terms. Whereas svp25 was detected in all brain areas investigated, the expression of o-rab3 was found to be restricted to specific regions. An immunoblot analysis demonstrates an exclusive association of both proteins with neural tissues. Our results suggest that cholinergic synaptic vesicles from electric ray electric organ contain at least two membrane-associated proteins of an apparent molecular mass of 25 kDa, the membrane associated o-rab3 and the membrane integral protein svp25. The two proteins can be separated by lectin chromatography for assessment of their biochemical properties.

Animals↗

PubMed2005

Tissue distribution and induction of the rat multidrug resistance-associated proteins 5 and 6.

Multidrug resistance-associated proteins (Mrps) are ATP-dependent transporters which transport a wide variety of anionic and cationic compounds. The purpose of this study was to determine the tissue distribution of Mrp5 and 6 in male and female Sprague-Dawley rats in various tissues, and to investigate whether the expression is altered by cholestasis or administration of microsomal enzyme inducers (MEIs). These MEIs activate six different transcriptionally-mediated pathways, and their effects on Mrp5 and Mrp6 expression were determined. The effects of bile-duct ligation, a cholestasis model, on Mrp5 and 6 expression in male rats were quantified. Mrp5 had marked expression in adrenal gland, and moderate expression in cerebral cortex, cerebellum, and stomach. The MEIs polychlorinated biphenyl (PCB)126, phenobarbital, and PCB99 slightly repressed Mrp5, but no single class of receptor agonists induced or repressed Mrp5. Bile-duct ligation tended to increase Mrp5 expression, but was not statistically significant at a 3 day timepoint. Mrp6 expression was highest in intestine, liver, and kidney. Mrp6 was slightly repressed by phenobarbital, dexamethasone, and isoniazid, but no one class of receptor agonists induced or repressed Mrp6, and expression was also unchanged bile-duct ligation. In conclusion, Mrp5 in rats is most highly expressed in the adrenal gland, whereas Mrp6 is mainly expressed in excretory organs (liver, intestine, and kidney), suggesting markedly different functions. Hepatic mRNA levels of Mrp5 or Mrp6 do not seem to be coordinately regulated along with Phase I enzymes via receptor-mediated pathways, and are not part of the hepatoprotective upregulation of basolateral transporters that occurs during cholestasis.

Animals↗

PubMedDate not supplied

Tissue distribution, circulating half-life, and excretion of intravenously administered protamine sulfate.

Intravenous protamine reversal of heparin anticoagulation may cause adverse hemodynamic side effects, but little is known about protamine's tissue distribution, circulating half-life (t/2), and excretion. The latter were assessed by examining 125I Bolton-Hunter (125I BH) radiolabeled protamine kinetics in a rat model. Three groups were studied: Group I controls (n = 5) received intravenous 125I BH label alone; Group II (n = 10) received intravenous 125I BH radiolabeled protamine (0.15 mg/100 g); and Group III (n = 10) received intravenous heparin (15 IU/100 g) followed by intravenous 125I BH radiolabeled protamine (0.15 mg/100 g). Five animals in each group were killed at 3 min, and tissue radioactivity was quantitated. An additional five animals each in Groups II and III were followed up for 60 min to determine protamine's circulating t/2 and its renal excretion. The lungs, heart, and kidneys, compared with other organs, retained the most 125I BH radiolabeled protamine per gram tissue at 3 min. Retention of 125I BH radiolabeled protamine (Groups II & III) was greater (p < 0.05, Kruskal-Wallis) than control 125I BH label alone (Group I). Higher tissue 125I activity was observed in Group II than in Group III rats, suggesting that tissue retention of protamine was greater in the absence of prior heparin administration. Circulating t/2 was shorter (18 vs. 24 min) and urinary protamine 125I excretion was higher (34 vs. 24%) in Group III than in Group II, respectively, suggesting more rapid renal clearance of protamine in the presence of heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Evaluation of the efficacy of various chelating agents on urinary excretion and tissue distribution of vanadium in rats.

The effect of repeated intraperitoneal administration of Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid), ascorbic acid, deferoxamine (DFOA) or 2-mercaptosuccinic acid on urinary excretion and tissue distribution of vanadium was assessed in rats which had previously received 12 intraperitoneal injections of sodium metavanadate (1.84 mg/kg per injection) or vanadyl sulphate trihydrate (6.35 mg/kg per injection) during a 4-week period. Chelating agents were administered daily for 5 days at doses equal to one-eighth of their respective LDSO. Only Tiron significantly decreased the tissue concentration of vanadium, whereas DFOA and Tiron significantly enhanced the urinary excretion of vanadium after repeated parenteral administration of sodium metavanadate. Again, only Tiron significantly increased the urinary elimination of vanadium following vanadyl sulphate administration. The results of this study show that Tiron has potential beneficial effects in the treatment of repeated intraperitoneal vanadium poisoning, while the effectiveness of DFOA is very uncertain. 2-Mercaptosuccinic and ascorbic acids were not effective as antidotes for parenteral vanadium intoxication.

Animals↗

PubMed1978

Ontogenic development and tissue distribution of renal proximal tubule brush border membrane antigens in the dog.

Using an antibody raised against highly purified dog renal proximal tubule brush border membranes, we have investigated the tissue distribution and ontogenic development of antigens sharing specificity with those in the renal brush border membrane. The antigens have been found in the small intestine, gall bladder, epididymis, pancreas, salivary gland, lacrimal gland, liver and spleen. Examination of embryos at various stages of gestation has revealed that the antigens make their appearance early in organogenesis, and are present in the cytoplasm as well as on the membrane during foetal development. Absorption studies have shown that at least two populations of antigens are present in the kidney: one appears to be kidney-specific and the other is shared by many epithelia. Maltase has been identified as one of the shared antigens.

Animals↗

PubMed2003

Local carboplatin delivery and tissue distribution in livers after radiofrequency ablation.

This study investigated the local drug pharmacokinetics of intralesional drug delivery after radiofrequency ablation of the liver. We hypothesized that the tissue architecture damaged by the ablation process facilitates the drug penetration in the liver and potentially enlarges the therapeutic margin in the local treatment of cancer. The delivery rate and tissue distribution of carboplatin, an anticancer agent, released from poly(D,L-lactide-co-glycolide) implants into rat livers after radiofrequency ablation were quantified by atomic absorption spectroscopy. Results showed that carboplatin clearance through blood perfusion was significantly slower in the ablated livers, leading to a more extensive tissue retention and distribution of the drug. The concentration of Pt at the implant-tissue interface ranged from 234 to 1440 microg Pt/(g liver) in the ablated livers over 144 h versus 56 to 177 microg Pt/(g liver) in the normal tissue. The maximum penetration distance at which Pt level reached above 6 microg/g (calculated based on a reported IC90 value for carboplatin) was 8-10 mm and 4-6 mm in ablated and normal liver, respectively. Histological analysis of the necrotic lesions showed widespread destruction of tissue structure and vasculature, supporting the initial hypothesis. This study demonstrated that intralesional drug delivery could provide a sustained, elevated concentration of anticancer drug at the ablation boundary that has the potential to eliminate residual cancer cells surviving radiofrequency ablation.

Animals↗

PubMed1980

H 9/25 monoclonal antibody recognizes a new allospecificity of mouse lymphocyte subpopulations: strain and tissue distribution.

C3 H/He-mg mice were immunized with C57BL/10 (B10) spleen cells and the immune spleen cells were fused with BALB/c myeloma cells (NS1). One of the monoclonal antibodies (H9/25 antibody) produced by the hybrid cells was studied. It reacts with subpopulations of B10 lymphocytes as well as some lymphoid tumor lines including some of the Abelson virus-induced leukemias. The antigen recognized by H9/25 antibody is expressed on lymphocytes from all the B10 congeneic mice tested as well as some other strains of mice. No linkage between genes coding for the antigen and H-2 loci was found as judged by its presence on cells of the B10 strains regardless of H-2 type and the distribution of the antigen on Bailey recombinant inbred mice. The antigen is expressed on subpopulations of lymph node cells, spleen cells, thymocytes and bone marrow cells. The strain distribution of the H9/25 antigen seems to be identical to that of Ly-6, Ly-8 and Ala-1 antigens. However, the tissue distribution of the antigen recognized by H9/25 antibody, while similar to these alloantigens, is unique and the antigen may be distinct from the other alloantigens.

Animals↗

PubMed2004

A predominant role of acyl-CoA:monoacylglycerol acyltransferase-2 in dietary fat absorption implicated by tissue distribution, subcellular localization, and up-regulation by high fat diet.

Acyl-CoA:monoacylglycerol acyltransferase-2 (MGAT2) catalyzes the synthesis of diacylglycerol and differs from the MGAT1 and MGAT3 in tissue distribution at the mRNA level. In addition to the small intestine, MGAT2 mRNA is also expressed at high levels in human liver, the lower gastrointestinal tract, and the mouse kidney, but the physiological significance of such expression has not yet been studied. Using an affinity-purified antibody, the present study investigated the expression of murine MGAT2 protein along the intestinal tract, determined its subcellular localization, and studied its regulation by diet and in db/db mouse. Results demonstrate a high level of MGAT2 expression in the small intestine in a proximal-to-distal gradient that correlated well with both MGAT enzyme activity and fat absorption pattern. In contrast, MGAT2 protein was not detectable in other sections of the digestive tract, including stomach, cecum, colon, and rectum, or other mouse tissues such as kidney, liver, and adipocytes. Immunohistological studies provided direct evidence that the enzyme is expressed not only in the villi, but also in the crypt regions of the small intestine, which suggests that MGAT2 expression occurs prior to the maturation of enterocytes. MGAT2 is localized in the endoplasmic reticulum (ER) in both MGAT2-transfected COS-7 and Caco-2 cells, indicating that the ER is the primary site for dietary fat re-synthesis. MGAT2 expression appeared not to be affected by diabetes in the db/db mouse, however, the total intestinal MGAT activity was significantly enhanced. Finally, an up-regulation of both MGAT2 protein expression and MGAT activity was observed in mice fed a high fat diet, implicating a role of MGAT2 in diet-induced obesity. Taken together, our data suggest a predominant role of MGAT2 in dietary fat absorption.

Acyltransferases↗

PubMed1992

Insulin-like growth factor binding protein (IGFBP)4 accounts for the connective tissue distribution of endothelial cell IGFBPs perfused through the isolated heart.

Insulin-like growth factor binding protein 4 (IGFBP4) was purified to homogeneity from conditioned media of bovine pulmonary artery endothelial cells and shown to have the N-terminal amino acid sequence DEAIHCPPCS, a sequence unique to IGFBP4. The IGFBP4 was separated into predominantly glycosylated and nonglycosylated fractions, with each fraction separately perfused through isolated, beating rat hearts. Both forms of IGFBP4 crossed the capillary boundary of the heart and distributed primarily in subendothelial connective tissue components with a connective tissue/cardiac muscle distribution ratio of 20:1 for the glycosylated fraction and 27:1 for the nonglycosylated fraction. Perfused IGFBP1, 2, 3, and IGF-I also crossed the capillary boundary but in contrast to IGFBP4, preferentially localized in cardiac muscle with a connective tissue/muscle ratio of approximately 1:3. We conclude that the connective tissue distribution previously reported for IGFBPs in conditioned media of pulmonary artery endothelial cells is due to IGFBP4.

Amino Acid Sequence↗

PubMed1997

Tissue distribution and general safety of MnDPDP in male beagle dogs, with or without total common bile duct obstruction.

PURPOSE: Evaluation of the tissue distribution of manganese (Mn) and general safety in normal and cholestatic male beagle dogs after i.v. administration of mangafodipir trisodium (MnDPDP, Teslascan). MATERIAL AND METHODS: Male beagle dogs, with or without surgical obstruction of the common bile duct, received a single i.v. bolus injection of saline (control), or MnDPDP at doses of 10 or 50 mumol/kg b.w. and were sacrificed 1 or 7 days after treatment. Toxicity was assessed and tissue concentrations of Mn were measured. RESULTS: Increased tissue Mn concentrations were found in all dogs treated with MnDPDP and were greatest in those with biliary obstruction. Although Mn concentrations decreased with time in most tissues in each of the treated groups, this was not the case for the brain and adrenal glands in dogs with total biliary obstruction in which further increases in Mn concentrations were seen at the later time point. This suggested a re-distribution of Mn from the major body depots such as the liver. There were no effects of MnDPDP on clinical signs/behaviour, organ weights, histomorphology or clinical biochemistry. CONCLUSION: These findings indicate that a single clinical dose of 5 mumol/kg MnDPDP is likely to be well tolerated in patients with cholestasis.

Animals↗

PubMed1987

Tissue distribution of insulin-like growth factor I and II messenger ribonucleic acid in the adult rat.

The insulin-like growth factors (IGFs) have both metabolic and growth-promoting activities in many cell and tissue types. Although the IGFs are present in serum, they are also thought to have important autocrine and paracrine functions. Using complementary DNA (cDNA) probes for rat IGF-I and mouse IGF-II, we have investigated the tissue distribution of messenger RNAs (mRNAs) for these growth factors in adult rats. IGF-I cDNA hybridized with three groups of transcripts, 7.0, 1.8 and 0.7-1.1 kilobases, which were detectable in all tissues examined, with liver demonstrating the highest level of expression. IGF-II cDNA also hybridized to a number of mRNAs, the most abundant of which was 4.0 kilobases. Of the tissues examined, IGF-II expression was highest in the brain, barely detectable in the liver, and undetectable under the conditions used, in lung, ovary, testes, and mammary gland. These studies support the notion of paracrine or autocrine function for IGF-I and demonstrate tissue-specific IGF-II expression in the adult rat.

Animals↗

PubMed1997

Tissue distribution of Na+/H+ exchanger isoforms NHE2 and NHE4 in rat intestine and kidney.

We present evidence that tissue distribution of two highly conserved Na+/H+ exchanger isoforms, NHE2 and NHE4, differs significantly from previously published reports. Riboprobes unique to each of these antiporters, from 5' (noncoding and coding) and 3' coding regions, were used to analyze mRNA from adult rat kidney and intestine by ribonuclease protection assay and in situ hybridization. In contrast to earlier work that concluded that both NHE2 and NHE4 were expressed throughout the intestine and in the kidney, our data show that there is no NHE2 message in the kidney and NHE4 is not expressed in small or large intestine. Analyses of intestinal epithelial and kidney membrane proteins by an NHE2-specific antibody identified a doublet at < 90 kDa in intestine but not in kidney. NHE2 is highly expressed in the Na(+)-absorptive epithelium of jejunum, ileum, and ascending and descending colon. NHE4 mRNA message is found in the inner medulla of the kidney as previously reported (C. Bookstein, M. W. Musch, A. DePaoli, Y. Xie, M. Villereal, M. C. Rao, and E. B. Chang. J. Biol. Chem. 269: 29704-29709, 1994) and not in the intestine. From these data, we speculate that neither NHE2 nor NHE4 has a role in renal Na+ absorption. NHE2 is likely involved in gut Na+ absorption, whereas NHE4 may have a specialized role in cell volume rectification of inner medullary collecting duct cells. Knowledge of the correct tissue and cell-specific distribution of these two antiporters should help significantly in understanding their physiological roles.

Animals↗