SEARCH · PubMed Health

Results for “tissue specificity”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources

PubMed2004

Bacteriophage T7 RNA polymerase-directed, inducible and tissue-specific over-expression of foreign genes in transgenic plants.

A widely applicable bacteriophage T7 RNA polymerase-directed, tissue-specific and inducible over-expression of foreign genes in transgenic plants was developed. This was achieved through the simultaneous transformation of a modified T7 RNA polymerase to specifically transcribe the foreign gene placed under the control of T7 expression signals. The T7 RNA polymerase recognized the chimeric uidA gene integrated randomly into tobacco and rice genomes. Results from the use of six different promoters with different tissue specificities indicated that the recombinant protein was expressed at a several-fold (3-10-fold) higher level when compared with transgenes expressed directly under the control of these tissue-specific promoters. An important feature of the T7 system in plants was the near-uniform expression in the independently transformed plants, in contrast with the large variations observed in transgene expression under the direct control of plant promoters. In addition, our results demonstrated the application of the T7 system in the regulation of transgene expression through chemically inducible mechanisms. This versatility of controlled and regulated expression offers a powerful tool that could be used in various programmes in plant biotechnology and genomic studies.

Journal Article↗

PubMed1988

A novel serum assay for pancreatic cellular damage. II. High tissue specificity of a pancreatic protein.

A previously unknown major protein in human pancreatic cytosol has been purified and partly characterized. The protein, designated pancreas specific protein (PASP), has a molecular weight of 44,500 and a pI of 6.9. A two-dimensional gel separation technique revealed the protein to be specific for normal pancreatic tissue. Antibodies against PASP were raised in rabbits and a radioimmunoassay was developed for the quantitation of this protein. The following concentrations of PASP (mg/kg wet weight) were found in human tissues: normal pancreas 100-1,000; pancreatic carcinoma 0.1-20; prostate 0.5-5; and 13 other tissues less than 0.5. The levels of PASP in peripheral serum were less than 0.1 mg/L in normal subjects, 0.7-3 mg/L in cases of acute pancreatitis, and less than 0.1 mg/L in cases of pancreatic carcinoma, prostatic diseases, and other abdominal diseases investigated. The high tissue specificity and the specific elevation of serum PASP levels in acute pancreatitis may indicate a use of this protein as a marker of this pancreatic condition.

Biomarkers↗

PubMed2001

Tissue-specific gene expression in medullary thyroid carcinoma cells employing calcitonin regulatory elements and AAV vectors.

Calcitonin (CT), the major secretory product of the C cell, is also expressed in C-cell-derived neoplasia. To investigate the role of the CT gene regulatory sequence in tissue-specific gene expression, the genes coding for the herpes simplex virus thymidine kinase (HSVtk) and for the enhanced green fluorescent protein (EGFP) regulated by the CT promoter (rAAV/CT266tkneo), the CT promoter/enhancer element (rAAV/CTenhtkneo), or the cytomegalovirus (CMV) promoter (rAAV/CMVtkneo) were transduced by recombinant adenoassociated viral (AAV) vectors into the medullary thyroid carcinoma (MTC) cell lines TT and hMTC and into HeLa cells as controls. In TT cell lines and hMTC cell lines transiently infected by the rAAV/CT266tkneo viruses, a significant increase in (3)H ganciclovir uptake was observed. Upon ganciclovir treatment, TT cells infected by rAAV/CT266tkneo revealed a significant growth inhibition, which was less tissue-specific because HeLa cells were also affected by these particles (74.5%). In contrast, a minor but more tissue-specific growth inhibition (33.6%) was observed for TT cells after transient infection with the rAAV/CTenhtkneo particles. Employing EGFP controlled by CMV promoter and the individual CT regulatory sequences for transduction by rAAV particles, similar results were obtained indicating that both the CT promoter and enhancer element are required for tissue-specific gene expression in MTC.

Calcitonin↗

PubMed1998

Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex.

Tissue distribution and kinetic parameters for the four isoenzymes of pyruvate dehydrogenase kinase (PDK1, PDK2, PDK3 and PDK4) identified thus far in mammals were analysed. It appeared that expression of these isoenzymes occurs in a tissue-specific manner. The mRNA for isoenzyme PDK1 was found almost exclusively in rat heart. The mRNA for PDK3 was most abundantly expressed in rat testis. The message for PDK2 was present in all tissues tested but the level was low in spleen and lung. The mRNA for PDK4 was predominantly expressed in skeletal muscle and heart. The specific activities of the isoenzymes varied 25-fold, from 50nmol/min per mg for PDK2 to 1250nmol/min per mg for PDK3. Apparent Ki values of the isoenzymes for the synthetic analogue of pyruvate, dichloroacetate, varied 40-fold, from 0.2 mM for PDK2 to 8 mM for PDK3. The isoenzymes were also different with respect to their ability to respond to NADH and NADH plus acetyl-CoA. NADH alone stimulated the activities of PDK1 and PDK2 by 20 and 30% respectively. NADH plus acetyl-CoA activated these isoenzymes nearly 200 and 300%. Under comparable conditions, isoenzyme PDK3 was almost completely unresponsive to NADH, and NADH plus acetyl-CoA caused inhibition rather than activation. Isoenzyme PDK4 was activated almost 2-fold by NADH, but NADH plus acetyl-CoA did not activate above the level seen with NADH alone. These results provide the first evidence that the unique tissue distribution and kinetic characteristics of the isoenzymes of PDK are among the major factors responsible for tissue-specific regulation of the pyruvate dehydrogenase complex activity.

Acetyl Coenzyme A↗

PubMed1996

Tissue specificity of L-pyruvate kinase transgenes results from the combinatorial effect of proximal promoter and distal activator regions.

The L-type pyruvate kinase (L-PK) gene is regulated by diet and hormones and expressed at high levels in the hepatocytes, enterocytes, and proximal tubular cells of the kidney and at low levels in the endocrine pancreatic cells. Two regulatory regions have been shown to be important in transgenic mice to confer on a reporter gene a similar tissue-specific and diet-responsive expression: a proximal promoter fragment, with binding sites for the tissue-specific hepatocyte nuclear factors 1 and 4, and presence of the glucose-response element (GIRE) and a distal activator corresponding to a liver-specific hypersensitive site at -3000 bp with respect to the cap site. Although the proximal promoter is able to confer by itself tissue-specific expression on a reporter gene, its activity in vivo is strongly stimulated by the distal activator. To determine the possible role of the distal region on diet responsiveness and tissue specificity of the L-PK gene expression, we have created lines of transgenic mice in which the gene for SV40 T antigen (Tag) was directed by composite regulatory sequences consisting of the L-PK promoter and different enhancers: either the SV40 early enhancer (SV) or the H enhancer of the aldolase A gene (H). The induction of the composite H-PK/Tag and SV-PK/Tag transgenes by a carbohydrate-rich diet in the liver was similar to that of the endogenous L-PK gene. This suggests that in fasted mice the L-PK promoter, and especially the GIRE, is able to silence the activating influence of a strong viral enhancer such as the SV40 enhancer. The H-PK/Tag mice expressed the transgene similarly to the endogenous gene, except in the pancreas, where expression was practically undetectable. Consistently, whereas L-PK/Tag mice develop insulinomas, H-PK/Tag mice develop only hepatomas. In contrast, the transgene expression was partly aberrant in SV-PK/Tag mice. In addition to a normal activation of the transgene in the liver, a strong expression was also detected in the kidney medulla, whereas the transgene was practically silent in enterocytes. Finally, the effect of the distal region (-2070 to -3200) on an ubiquitous promoter was tested by ligating the distal L-PK gene fragment in front of a thymidine kinase/CAT transgene. Such a transgene was constantly expressed in the pancreas and, strikingly, in the brain. It appears, therefore, that the L-PK distal activator exhibits, by itself, a certain neuropancreatic specificity required in combination with the proximal promoter for L-PK gene expression in pancreas endocrine cells.

Animals↗

PubMed1997

Renal allograft infiltrating lymphocytes: frequency of tissue specific lymphocytes.

Acute rejection, mediated by T lymphocytes recognizing donor MHC class I and II, is a major factor influencing renal transplant survival. To define the specificity of these effector cells we examined cytolytic activity of graft infiltrating T lymphocytes (GIL) from renal biopsies of individuals undergoing acute cellular rejection. The majority of these cells recognized MHC class I on both donor kidney epithelial cells (KCL) and B-lymphoblastoid cells (LCL) suggesting these T cells recognized peptides from various tissues. However, cold target inhibition experiments demonstrated a significant proportion of GIL T cells were tissue specific. We reported previously that kidney specific CTL can be isolated from biopsies of kidney allografts undergoing acute cellular rejection. Here we extend that observation showing we were able to isolate tissue specific CTL from two additional biopsies. Greater than 10% of the clones isolated (4 of 36 and 5 of 37) from these biopsies were CTL recognizing donor KCL but not LCL targets suggesting that peptides, recognized in the context of donor MHC, were tissue specific. Repeated isolation of significant numbers of tissue specific CTL suggests these T cells play a role in allograft rejection and may be important effector cells mediating rejection in HLA matched transplants.

Adult↗

PubMed1997

Retrotransposon insertion into the maize waxy gene results in tissue-specific RNA processing.

We previously reported that three alleles of the maize waxy (wx) gene were alternatively spliced as a result of the insertion of retrotransposons into intronic sequences. In addition, inefficient splicing of element sequences with the surrounding intron produced wild-type transcripts that presumably were responsible for the observed residual gene expression in the endosperm. In this study, we report that one of these alleles, wxG, has a tissue-specific phenotype with 30-fold more WX enzymatic activity in pollen than in the endosperm. Quantification of wxG-encoded transcripts in pollen and the endosperm demonstrates that this difference can be accounted for by tissue-specific differences in RNA processing. Specifically, there is approximately 30-fold more correctly spliced RNA in pollen than in the endosperm. Based on an analogy to similar examples of tissue-specific alternative splicing in animal systems, we hypothesize that the tissue-specific phenotype of the wxG allele may reflect differences in the concentration of splicing factors in these tissues.

Alleles↗

PubMed2002

Modulation of tissue-specific immune response to cardiac myosin can prolong survival of allogeneic heart transplants.

The role of immune response to tissue-specific Ags in transplant rejection is poorly defined. We have previously reported that transplantation of cardiac allografts triggers a CD4(+) Th1 cell response to cardiac myosin (CM), a major contractile protein of the heart, and that pretransplant activation of proinflammatory CM-specific T cells accelerates rejection. In this study, we show that administration of CM together with IFA (CM/IFA) can prevent acute rejection of an allogeneic heart transplant. Prolongation of cardiac graft survival is associated with activation of CM- and allo-specific T cells secreting type 2 cytokines (IL-4, IL-5) and reduction of the frequency of proinflammatory IFN-gamma-secreting (type 1) alloreactive T cells. Blocking of IL-4 cytokine with Abs abrogates the prolongation. CM/IFA treatment prevents acute rejection of MHC class I-mismatched, but not fully mismatched grafts. However, if donor heart is devoid of MHC class II expression, CM-IFA administration delays rejection of fully allogeneic cardiac transplants. This finding suggests that the effect of CM modulation depends on the type (direct vs indirect) and strength of recipient's CD4(+) T cell alloresponse. Our results underscore the important role of host immunity to tissue-specific Ags in the rejection of an allograft. This study demonstrates that modulation of the immune response to a tissue-specific Ag can significantly prolong cardiac allograft survival, an observation that may have important implications for the development of novel selective immune therapies in transplantation.

Animals↗

PubMed1983

Identification of a human pancreatic duct tissue-specific antigen.

Antiserum raised against a pancreatic duct mucin was absorbed with type AB red blood cells and used in the indirect immuno-glucose oxidase procedure to examine tissue specificity. All mucin-producing organs were stained by this antiserum. Absorption of the antiserum with mucinous ovarian cystadenocarcinoma fluid eliminated generalized mucin staining, and only pancreatic ducts and colonic goblet cells were positive. Further absorption with purified colonic mucin revealed a pancreatic duct tissue-specific determinant(s). This tissue-specific determinant(s) was detected in the RIP-1 and RIP-2 human pancreatic adenocarcinomas carried as xenografts in athymic nude mice. Because the majority of pancreatic adenocarcinomas are believed to arise from ductal tissue, pancreatic duct mucin may have a useful role as a marker in detection and differential diagnosis.

Animals↗

PubMed2004

Exercise-induced tissue-specific change in gene expression of endothelin-1.

Exercise causes an integrated physiological response (e.g., an increase in cardiac output and a significant redistribution of tissue blood flow), which greatly increases blood flow in active muscles but decreases it in the splanchnic circulation. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular endothelial cells. We hypothesized that exercise causes a tissue-specific change in ET-1 production in various organs. We studied whether a bout of exercise alters the expression of preproET-1 mRNA in various tissues of rats. The rats were randomly divided into exercise rats and control rats. Exercise rats performed treadmill running for 30 minutes at a speed of 30 m/minute. Control rats remained at rest during the same period (30 minutes). Immediately after the exercise and rest, the abdominal artery, liver, muscles (tibialis anterior muscle, plantar muscle and soleus) and adipose tissue were quickly removed and the expression of preproET-1 mRNA in these tissues was determined by real-time quantitative polymerase chain reaction analysis. The expression of preproET-1 mRNA in these tissues was changed in a different manner by acute exercise (i.e., increased, decreased, or unchanged). The expression of preproET-1 mRNA in the aorta was significantly decreased by exercise, whereas that in the plantar muscle was significantly increased by exercise. There were no significant differences in the expression of preproET-1 mRNA in the liver, tibialis anterior muscle, soleus and adipose tissue between the exercise rats and the control rats. These results show that the expression of preproET-1 mRNA was changed tissue-specifically by acute exercise. We demonstrate that acute exercise causes tissue-specific changes in the production of ET-1 and that these alterations may participate in the integrated physiological response during exercise.

Adipose Tissue↗

PubMed2003

Tyrosinase-Cre mice for tissue-specific gene ablation in neural crest and neuroepithelial-derived tissues.

This study describes the derivation of two new lines of transgenic mice that express Cre recombinase under the control of tyrosinase transcriptional elements. To determine the suitability of the Tyrosinase-Cre transgene for tissue-specific gene ablation studies, a fate map of Cre expression domains was determined using the Z/AP reporter strain. It was shown that Cre-expressing cells contribute to a wide array of neural crest and neuroepithelial-derived lineages. The melanocytes of the harderian gland and eye choroid, sympathetic cephalic ganglia, leptomeninges of the telencephalon, as well as cranial nerves (V), (VII), and (IX) are derived either fully or partly from Cre-expressing cephalic crest. The cells contributing to the cranial nerves were the first to exhibit Cre expression at E10.5 as they were migrating into the branchial arches. The melanocytes, chromaffin cells of the adrenal medulla, and dorsal root ganglia are derived from trunk neural crest that either express Cre or were derived from Cre-expressing precursors. An array of brain tissue including the basal forebrain, hippocampus, olfactory bulb, and the granule cell layer of the lateral cerebellum, as well as the retinal pigmented epithelium and glia of the optic nerve originate from Cre-expressing neuroepithelial cells.

Animals↗

PubMed1982

Tissue specificity and clustering of methylated cystosines in bovine satellite I DNA.

The positions of all 5-methylcytosine (mC) residues in bovine satellite I DNA were determined by sequence analysis of native purified satellite I DNAs from three bovine tissues as well as from cloned DNA. The EcoRI cleavage units from thymus and liver were found to contain 1,402 residues; that from brain contained 1,401 residues. Satellite I DNA from thymus contained a total of 5.0% mC, whereas that from liver and brain contained 4.4% and 2.6% mC, respectively. Thus, the extent of methylation of this DNA is tissue-specific. So is the location. In each tissue, the location of mCs is nonrandom, consisting of three clusters of heavily methylated regions, each of about 200 bases. However, the extent of methylation within each cluster is tissue-specific. The mCs are located entirely in C-G doublets and primarily in palindromic sequences, C-C-G-G sequences (10 methylatable sites) are almost completely methylated in all tissues examined, but T-G-G-A sequences (16 methylated in all tissues examined, but T-G-G-A sequences (16 metylatable sites) are methylated to different extents in each tissue. Neither the tissue specificity of methylation nor the clustering pattern is detectable by examining only G-C-G-G sites, leading us to emphasize the importance of total sequence determination for genomic DNAs in studies of methylation. The clustering pattern, which is preserved despite a 2-fold difference in mC content between brain and thymus, may indicate a role for DNA methylation in chromatin structure.

5-Methylcytosine↗

PubMed1975

Tissue-specific DNA-protein complexes during azo dye hepatocarcinogenesis.

The immunological tissue specificity could be transferred from one chromatin preparation to another by reconstituting this protein fraction to the DNA and the remaining chromatin components."The immunological tissue specificity could be transferred from one chromatin preparation to another by reconstituting this protein fraction this protein fraction to the DNA and the remaining chromatin components.

Alpha-Globulins↗

PubMed1997

Neurabin: a novel neural tissue-specific actin filament-binding protein involved in neurite formation.

We purified from rat brain a novel actin filament (F-actin)-binding protein of approximately 180 kD (p180), which was specifically expressed in neural tissue. We named p180 neurabin (neural tissue-specific F-actin- binding protein). We moreover cloned the cDNA of neurabin from a rat brain cDNA library and characterized native and recombinant proteins. Neurabin was a protein of 1,095 amino acids with a calculated molecular mass of 122,729. Neurabin had one F-actin-binding domain at the NH2-terminal region, one PSD-95, DlgA, ZO-1-like domain at the middle region, a domain known to interact with transmembrane proteins, and domains predicted to form coiled-coil structures at the COOH-terminal region. Neurabin bound along the sides of F-actin and showed F-actin-cross-linking activity. Immunofluorescence microscopic analysis revealed that neurabin was highly concentrated in the synapse of the developed neurons. Neurabin was also concentrated in the lamellipodia of the growth cone during the development of neurons. Moreover, a study on suppression of endogenous neurabin in primary cultured rat hippocampal neurons by treatment with an antisense oligonucleotide showed that neurabin was involved in the neurite formation. Neurabin is a candidate for key molecules in the synapse formation and function.

Actins↗

PubMed1996

Tumor suppressor p53 down-regulates tissue-specific expression of tyrosinase gene in human melanoma cell lines.

Tyrosinase, the key gene in melanin pigment synthesis, is tissue-specifically expressed in melanocytic cells. Expression of this gene is regulated by various hormones, carcinogens, and environmental factors. The molecular basis underlying tyrosinase gene regulation is still not clear. In this report, we present the effects of tumor suppressor p53 protein in tyrosinase gene expression and melanin synthesis in human melanoma. After stable transfection of wild type p53 expression plasmid into a highly pigmented melanoma cell line, overexpression of wt p53 suppressed the pigmentation of the melanoma cells. The loss of pigmentation was associated with the loss of endogenous tyrosinase expression at the activity and mRNA levels. In order to determine whether the p53 repression of tyrosinase mRNA involved modulation of tyrosinase promoter activity, transient transfection approaches involving p53 expression plasmid and construct containing chloramphenicol acetyl transferase (CAT) reporter gene linked to 270 bp tissue-specific tyrosinase promoter have been used. p53 specifically repressed CAT gene expression from the tyrosinase promoter and not from the Rous sarcoma virus promoter. These data suggest that in human melanoma p53 down-regulates the tissue-specific expression of tyrosinase gene and subsequent melanin synthesis.

Chloramphenicol O-Acetyltransferase↗

PubMed2002

Lef-1 and Tcf-3 transcription factors mediate tissue-specific Wnt signaling during Xenopus development.

Wnt signaling functions repeatedly during embryonic development to induce different but specific responses. What molecular mechanisms ensure that Wnt signaling triggers the correct tissue-specific response in different tissues? Early Xenopus development is an ideal model for addressing this fundamental question, since there is a dramatic change in the response to Wnt signaling at the onset of zygotic gene transcription: Wnt signaling components encoded by maternal mRNA establish the dorsal embryonic axis; zygotically expressed Xwnt-8 causes almost the opposite, by promoting ventral and lateral and restricting dorsal mesodermal development. Although Wnt signaling can function through different signal transduction cascades, the same beta-catenin-dependent, canonical Wnt signal transduction pathway mediates Wnt signaling at both stages of Xenopus development. Here we show that, while the function of the transcription factor XTcf-3 is required for early Wnt signaling to establish the dorsal embryonic axis, closely related XLef-1 is required for Wnt signaling to pattern the mesoderm after the onset of zygotic transcription. Our results show for the first time that different transcription factors of the Lef/Tcf family function in different tissues to bring about tissue-specific responses downstream of canonical Wnt signaling.

Animals↗

PubMed1994

Tissue-specific expression of two alternatively spliced isoforms of the human insulin receptor protein.

Two insulin receptor mRNA species are expressed in human tissues as a result of alternative splicing of exon 11. This event is regulated in a tissue-specific manner. To date, there is little information about the relative abundance of the two receptor protein isoforms on the cell surface. The aim of the present investigation was to assess whether the tissue-specific expression of the two insulin receptor mRNA species is paralleled by a similar pattern of expression of the two receptor protein isoforms. To this end, we assessed the relative distribution of the two receptor variants in various human tissues at the mRNA and protein levels. A PCR-based technique was used to measure the relative abundance of the two mRNA species, and two immunological assays were used to measure the relative steady-state expression of the two receptor protein isoforms. The expression of the two insulin receptor protein isoforms followed the tissue-specific pattern of expression of the two mRNA species.

3T3 Cells↗

PubMed1992

Dipeptidase-C in Drosophila melanogaster: genetic, ontogenetic, and tissue-specific variation.

Dip-A, Dip-B, and Dip-C constitute structural genes for three peptidic enzymes in Drosophila melanogaster distinct from the leucine aminopeptidases. Their ontogenetic and tissue distributions of activities suggest the involvement of these enzymes in a general metabolic role, such as the regulation of amino acid and oligopeptide pools to make amino acids available for protein synthesis. Screening of chromosome substitution isogenic lines for DIP-C activity indicated that, like DIP-A and DIP-B, unlinked activity modifiers exist for Dip-C. The developmental profiles of dipeptidase activities are very similar, except in the pupal stage, during which DIP-C activity is markedly low compared to the other two enzymes. Intercorrelations of dipeptidase activities vary ontogenetically, which is consistent with the need for coordinate expression of these enzymes during certain developmental stages. Tissue-specific expression of dipeptidases in larvae and adults are also similar, although the relative levels of DIP-A activity differ from those of DIP-B and DIP-C in certain organs and body parts. Some of the differences among chromosome substitution lines for dipeptidase activities appear to be systemic, while others are developmental stage-specific and tissue-specific. Second- and third-chromosome variants for DIP-C activity differed in their tissue distribution. This is consistent with the presence of temporal and spatial variants in natural populations for other Drosophila enzymes.

Animals↗