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PubMedDate not supplied

Disease-specific and tissue-specific production of unintegrated feline leukaemia virus variant DNA in feline AIDS.

Feline leukaemia viruses (FeLVs) have long been known to be associated with induction of proliferative and anti-proliferative diseases of domestic cats. Strains of FeLV have been recognized which specifically induce lymphosarcoma, aplastic anaemia, myelodysplastic anaemia, and, recently, feline AIDS (acquired immune deficiency syndrome), a naturally occurring immunosuppressive syndrome strikingly similar to human AIDS which is lethal in 100% of inoculated and viraemic specific-pathogen-free (SPF) cats. Here, we have analysed FeLV DNA in tissues of 22 SPF cats that had been inoculated with the feline AIDS strain (FeLV-FAIDS) and we find two classes of viral DNA--a monotypic common form which is detectable in bone marrow regardless of disease state, and variant forms, recognizable by restriction site differences, whose appearance correlates with onset of disease symptoms and persists throughout the course of the disease. FeLV-FAIDS variant DNA is detected at high concentration (10-50 copies per cell) and principally as unintegrated viral DNA (UVD) in bone marrow of cats with feline AIDS. In marked contrast high levels of UVD were not present in cats in the terminal-stages of T-cell lymphosarcoma, aplastic anaemia, or myelodysplastic anaemia induced by other FeLV strains. These results parallel recent observations in humans, where high levels of UVD were sometimes found in cells derived from AIDS patients infected with human T-lymphotropic virus type III (HTLV-III)/lymph-adenopathy-associated virus (LAV), and suggest that persistence of unintegrated variant viral DNA is a crucial indicator of retrovirus-induced cytopathic disease syndromes such as AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Mouse pregnancy-specific glycoproteins: tissue-specific expression and evidence of association with maternal vasculature.

The pregnancy-specific glycoproteins (Psg) are secreted hormones encoded by multiple genes in rodents and primates, and are thought to act as immune modulators. The only Psg receptor identified is CD9, through which Psg17 induces cytokine production from macrophages cultured in vitro. We examined temporal and spatial aspects of Psg and CD9 expression during mouse pregnancy to determine whether their expression patterns support a role in immune modulation. Using in situ hybridisation, immunohistochemistry and RT-PCR we found Psg expression in trophoblast giant cells and in the spongiotrophoblast. Psg22 is the predominant Psg family member expressed in giant cells. Detectable Psg is associated predominantly with endothelial cells lining vascular channels in the decidua, rather than with maternal immune cell markers. CD9 expression exhibited partial overlap with Psg, but without exclusive co-localisation. CD9 was observed in decidual cells surrounding early implantation sites, and in the endometrium. However, embryo transfer of wild-type embryos to CD9-deficient females indicates that maternal CD9 is not essential for successful pregnancy.

Animals↗

PubMed2003

Identification of tissue-specific genes in nasopharyngeal epithelial tissue and differentially expressed genes in nasopharyngeal carcinoma by suppression subtractive hybridization and cDNA microarray.

Suppression subtractive hybridization (SSH) was performed for isolation of tissue-specific genes in nasopharyngeal epithelial tissue, by use of cDNAs from human adult nasopharyngeal epithelial tissue as tester and mixed cDNAs from esophagus, lung, liver, heart, stomach, spleen, skeletal muscle, kidney, and skin as drivers. Fourteen differentially expressed genes in nasopharyngeal epithelial tissue were obtained. Among these genes, LPLUNC1 and SPLUNC1 were confirmed to be specifically expressed in nasopharyngeal epithelial tissue and the trachea. A novel transcript of SPLUNC1, which we designate NASG, was found. We also combined SSH and cDNA microarray hybridization to identify genes whose expressions were altered in nasopharyngeal carcinoma (NPC). We used NPC cell line HNE1 and primary human embryo nasopharyngeal epithelial cells in one SSH experiment, and NPC biopsies and normal adult nasopharyngeal epithelial tissue in another. Some 1,200 SSH inserts from four subtractive cDNA libraries were arrayed onto nylon membranes by use of robotic printing. Differential gene expression was verified by hybridizing of the membranes with radioactively labeled first-strand cDNA from NPC cell line HNE1, primary human embryo nasopharyngeal epithelial cells, NPC biopsies, and normal adult nasopharyngeal epithelial tissue. Seventeen differentially expressed genes in NPC were obtained. Among these genes, we identified SPLUNC1 and LPLUNC1 to be down-expressed in NPC biopsies (34/48, 33/48).

Adult↗

PubMed1999

Development of a transgenic mouse model using rat insulin promoter to drive the expression of CRE recombinase in a tissue-specific manner.

BACKGROUND: Tissue-specific ablation of a gene using the Cre-loxP system has been used as an important tool to define its role, in addition to the total ablation, to avoid the embryonic lethality in case of wide expression of the target gene. METHODS: The RIP-Cre genetic construct was generated by standard subcloning techniques and microinjected into one cell embryo to develop the transgenic mouse line. Transgenic mice were screened by polymerase chain reaction (PCR) using DNA isolated from tell digestion. Tissue specificity of RIP was demonstrated by transient transfection of RIP-1acZ construct to NIT-1 cells (mouse insulinoma cell line) in vitro. RESULTS: The 448 nucleotides of RIP were sufficient for beta-cell specific expression of the reporter gene as evidenced by the presence of blue color in the nucleus of NIT-1 cells. Isolated RIP-Cre transgene was microinjected, and PCR screening identified two independent lines of transgenic mice. Tissue specificity of RIP was demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR) using the islet RNA from the transgenic mice. CONCLUSION: We have established a tissue-specific transgenic mouse model using Cre recombinase linked to rat insulin promoter (RIP) to drive the expression of the reporter gene specifically in the beta-cells. The RIP-Cre transgenic mice will allow beta-cell specific ablation of target gene(s) to define its role in the regulation of islet physiology.

Animals↗

PubMed2006

Computational analysis of tissue-specific combinatorial gene regulation: predicting interaction between transcription factors in human tissues.

Tissue-specific gene expression is generally regulated by more than a single transcription factor (TF). Multiple TFs work in concert to achieve tissue specificity. In order to explore these complex TF interaction networks, we performed a large-scale analysis of TF interactions for 30 human tissues. We first identified tissue-specific genes for 30 tissues based on gene expression databases. We then evaluated the relationships between TFs using the relative position and co-occurrence of their binding sites in the promoters of tissue-specific genes. The predicted TF-TF interactions were validated by both known protein-protein interactions and co-expression of their target genes. We found that our predictions are enriched in known protein-protein interactions (>80 times that of random expectation). In addition, we found that the target genes show the highest co-expression in the tissue of interest. Our findings demonstrate that non-tissue specific TFs play a large role in regulation of tissue-specific genes. Furthermore, they show that individual TFs can contribute to tissue specificity in different tissues by interacting with distinct TF partners. Lastly, we identified several tissue-specific TF clusters that may play important roles in tissue-specific gene regulation.

Binding Sites↗

PubMed1995

Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases.

We have expressed in Escherichia coli functionally active proteins encoded by two human cDNAs that were isolated previously by using rat 3 alpha-hydroxysteroid dehydrogenase cDNA as the probe. The expressed proteins catalyzed the interconversion between 5 alpha-dihydrotestosterone and 5 alpha-androstane-3 alpha,17 beta-diol. Therefore, we name these two enzymes type I and type II 3 alpha-hydroxysteroid dehydrogenases. The type I enzyme has a high affinity for dihydrotestosterone, whereas the type II enzyme has a low affinity for the substrate. The tissue-specific distribution of these two enzymes was determined by reverse transcription polymerase chain reaction using gene-specific oligonucleotide primers. The mRNA transcript of the type I enzyme was found only in the liver, whereas that of the type II enzyme appeared in the brain, kidney, liver, lung, placenta, and testis. The structure and sequence of the genes encoding these two 3 alpha-hydroxysteroid dehydrogenases were determined by analysis of genomic clones that were isolated from a lambda EMBL3 SP6/T7 library. The genes coding for the type I and type II enzymes were found to span approximately 20 and 16 kilobase pairs, respectively, and to consist of 9 exons of the same sizes and boundaries. The exons range in size from 77 to 223 base pairs (bp), whereas the introns range in size from 375 bp to approximately 6 kilobase pairs. The type I gene contains a TATA box that is located 27 bp upstream of multiple transcription start sites. In contrast, the type II gene contains two tandem AP2 sequences juxtaposed to a single transcription start site.

3-Hydroxysteroid Dehydrogenases↗

PubMed1987

A tissue-specific protein in rat osteogenic tissues.

A tissue-specific protein fraction has been detected in rat osteogenic tissue. Dissociative extraction of adult rat bone matrix with 4 M guanidinium chloride solution was followed sequentially by gel chromatography and polyacrylamide gel electrophoresis. By the latter procedure a prominent protein component of molecular weight 19,000 was isolated from the low molecular weight fraction, and antibodies directed against this protein were raised in rabbits. The antibodies were mainly against antigenic sites on this protein, as shown by protein blotting techniques. By embedding rat tissues in hydrophilic plastic and by using immunohistochemical procedures the presence of this protein was demonstrated specifically in bone matrix in vivo, in osteogenic tissue developing in diffusion chamber culture, and in a malignant osteoblast cell line (UMR 106). Soft tissues (liver, kidney, spleen, gut, skin, thymus, eye) showed no reactivity with the antiserum and in vitro a further malignant osteoblast cell line (ROS 17/2.8) did not synthesize the 19,000 molecular weight protein. This protein appears to be expressed solely by osteogenic tissue and may be used as a biochemical criterion of osteogenic differentiation.

Animals↗

PubMedDate not supplied

Organ- and tissue-specific stem cells and carcinogenesis.

Tissue-specific cancers originate in organ- or tissue-specific cells with the potential to proliferate. Recent reports have shown that every adult tissue may have its own stem cells. Cancer cells and organ- and tissue-specific stem cells and other progenitor cells are strikingly similar: both types self-renew, proliferate indefinitely, migrate, differentiate and express telomerase. Telomerase is a ribonucleoprotein that adds on nucleotides to the telomeres of chromosomes and so protects them from degradation, recombination and fusion at double-stranded DNA breaks. Cancer cells differ from normal tissue-specific stem cells only in their uncontrolled growth and altered genotypes. Based on the many similarities between cancer cells and stem cells, I propose that cancers (both solid and hematopoietic) arise from tissue-specific stem cells. Some such stem cells are always present among the stem cells in the peripheral blood of cancer patients and some of their asymptomatic first-degree relatives. It may therefore be possible to diagnose cancer predisposition early by identifying these circulating stem cells by their genetic defects. I, therefore, suggest that drug development for cancer treatment be directed towards tissue-specific stem cells.

Animals↗

PubMed2001

Regulation, function, and tissue-specific expression of cytochrome P450 CYP1B1.

Cytochrome P450 CYP1B1 is a relatively recently identified member of the CYP1 gene family. The purpose of this commentary is to review the regulatory mechanisms, metabolic specificity, and tissue-specific expression of this cytochrome P450 and to highlight its unique properties. The regulation of CYP1B1 involves a variety of both transcriptional and post-transcriptional mechanisms. CYP1B1 can metabolize a range of toxic and carcinogenic chemicals in vitro but in some cases with a unique stereoselectivity. Estradiol 4-hydroxylation appears to be a characteristic reaction catalyzed by human CYP1B1. However, there are considerable species differences regarding the regulation, metabolic specificity, and tissue-specific expression of this P450. In humans CYP1B1 is overexpressed in tumor cells, and this has important implications for tumor development and progression and the development of anticancer drugs specifically activated by CYP1B1.

Animals↗

PubMed1996

Prolonged infection in rhesus macaques with simian immunodeficiency virus (SIVmac239) results in animal-specific and rarely tissue-specific selection of nef variants.

We analyzed the sequence of nef genes from different tissues of three rhesus macaques that had been infected with molecularly cloned SIVmac239 for 88 to 92 weeks. Comparison of the predicted amino acid sequences revealed that each macaque had selected out specific amino acid substitutions and that most of this variation (70%) was confined to four regions, amino acids 39 to 75, 90 to 105, 153 to 167, and 191 to 217, comprising 36% of the protein. The nef genes in these animals underwent extensive genetic variation with average nucleotide and amino acid substitution rates varying from 0.86 to 2.84% and 2.47 to 6.27%, respectively, although tissue-specific selection of nef variants occurred in only 1 of 14 tissues examined in this study. Comparison of the rate of nucleotide and amino acid substitutions in the nef genes to those previously reported in the env in the central nervous system (CNS) and lymph node (LN) revealed that the predicted amino acid substitution rates for Nef were much higher than for the gp120 region of env in the CNS and LN tissues for one macaque. In the two other macaques, the predicted amino acid substitution rates were similar between these two proteins in LN tissues, but the amino acid substitution rates in Nef were significantly higher than in the gp120 from the CNS. Comparison of the nucleotide substitutions in the region of overlap between the env and the nef revealed that approximately 83% of the nucleotide substitutions in this area resulted in a Nef amino acid sequence change, 26% of the nucleotide substitutions resulted in a gp41 amino acid change, and 9.5% of nucleotide substitutions resulted in amino acid sequence changes in both proteins, suggesting a preference for the selection of amino acid substitutions in the Nef in these animals. Our results indicate that in animals infected with SIVmac239 for prolonged periods, variation in the nef occurs at rates similar to or exceeding that observed for the env gene.

Amino Acid Sequence↗

PubMed2002

[Tissue-specific action of peptides in tissue culture of rats of various ages].

There was studied the effect of polypeptide preparations isolated from the cerebral cortex (Cortexin), epiphysis (Epithalamin), liver (Hepalin), thymus (Thymalin) and small synthetic peptides--Cortagen, Epitalon, Livagen, Vilon on the development of explants from the cerebral cortex, brain subcortical structures, liver and thymus of rats of various age. With respect to the applied concentrations of the investigated peptides, they exerted tissue-specific effects in the organ-typical culture of animal tissues.

Aging↗

PubMed1997

Tissue-specific expression and promoter analyses of the human tissue kallikrein gene in transgenic mice.

The expression of the tissue kallikrein gene is tissue-specific and exhibits a complex pattern of transcriptional and post-translational regulation. Information concerning the mechanism of its tissue-specific expression has been limited owing to the lack of suitable cell lines for the expression study. We approached this problem by introducing human tissue kallikrein gene constructs into mouse embryos, creating transgenic lines carrying its coding sequence with varying lengths of the promoter region. One construct (PHK) contained 801 bp in the 5'-flanking region and two deletion constructs contained either 302 bp (D300) or 202 bp (D200) of the promoter region. The expression of human tissue kallikrein in these transgenic mice was monitored by Northern blot, reverse transcriptase-PCR followed by Southern blot, and radioimmunoassay. In all three lines, human tissue kallikrein was expressed predominantly in the pancreas and at lower levels in other tissues, including salivary gland, kidney and spleen. This pattern was similar to that of tissue kallikrein expression in human tissues. The D300 line has higher levels of transgene expression than the D200 and PHK lines. The results indicate that the 202 bp segment immediately upstream of the translation starting site is sufficient to direct a tissue-specific expression pattern of the human tissue kallikrein gene, and that regulatory elements might exist between -801 and -202.

Animals↗

PubMed1989

The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues.

The gene responsible for multidrug resistance (mdr), which encodes the P-glycoprotein, is a member of a multigene family. We have identified distinct mdr gene transcripts encoded by three separate mdr genes in the mouse. Expression levels of each mdr gene are dramatically different in various mouse tissues. Specific mdr RNA transcripts of approximately 4.5, 5, and 6 kilobases have been detected. Each of the mdr genes has a specific RNA transcript pattern. These results should be considered in relation to understanding the normal physiological function of the mdr multigene family.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

Control of NKT cell differentiation by tissue-specific microenvironments.

CD1d-restricted Valpha14 NKT cells play an important role in both Th1- and Th2-type immune responses. To determine whether NKT cells develop two functionally distinct subsets that provoke different types of responses, we examined the phenotypes and cellular functions of NK1.1(+) and DX5(+) T cells. We found that both NK1.1(+) and DX5(+) T cells are CD1d-restricted Valpha14 T cells with identical Ag specificities, phenotypes, tissue locations, and functions. Similar to the NK1.1 marker, the DX5 marker (CD49b) is expressed on mature NKT cells in both NK1.1 allele-positive and allele-negative strains. However, when NK1.1(+) and DX5(+) NKT cells isolated from different tissues were compared, we found that thymic and splenic NKT cells differed not only in their cytokine profiles, but also in their phenotype and requirements for costimulatory signals. Thymic NKT cells displayed the phenotype of activated T cells and could be fully activated by TCR ligation. In contrast, splenic NKT cells displayed the phenotype of memory T cells and required a costimulatory signal for activation. Furthermore, the function and phenotype of thymic and splenic NKT cells were modulated by APCs from various tissues that expressed different levels of costimulatory molecules. Modulation of NKT cell function and differentiation may be mediated by synergic effects of costimulatory molecules on the surface of APCs. The results of the present study suggest that the costimulatory signals of tissue-specific APCs are key factors for NKT cell differentiation, and these signals cannot be replaced by anti-CD28 or anti-CD40 ligand Abs.

Animals↗

PubMed2001

Tissue specificity of lymphocyte migration into sheep gingival tissue.

T cells show a bias in their migration pathways: some migrate preferentially to peripheral lymph nodes, some to mucosal tissues and some to peripheral tissues such as skin. The aim here was to determine the types of T cells that migrate preferentially into inflamed gingival tissue and compare this migration to that found in inflamed subcutaneous and mucosal tissues. The experiments were designed so that the simultaneous 3 h localization of two, differentially radiolabelled, lymphocyte populations (subcutaneously and mucosally derived) into sites of purified protein derivative/bacillus Calmette-Guerin-induced, delayed-type hypersensitivity, inflammatory lesions in skin, bowel and gingiva in the sheep model could be compared. The relative migration of two populations in each of the tissues was expressed as a ratio of the radioactivity of intestinal/subcutaneous lymphocytes recovered from that tissue. From nine experiments, the ratios [mean+/-S.E.M. (n)] for skin, bowel and gingiva were 0.53+/-0.02 (84), 1.98+/-0.11 (85), and 0.73+/-0.05 (29), respectively. These findings suggest that inflammation in skin and gingiva favoured the localization of subcutaneously derived lymphocytes (ratio significantly <1, P<0.025), while in bowel, the localization of intestinally derived lymphocytes was favoured (ratio significantly >1, P<0.025). Statistical analysis demonstrated that the relative localization of the two lymphocyte populations to the gingival lesions differed significantly from that for inflamed skin and bowel lesions (P<0.05). When tumour necrosis factor-alpha was used as a non-antigenic inflammatory agent to induce lymphocyte migration into skin and gingiva, a similarly greater increase in the localization of subcutaneously derived lymphocytes was detected, but the relative localization of lymphocytes was not significantly different between the two tissues. Therefore, it appears that there is tissue specificity in the migration of lymphocytes into the inflamed gingival tissues and that antigen is required for distinct tissue-specific lymphocyte traffic to occur.

Analysis of Variance↗

PubMed1985

Aryl hydrocarbon hydroxylase tissue-specific activities: evidence for baseline levels in mammalian tissues.

The tissue-specific activities (units per gram tissue) of arylhydrocarbon hydroxylase benzo[a]pyrene [AHH(BaP)] (EC 1.14.14.2) in human, mouse, rat, and hamster have been reviewed. Three categories of AHH activities are defined: baseline values from tissues that have been protected from adventitious exposures to AHH inducers; background levels from tissues where there have been no overt measures to protect against exposure; and induced levels resulting from overt exposure to chemical inducers. Evidence that the baseline category exists is derived from the observations that an upper limit of AHH tissue-specific activity of about 1.5 nmol/h . g tissue occurs in human placenta, human foreskin, lymphocyte, and epitheliod and fibroblastoid cell lines; mouse lung and liver; rat fetal liver, and noninducible rat cell lines from lung, liver, embryo kidney, and adrenals; and hamster kidney. The collected values for nonexposed tissues range from 0.02 nmol/h . g to values less than 1.5 nmol/h . g. The most consistent observation of this type was from human placental material from nonsmoking mothers. Animals raised under standard laboratory conditions without special dietary precautions show background AHH activities that range from 2 nmol/h . g to 200 nmol/h . g in portal of entry tissues such as liver, lung, and intestines. Almost all tissue samples showed induced AHH levels of up to 500 nmol/h . g when those tissues were overtly exposed to substances containing chemical inducers of AHH. Measurements of placental AHH from smoking mothers showed that more than 95% of those samples had AHH values exceeding 2.5 nmol/h . g. This natural bimodal distribution of AHH activities, across species and in different tissues, of baseline values of less than 1.5 nmol/h . g and background or induced AHH activities with values greater than 1.5 nmol/h . g, may provide a reference set of values for use in quantification of the role of AHH in the induction of disease.

Animals↗

PubMed2000

Effects of chronic sublethal exposure to waterborne Cu, Cd or Zn in rainbow trout 2: tissue specific metal accumulation.

Tissue specific metal accumulations (gills, liver, kidney and whole body) in rainbow trout (Oncorhynchus mykiss) were compared during chronic exposure (up to 100 days) to sublethal levels of waterborne Cd (3 µg.l(-1)), Cu (75 µg.l(-1)) or Zn (250 µg.l(-1)) in moderately hard water (hardness of 140 mg.l(-1), pH 8.0). A general pattern of tissue metal increase and stabilization was evident for all three metals, although the degree and time course of accumulation varied. The exception to this general pattern was a lack of Zn accumulation in the liver and kidney although small amounts did accumulate in the gills and whole body. Accumulation of Cu occurred primarily in the liver while for Cd the kidney was the major organ of accumulation. Exponential modeling was employed to compare and contrast the saturation concentration and time to half saturation of various tissues. Accumulation of essential metals (Cu and Zn), if it occurred, was rapid and increases were relatively low. For example the time to half saturation during Cu exposures was always less than 2 weeks and the maximum level of accumulation was less than four times background levels. For non-essential Cd, time to half saturation for the liver and kidney was always longer than 5 weeks and modeled saturation concentrations were up to 80-fold higher than background. The response to Cu and Zn suggested an active regulation of tissue burdens while that of Cd appears to be more passive, resulting in continuous metal accumulation over an extended time course. While the initial patterns of accumulation for each metal were generally consistent with the damage, repair and acclimation pattern from concurrent physiological measurements it was clear that tissue metal accumulation was not a good indicator of either exposure of physiological impact.

Journal Article↗

PubMed1992

Tissue-specific nutritional regulation of angiotensinogen in adipose tissue.

Recent studies have found that angiotensinogen is expressed in white and brown fat pads, and adipocytes have been implicated as a primary source of angiotensinogen in several other tissues. The functional significance of this unexpected expression is unknown. To address this, we studied angiotensinogen messenger RNA (mRNA) expression and angiotensinogen secretion in adipose tissue and isolated adipocytes comparing fasted and refed rodents and those with genetic obesity with normal controls. Control 2-month-old Sprague-Dawley rats, those fasted for 3 days, or those fasted for 2 days and refed for 6 days were killed, and adipocytes were isolated from epididymal fat pads using collagenase digestion. Angiotensinogen mRNA was reduced to 14.6 +/- 2.3% of control levels under fasted conditions and increased to 228 +/- 53% of control levels after refeeding. Angiotensinogen release from adipocytes was reduced to 33% of control levels by fasting and increased to 183% by refeeding. These effects of fasting and refeeding on angiotensinogen regulation were tissue specific since liver angiotensinogen mRNA and serum angiotensinogen concentrations were unaffected. Systolic blood pressure, however, was modulated by fasting and refeeding in a manner parallel to adipocyte angiotensinogen expression. In related experiments, angiotensinogen secretion per epididymal fat pad of the ob/ob mouse model of obesity was increased an average of 3.4-fold compared with control. We conclude angiotensinogen expression in white adipocytes is regulated nutritionally in a tissue-specific manner. We propose that adipocyte angiotensinogen could play a previously unrecognized role in regulating adipose tissue blood supply and thereby fatty acid efflux from fat.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗