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At least 73 records · Page 4Linked to original sources
PubMed1994

Tissue-differential expression of two distinct genes for human IMP dehydrogenase (E.C.1.1.1.205).

Human IMP dehydrogenase (E.C. 1.1.1.205) is recently regarded as a potent targeting enzyme for immunosuppressive drugs. Tissue differential expressions of human type I and type II IMP dehydrogenase were investigated in sixteen human adult organs (heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocytes) and five human fetal organs (heart, brain, lung, liver, kidney) using Northern blot analysis. In all tissues examined in this study, the sizes of mRNAs of each isoform were identical, respectively. The 2.3 kb type II mRNA was shown predominantly, and the 3.5 kb type I mRNA level was lower than type II in most human tissues examined. In contrast, type I IMPDH gene expressed higher than type II in peripheral blood leukocytes, uniquely. We also demonstrated that both type I and type II IMPDH genes are widely distributed among various species by Southern blot analysis. Interestingly, type I IMPDH gene may have multiple gene families in primates.

Adult↗
PubMed1997

A biomechanical regulatory model for periprosthetic fibrous-tissue differentiation.

Loosening of implants in bone is commonly associated with a development of fibrous interface tissues, due to interface gaps and a lack of mechanical stability. It has been postulated that the differentiation of these tissues to fibrocartilage or bone is governed by mechanical stimuli. The objective of our research is to unravel these relationships to the extent that the question whether an implant will loosen can be answered from initial conditions determined by implant and interface morphology, and functional loads. In this project we studied the hypothesis that distortional strain and interstitial fluid flow are the mechanical stimuli governing tissue differentiation. For that purpose, a biomechanical regulatory model was developed and used in association with a finite element code to simulate animal experiments with implants moving in bone. The similarities between the implant incorporation process found in the experiment and its simulation with the computer model demonstrate that our hypothesis is viable from a regulatory point of view.

Journal Article↗
PubMed1997

Ontogenesis of prolactin receptors in the human fetus in early gestation. Implications for tissue differentiation and development.

To explore potential roles for lactogenic hormones in human fetal development, we examined the distribution and ontogenesis of expression of prolactin receptors (PRLRs) in human fetal tissues at 7.5-14 wk of gestation and in tissues of the embryonic and fetal rat on days e12.5-e20.5. Histochemical analysis of PRLR immunoreactivity in the human fetus and fetal rat revealed novel and unexpected patterns of receptor expression. Most remarkable was the appearance in early fetal development of intense PRLR immunoreactivity in tissues derived from embryonic mesoderm, including the periadrenal and perinephric mesenchyme, the pulmonary and duodenal mesenchyme, the cardiac and skeletal myocytes, and the mesenchymal precartilage and maturing chondrocytes of the endochondral craniofacial and long bones, vertebrae and ribs. Striking changes in the cellular distribution and magnitude of expression of PRLRs were noted in many tissues during development. In the fetal adrenal the initial mesenchymal PRLR expression is succeeded by the emergence of PRLR immunoreactivity in deeper fetal cortical cell layers. In the fetal kidney and lung, the invagination of cortical mesenchyme is accompanied by progressive PRLR immunoreactivity in bronchial and renal tubular epithelial cells. In the pancreas, the PRLR is expressed primarily in acinar cells and ducts in early gestation; in late gestation and in the postnatal period, the PRLR is expressed predominantly in pancreatic islets, co-localizing with insulin and glucagon. Finally in fetal hepatocytes, PRLR immunoreactivity increases significantly between embryonic days e52 and e96 in the human fetus and between days e16.5 and e18.5 in the fetal rat. In addition to playing important roles in reproduction, lactation, and immune function, the lactogenic hormones likely play roles in tissue differentiation and organ development early in gestation.

Adrenal Glands↗
PubMed2000

Expression patterns of the multiple transcripts from the folylpolyglutamate synthetase gene in human leukemias and normal differentiated tissues.

Folylpoly-gamma-glutamate synthetase (FPGS) catalyzes the activation of folate antimetabolites in mammalian tissues and tumors. We have determined the sequence, abundance, and function of human FPGS transcripts and found some striking differences to transcription of the mouse gene that allow production of FPGS isoforms in mouse liver and dividing tissues. Multiple human transcripts were identified, including the homolog of the mouse transcripts that initiate at two upstream exons. However, the human FPGS upstream promoter is infrequently used, and transcripts from this promoter include sequences homologous with only one of the upstream exons found in the mouse. The downstream promoter generates an array of transcripts, some of which do not produce active enzyme, a phenomenon not seen in the mouse. Hence, the dual promoter mechanism directing expression of FPGS isozymes in mouse tissues is not conserved in humans, and, unlike the mouse downstream promoter, the human downstream promoter is active in both dividing and differentiated tissues. This study raises questions about the differences in function served by the two mouse FPGS isozymes and how, or if, human tissues fulfill these functions. How humans and mice produce FPGS in only a subset of tissues using such different promoter structures also becomes a central issue.

Alternative Splicing↗
PubMed1988

The pigmented epithelium sustains cell growth and tissue differentiation of chicken retinal explants in vitro.

Embryonic retinae from 5-6-day-old chicks (E5-E6) were cut into stripes either in close contact with (RPE stripes) or in absence of the neighboring retinal pigmented epithelium (R stripes). The stripes were explanted and cultivated in vitro for up to 6 days, during which time they show the following differences in their characteristics of growth and differentiation. Compared with R stripes, RPE stripes morphologically showed a significant increase in size during the first 2 days in culture. Using E5 tissue, this is also demonstrated by a higher rate of cell proliferation (as measured by uptake of radioactive thymidine as well as by DNA contents). In contrast, R stripes after two days in culture show a much stronger neurite growth. After longer periods of culturing (5-6 days) we can show by cholinesterase histochemistry (AChE and BChE) and by PNA-lectin binding that the RPE stripes have started to form all major layers of the in vivo retina, whereas R stripes remain unstratified and start to degenerate earlier. We conclude that the pigment epithelium might exert a specific stimulus on growth and tissue differentiation of the neural retina not only during in vitro, but possibly also during in vivo development. The in vitro methods introduced here could become useful model systems to further investigate the significance of the RPE for developmental, regenerative and even adult processes of the neural retina. Their future applicability in ophthalmologic research is briefly discussed.

Animals↗
PubMed2005

Cathepsin D expression in human colorectal cancer: relationship with tumour type and tissue differentiation grade.

OBJECTIVE: Cathepsin D (CD) is one of the main proteolytic enzymes contributing to the development of cancer. The aim of this study was to CD activity assay in the homogenates of tissues from the centre of the tumour (0) and tumour free area 2 cm, and 5 cm from the tumour border in human colorectal cancer. Activity in the centre of the tumour was compared with immunohistochemical expression CD. METHODS: CD activity was measured using acid denatured Hb as a substrate. For immunohistochemical staining peroxidase method was used. RESULTS: Activity of CD was significantly higher (15-fold) in tumour tissue homogenates in comparison to normal mucosa adjacent (control) (p < or = 0.0001) and raised parallel to the stage of tumour tissue differentiation grade. CD activity decreased significantly (p < or = 0.0001) with the distance from the tumour border 2 cm (12.7 fold) and 5 cm (5.7 fold) in comparison to the centre of the tumour. In immunohistochemical examinations CD was detected as diffuse cytoplasmic as well as fine granular staining of the cytoplasm, with occasional coarse cytoplasmic granules staining in the same cases that were positive for both. Positive staining was observed in 2 of 3 in well-differentiated (66%), 4 of 10 in moderately-differentiated (40%) and 4 of 5 in poorly-differentiated (80%), tubular adencarcinomas represented: 3 of 7 (42%) and 9 of 13 in invasive adencarcinoma (69%). CONCLUSION: We have observed a wide range of cathepsin D and their antigen expressions patterns in colorectal tumours with the development the disease stage, this finding may be used as a daignostic tumor marker in colorectal cancer.

Adenocarcinoma↗
PubMed2000

Wear particle diffusion and tissue differentiation in TKA implant fibrous interfaces.

In the context of mechanical loosening, we studied the hypothesis that wear-particle migration in the fibrous membrane under tibial plateaus after total knee arthroplasty can be explained by the pumping effects of the interstitial fluid in the tissue. Further, as a secondary objective we investigated the possibility that interface-tissue differentiation is influenced by interstitial fluid flow and strain, as mechanical effects of interface motions. For comparative reasons, we analyzed a previously published simplified two-dimensional finite-element model, this time assuming biphasic tissue properties. We wanted to determine hydrostatic pressure and flow velocities in the fluid phase, in addition to stresses and strains, for time-dependent loading of the plateau. We found that fluid flow in the interface was extremely slow, except in the periphery. Hence, loosening due to particle-induced bone resorption appears improbable. The results, however, do support the idea that particles migrate with fluid flow, when such flow occurs. Where fibrous tissue tends to be prominent in reality, the fluid is repeatedly extruded and reabsorbed in the model. Where these values are low, fibrocartilage is commonly found. When material properties were varied to subsequently represent fibrocartilage and two stages of mineralization, the strains and fluid velocities is reduced. Fluid pressure, however, did not change. Our results refute the hypothesis that wear particles are pumped through the interface tissue below a TKA but support the hypothesis that interface tissue type and loosening processes are influenced by mechanical tissue variables such as tissue strain and interstitial fluid velocity.

Biomechanical Phenomena↗
PubMed1998

Rat G protein-coupled receptor kinase GRK4: identification, functional expression, and differential tissue distribution of two splice variants.

G protein-coupled receptor kinases (GRKs) specifically phosphorylate the agonist-occupied form of G protein-coupled receptors, leading to the homologous mode of desensitization. We report here on the cloning of complementary DNAs that encode two rat GRK4 variants. Rat GRK4A (575 amino acids) displays 76% identity with the long human GRK4 splice variant. Rat GRK4B (545 amino acids) delineates a new variant that is identical to GRK4A except for a 31-amino acid deletion in the N-terminal domain, corresponding to exon VI in the human GRK4 gene. GRKs4A and B are likely produced by alternative splicing from a single gene, the partial characterization of which revealed a structural organization similar to that of the human GRK4 gene. GRK4A messenger RNA (mRNA) is abundant only in testis. A combination of in situ hybridization and quantitative RT-PCR studies demonstrated that GRK4A mRNA level increases during testicular development and predominates in leptotene to late pachytene primary spermatocytes and round spermatids. GRK4B mRNA is poorly expressed in testis and most rat tissues but is heterogeneously distributed in the kidney, with 20-fold enrichment in the outer medulla. GRKs4A and B are both functional protein kinases, as demonstrated in a rhodopsin phosphorylation assay. The differential tissue distribution of GRKA4 and GRK4B suggests that individual GRK4 variants may serve distinct physiological functions.

Amino Acid Sequence↗
PubMed1978

[Sonographic representation of fibroses (a contribution to the problem of tissue differentiation) (author's transl)].

Twelve patients with radiogenic fibroses were submitted to a sonographic examination by means of a grey-scale compound-scanner. As these skin fibroses are well suited for inspection and palpation, they are qualified to serve as a model with regard to the problem of sonographic tissue differentiation. Fibroses of medium and high degree are determined by characteristic properties in the B picture, whereas fibroses of low degree cannot be recorded by this technique.

Adult↗
PubMed1994

The effects of micromotion and particulate materials on tissue differentiation. Bone chamber studies in rabbits.

Motion at the interface between bone and implants for joint replacement may interfere with osseointegration and prosthesis stabilization. Particulate materials may cause foreign body and chronic inflammatory reactions resulting in bone resorption (osteolysis). The micromotion chamber (MC) and the bone harvest chamber (BHC) were implanted in the rabbit tibia, and the effects of micromotion and phagocytosable particulate materials on tissue formation within the chamber were assessed by studying bone ingrowth into a 1-mm pore. Using the MC, one short daily episode of motion (20 cycles/day, 0.5 mm amplitude) for three weeks decreased the amount of bone ingrowth. Using a different pore configuration, the same parameters of motion increased bone ingrowth. Increasing the amplitude of motion (from 0.5 to 0.75 mm), or the number of daily motion periods (from one to two per day) then decreased bone ingrowth. These studies suggest the existence of a window of externally applied strain: a small stimulus may facilitate and a large stimulus may discourage bone formation within the chamber. Cessation of a given set of motion parameters (producing primarily fibrous tissue) for an additional three weeks was accompanied by tissue differentiation into bone. Using the BHC, small, phagocytosable particles of bone cement, high density polyethylene and cobalt chrome alloy, at a concentration of 1.0 x 10(8) particles/mL, caused a foreign body reaction and inhibited the ingrowth of bone. Particles of titanium alloy had no effect on net bone formation. In studies using normal and immunodeficient rats, T lymphocytes were not a prerequisite for macrophages to phagocytose polyethylene particles. In the clinical situation, micromotion and particulate debris may be synergistic in producing prosthetic loosening. If an implant does not undergo osseointegration due to excessive micromotion, the fibrous tissue interface may provide a conduit for the subsequent migration of particles around the implant.

Animals↗
PubMed1995

Tissue differentiation and correlated changes in enzymatic activities during primary antler development in fallow deer (Dama dama).

BACKGROUND: Deer antlers are useful models for studying bone growth and biomineralization in mammals. To achieve a better understanding of the mechanisms underlying the formation of primary cranial appendages in deer, the present study relates the histogenesis of primary antlers to changes in enzymatic (phosphatase) activities in the different tissue zones of this organ. METHODS: The growing tips of the primary antlers (4.3 to 5 cm in length) were removed from five fallow bucks, aged about 10 months. Part of the material was processed for light microscopy. The other part was cryofixed, and the different histologically defined regions were analyzed for the activities of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) as well as for the concentrations of inorganic and organic phosphate. RESULTS AND CONCLUSIONS: Histologically, the primary antler could in distoproximal direction be divided into eight different zones (dermis; perichondrium; zones of cartilage formation, hypertrophy, mineralization, and degeneration; primary spongiosa; secondary spongiosa). The histological results demonstrate that the elongation of the primary antler proceeded through a modified form of endochondral ossification, resembling that seen during formation of pedicles and secondary antlers. The concentrations of the extractable activities of ALP and TRAP progressively increased from the perichondrium to the zone of cartilage mineralization. Thus, highest activity of TRAP during primary antler formation occurred at an earlier stage of tissue differentiation than in somatic endochondral ossification, where the enzyme is a biochemical marker of osteoclastic activity during bone remodeling. The present results might reflect the presence of osteoclastic precursor cells in the zone of cartilage mineralization as an adaptation to the rapidity of antler growth. Our findings of the contents of extractable ALP, inorganic and organic phosphate in the different tissue zones of the developing primary antler are in good agreement with previous studies analyzing epiphyseal growth plates and point to the fact that ALP causes a rise in inorganic phosphate and the removal of inhibitors for mineralization, like pyrophosphate.

Acid Phosphatase↗
PubMed1999

Phenolic content in differentiated tissue cultures of untransformed and Agrobacterium-transformed roots of anise (Pimpinella anisum L.).

To investigate the role of differentiation of anise tissue cultures on total phenolic and anethole contents, benzylaminopurine- and thidiazuron-induced shoot cultures were generated from roots of the A-8 clonal line and its Agrobacterium rhizogenes-induced genetically transformed derivative JB-10. Embryogenic cultures were induced following 2,4-D treatment. Root cultures were multiplied on hormone-free medium. The effect of proline on differentiation and phenolic synthesis was also investigated. GC/MS studies indicate that anethole was not produced in root or other differentiated cultures. The predominant phenolic metabolite, however, was an anethole precursor, epoxypseudoisoeugenol-2-methylbutyrate (EPB). Total phenolics and EPB contents were highest in root cultures, which also correlated with higher proline content. Embryo and shoot cultures had reduced phenolic level and EPB and proline contents. Antioxidant activity in all differentiating cultures was high on day 60 compared to that on day 30, and there was no significant difference between differentiating tissues. This indicated that antioxidant protection might be linked not only to phenolics but to other nonphenolic metabolites as well.

Apiaceae↗
PubMed2000

The relationship between SMN, the spinal muscular atrophy protein, and nuclear coiled bodies in differentiated tissues and cultured cells.

The spinal muscular atrophy protein, SMN, is a cytoplasmic protein that is also found in distinct nuclear structures called "gems." Gems are closely associated with nuclear coiled bodies and both may have a direct role in snRNP maturation and pre-RNA splicing. There has been some controversy over whether gems and coiled bodies colocalize or form adjacent/independent structures in HeLa and other cultured cells. Using a new panel of antibodies against SMN and antibodies against coilin-p80, a systematic and quantitative study of adult differentiated tissues has shown that gems always colocalize with coiled bodies. In some tissues, a small proportion of coiled bodies (<10%) had no SMN, but independent or adjacent gems were not found. The most striking observation, however, was that many cell types appear to have neither gems nor coiled bodies (e.g., cardiac and smooth muscle, blood vessels, stomach, and spleen) and this expression pattern is conserved across human, rabbit, and pig species. This shows that assembly of distinct nuclear bodies is not essential for RNA splicing and supports the view that they may be storage sites for reserves of essential proteins and snRNPs. Overexpression of SMN in COS-7 cells produced supernumerary nuclear bodies, most of which also contained coilin-p80, confirming the close relationship between gems and coiled bodies. However, when SMN is reduced to very low levels in type I SMA fibroblasts, coiled bodies are still formed. Overall, the data suggest that gem/coiled body formation is not determined by high cytoplasmic SMN concentrations or high metabolic activity alone and that a differentiation-specific factor may control their formation.

Animals↗
PubMed2003

Identification and characterization of a new human type 9 cGMP-specific phosphodiesterase splice variant (PDE9A5). Differential tissue distribution and subcellular localization of PDE9A variants.

Previously, four splice variants of human cGMP-specific phosphodiesterase (PDE) 9A (PDEs 9A1, 9A2, 9A3 and 9A4) have been identified. In this study, we have cloned a cDNA representing a new human PDE9A variant (PDE9A5). PDE9A5 encodes a protein of 492 amino acids, smaller than PDEs 9A1 and 9A2 but larger than PDEs 9A3 and 9A4. The exon structure of PDE9A5 is different from those of PDEs 9A1, 9A2, 9A3 and 9A4 in that, of the 20 exons of PDE9A gene, it lacks exons 2 and 5. PDE9A5 has been characterized in comparison with PDE9A1, the longest PDE9A variant. PDEs 9A5 and 9A1 have similar enzymatic properties. They both have a high affinity for cGMP with similar Km values (0.39 and 0.25 microM, respectively), although they have slightly different Vmax values (2.55 and 0.96 micromol/min/mg, respectively). They exhibit very similar divalent metal ion dependency and inhibitor sensitivity. Real-time quantitative PCR analysis shows that PDEs 9A5 and 9A1 exhibit differential tissue distribution. They are highly expressed in immune tissues (spleen, lymph node and thymus) and are more abundant in T cells than in B cells, neutrophils and monocytes. When transiently expressed in HEK293 cells, PDEs 9A5 and 9A1 proteins exhibit differential subcellular localization. PDE9A5 localizes exclusively in the cytoplasm, whereas PDE9A1 localizes in the nucleus only. The nuclear localization of PDE9A1 is dependent on a unique pat7 motif. By Western blot analysis, native PDE9A1 is detectable in the nucleus but not in the cytoplasm of T cells. Thus, to our knowledge, PDE9A1 is the only PDE isoform found to localize exclusively in the nucleus. We speculate that the physiological role of the PDE9A diversity may be imparting cGMP-metabolizing ability to specific cellular compartments in appropriate tissues.

1-Methyl-3-isobutylxanthine↗
PubMed2001

[Features of tissue differentiation of the thyroid gland in residents of Magadan].

The histological structure and morphometric parameters of the thyroid gland were examined in fetuses, newborns and infants during the early postnatal period to assess the peculiarities of thyroid differentiation in Magadan goiter endemic region. It was demonstrated that fetal thyroid gland remained immature. Functional strain of thyroid structures was shown in neonatal period that is considered to be the manifestation of the adaptive responses of the newborn. In infants aged 2-3 months thyroid gland attained definitive morphometric parameters that indicated its functional maturity. Low rate of tissue differentiation in the thyroid gland during prenatal period may result from iodine deficiency in both mother and fetus, which is aggravated by the unfavorable natural climatic factors of the North.

Cell Differentiation↗
PubMed1984

Monoclonal antibodies to human sarcoma and connective tissue differentiation antigens.

The use of monoclonal antibodies to distinguish human sarcoma from carcinoma cells has been explored. Spleen cells from a BALB/c mouse immunized with a human malignant fibrohistiocytoma were fused with cells of the mouse P3U1 plasmacytoma cell line. Antibodies were then screened for reactivity against human sarcoma and carcinoma cells growing in culture. This work has yielded 2 immunoglobulin G monoclonal antibodies VIE4 and VIF3 which, respectively, reacted with 85% (17 of 20) and 90% (18 of 20) of sarcoma lines tested but with none of eight carcinoma cell line preparations. Reactivity against normal fibroblasts was also demonstrated. By immunofluorescence, the antigens detected by the two antibodies appear to have distinctive intracellular distributions. Immunoprecipitation with VIF3 has shown that it is detecting a protein with a molecular weight of 70,000. When tested against pathological frozen tissue sections, VIF3 reacted with four of 11 and VIE4 with three of 11 human sarcomas but with none of ten carcinomas tested. VIF3 occasionally bound to normal adult connective tissues, whereas no such reactivity was seen with VIE4. These antibodies appear to be directed to fibroblastic markers associated with sarcomas and connective tissue differentiation antigens.

Animals↗
PubMed2003

Breast tissue differentiation using arterial spin tagging.

An arterial spin tagging (AST) pulse sequence has been developed to measure T(1) and relative blood perfusion. This full sequence is composed of three sequences: selective tagging, nonselective tagging, and nontagging. Perfusion quantification error resulting from imperfect inversion and acquisition slice profiles has been addressed in the literature. In this work, the error is reduced through the application of optimized Shinnar-Le Roux (SLR) RF pulses and a semi-log linear regression data-processing technique. A threshold approach based on the breast tissue T(1) and relative blood perfusion is introduced to show that these two parameters can be applied to breast tissue differentiation and potentially to cancer detection.

Breast↗
PubMed1990

Analysis of cDNA for human erythrocyte ankyrin indicates a repeated structure with homology to tissue-differentiation and cell-cycle control proteins.

Analysis of complementary DNA for human erythroid ankyrin indicates that the mature protein contains 1,880 amino acids comprising an N-terminal domain binding integral membrane proteins and tubulin, a central domain binding spectrin and vimentin, and an acidic C-terminal 'regulatory' domain containing an alternatively spliced sequence missing from ankyrin variant 2.2. The N-terminal domain is almost entirely composed of 22 tandem 33-amino-acid repeats. Similar repeats are found in yeast and invertebrate proteins involved in cell-cycle control and tissue differentiation.

Amino Acid Sequence↗