[Soft tissue diagnosis on the extremities using soft tissue radiography. Part II. Diseases of the Achilles tendon and the surrounding tissues (author's transl)].
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Achilles Tendon↗
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Different rates of ageing process in epididymal fatty tissue, aorta and myocardium in rats index: the tissue triglyceride-lipolytic activity in relation to the triglyceride content of these tissues.
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Adipose Tissue↗
The influence of dead and fixed dead tissue in the living organism. II. The tissue reaction to implantation of autologous dead tissue.
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Animals↗
A comparative study of cytokine gene transcripts in normal and malignant breast tissue and primary cell cultures derived from the same tissue samples.
Using a differential centrifugation method followed by culture in selective medium, we have successfully isolated and maintained individual epithelial and stromal cells from normal (n = 10) and malignant (n = 6) human breast tissue and characterised their phenotype by immunocytochemistry. Further, we have studied expression of the cytokine genes IL-1beta, IL-6, IL-8 and TNF-beta in each cell fraction by RT-PCR and have compared these results with cytokine gene expression in tissue extracts from which primary cultures were derived. In breast tumours, there was near complete absence of IL-1beta in both whole tissue and cell fractions, and in normals it was present in only 3/10 tissue preparations, with increased expression in stromal (6/10) and epithelial (5/10) cell samples. IL-6 was constitutively expressed in all tumour-derived breast tissue samples but down-regulated in tumour cell cultures, with the opposite result in normal breast. Near identical levels of IL-8 expression were found throughout each preparation, irrespective of tissue origin. TNF-beta was expressed in all normal tissue samples, in 9/10 epithelial preparations but in only 6/10 stromal preparations. In tumours, TNF-beta was associated predominantly with whole tissue or stromal samples, with reduced expression in epithelial preparations. Our data confirm that primary cultures of normal and malignant human breast tissue can be successfully separated into epithelial and mesenchymal cell populations and their phenotype can be maintained in culture for up to 30 days. However, this cellular separation does alter the cytokine profiles; therefore, experimental findings with isolated cells should be treated with a caveat.
Base Sequence↗
Dendritic cells govern induction and reprogramming of polarized tissue-selective homing receptor patterns of T cells: important roles for soluble factors and tissue microenvironments.
Tissue-selective homing is established during naive T cell activation by the tissue microenvironment and tissue-specific dendritic cells (DC). The factors driving induction and maintenance of T cell homing patterns are still largely unknown. Here we show that soluble factors produced during the interaction of T cells with CD11c(+) DC isolated from skin- or small intestine-associated tissues differentially modulate expression of the corresponding tissue-selective homing receptors (E-selectin ligands and alpha4beta7 integrin/CCR9, respectively) on murine CD8(+) T cells. Injection of tissue-specific DC via different routes induces T cells with homing receptors characteristic of the corresponding local tissue microenvironment, independent of the origin of the DC. These data indicate an important role for signals delivered in trans. Moreover, DC can reprogram the homing receptor expression on T cells previously polarized in vitro for homing to skin or small intestine. Importantly, skin-homing memory T cells stimulated directly ex vivo can also be reprogrammed by intestinal DC to a gut-homing phenotype. Our results show that tissue-selective homing receptor expression on effector and memory T cells is governed by inductive as well as suppressive signals from both DC and tissue microenvironments.
Animals↗
[Tissue engineering of vascularized bone and soft tissue transplants].
The utilization of in vitro angiogenesis in tissue engineering might be useful in order to establish an artificial vascular network. However, it remains unclear how far the in vitro preformation of vascular structures may contribute to the perfusion of larger artificial tissue aggregates regarding the improvement of oxygenation and nutrition. In an in vitro study, we developed a model of a vascularized tissue. Stromal cells of a target tissue, e.g., adipose tissue or bone tissue, were expanded in vitro and seeded onto microcarriers or microparticles. Densely covered microcarriers were brought into a fibrin matrix together with endothelial cells. In order to demonstrate the formation and stabilization of capillary-like structures, UEA-I labeled specimens were evaluated using laser scanning microscopy and digital image analysis. The stabilization of capillary-like structures was better with stromal cells from bone marrow than from adipose tissue. In one of the culture aggregates, the total length of capillary-like structures increased after 6 weeks of cultivation to up to 140 mm/mm3. Additional tests were performed utilizing hyperbaric oxygenation. In the oxygenation group, a significant increase in the length of capillary-like structures was found. The method implies the option of coculturing different tissue elements and of an in vitro preformation of vascularized tissues.
Bone Transplantation↗
Soft tissue removal by maceration and feeding of Dermestes sp.: impact on morphological and biomolecular analyses of dental tissues in forensic medicine.
Maceration techniques remove soft tissue by the destruction of biomolecules, but the applied techniques may also affect the morphology and the molecular integrity of the hard tissue itself. The impact of seven different techniques for soft tissue removal on morphological and biomolecular parameters of teeth and dental tissues was systematically examined. All methods tested showed significant changes in dental morphology and in the molecular integrity of DNA and the dental proteins, as revealed by aspartic acid racemisation (AAR). In forensic casework this may have severe impacts on the results of morphological methods (e.g. age estimation based on root translucency) and of biomolecular analyses (e.g. age estimation based on AAR and DNA analysis). Therefore, age estimation based on AAR should not be applied to tissue treated in such a manner, and it is recommended that teeth for analysis should be extracted before soft tissue removal. DNA in the hard tissue seems to be less susceptible to soft tissue removal than proteins, and several of the tested maceration techniques appear not to have a damaging effect on DNA. Generally, the indication for soft tissue removal demands a careful case management to avoid methodological collisions.
Adolescent↗
Increased alpha-linolenic acid intake increases tissue alpha-linolenic acid content and apparent oxidation with little effect on tissue docosahexaenoic acid in the guinea pig.
The essential fatty acids do not have identical roles in nutrition. Linoleic acid (LA) accumulates throughout the body of most mammals, whereas alpha-linolenic acid (ALA) is rarely found in tissue lipids to the same extent as LA. It has been argued that this is the result of metabolism of ALA to docosahexaenoic acid (DHA) or that ALA is rapidly beta-oxidized to acetyl CoA and CO2. In this study, we consider the effect of high and low ALA levels on the tissue distribution of ALA and other n-3 polyunsaturated fatty acids (PUFA) in all tissues. Guinea pigs were fed one of two defined diets for 3 wk from weaning with both diets containing 1.8% (by weight) of LA and either 1.7% ALA or 0.03% ALA. The high ALA diet was associated with significantly increased ALA levels in all tissues except the brain and significantly increased levels of long-chain n-3 PUFA in all tissues except intestines, brain, carcass, and skin. The long-chain n-3 PUFA content of the whole body was less than 5% of that of the ALA content in both diet groups, and the major long-chain n-3 PUFA (>66% of total) in the body was 22:5n-3. The brain was the only tissue where the DHA content exceeded that of 22:5n-3. On the low ALA diet, there appeared to be conservation of ALA based on a comparison of the ratio of LA to ALA in the tissues compared with that in the diet. On the high ALA diet there was a loss of ALA relative to LA in the tissues compared with the diet. These studies suggest that the low levels of tissue ALA in the guinea pig are likely the result of beta-oxidation or excretion via the skin and fur rather than metabolism to DHA.
Animals↗
Tissue-specific muscle, neural and liver stem/progenitor cells reside in the bone marrow, respond to an SDF-1 gradient and are mobilized into peripheral blood during stress and tissue injury.
Several reports imply that bone marrow hematopoietic stem cells transdifferentiate into tissue-specific stem cells; however, the possibility of committed tissue-specific stem cells pre-existing in the bone marrow has not been dealt with adequately. We present here an alternative explanation of the so-called phenomenon of stem cell transdifferentiation. First, we postulate that tissue-committed stem/progenitor cells circulate in the peripheral blood and compete for tissue-specific niches. The circulation of these cells plays an important physiological role in maintaining a pool of stem cells in distant parts of the body and the number of these cells in peripheral blood can be increased by the administration of agents similar to those used for mobilization of hematopoietic stem cells. Second, we postulate that bone marrow tissue is a source of various stem-cell chemoattractants and survival factors and provides an environment that chemoattracts tissue-specific circulating stem/progenitor cells. In this context, we envision bone marrow as a "home" or "hide-out place" not only of hematopoietic stem cells but also of already differentiated circulating tissue-specific stem/progenitors. In support of this concept, we report here that mRNA of several early markers for muscle (Myf-5, Myo-D), neural (GFAP, nestin) and liver (CK19, fetoprotein) is detectable in circulating (adherent cell-depleted) peripheral blood mononuclear cells. Moreover, using real-time RT-PCR, we found that the level of expression of these markers increases in the peripheral blood of humans and mice after mobilization by G-CSF. Furthermore, using stromal-derived factor-1 (SDF-1) chemotaxis and real-time RT-PCR analysis, we present evidence that early tissue-specific stem cells reside in normal human and murine bone marrow, express the CXCR4 receptor on their surface and can be highly enriched (in humans and mice) after chemotaxis to SDF-1 gradient. All our experiments were performed on freshly isolated cells to exclude the potential contribution of transdifferentiated hematopoietic stem or mesenchymal cells in the culture. We maintain that any transdifferentiation studies employing populations of bone marrow cells should rule out the possibility that the apparently pure hematopoietic stem cell population could in fact contain pre-existing tissue-specific stem/progenitors.
Animals↗
Increased pressure during retrograde cerebral perfusion in an acute porcine model improves brain tissue perfusion without increase in tissue edema.
BACKGROUND: There is a significant lack of scientific data to support the clinically accepted view that 25 to 30 mm Hg is the maximum safe perfusion pressure during retrograde cerebral perfusion (RCP). This study was designed to investigate whether perfusion pressure greater than 30 mm Hg during RCP is beneficial to the brain during prolonged HCA in an acute porcine model. METHODS: Sixteen pigs underwent 120 minutes of circulatory arrest in conjunction with RCP at a perfusion pressure of either 23 to 29 mm Hg (group L, n = 8) or 34 to 40 mm Hg (group H, n = 8) at 15 degrees C, followed by 60 minutes of normothermic cardiopulmonary bypass. Cortical blood flow and oxygenation were measured continuously with a laser flowmeter and near-infrared spectroscopy, respectively. Tissue water content was measured at the end of the experiments. RESULTS: Brain tissue blood flow was significantly higher in group H than in group L (16.8% +/- 4.1% vs 4.8% +/- 0.9% of baseline, p < 0.01) during RCP. Brain oxygen extraction in group L reached a maximum (approximately 70%) immediately after starting RCP, whereas in group H it increased gradually and reached a maximum at 120 minutes of RCP, indicating a greater supply of oxygen to tissue in group H than in group L. After RCP, the ability of brain tissue to use oxygen was better preserved in group H than in group L, as indicated by tissue oxygen saturation and the deoxyhemoglobin level. There was no significant increase in tissue water content in either group (group H 79.2% +/- 0.3%, group L 79.1% +/- 0.4%) relative to normal control pigs (78.7% +/- 0.1%). CONCLUSIONS: In this acute porcine model, increasing perfusion pressure from 23-29 to 34-40 mm Hg during RCP increases tissue blood flow and provides better tissue oxygenation, without increasing tissue edema. The optimal perfusion pressure for RCP needs to be further investigated.
Animals↗
Numbers of asbestos bodies on iron-stained tissue sections in relation to asbestos body counts in lung tissue digests.
Utilization of tissue digestion techniques has demonstrated the presence of large numbers of asbestos bodies within lungs of persons after occupational exposure to asbestos, and smaller numbers in the vast majority of persons with no identifiable exposure. Because of the wide variability in results of such studies among different observers, the presence of more than one asbestos body on light microscopy has been recommended recently as one of the morphologic requirements (together with peribronchiolar fibrosis) for the tissue diagnosis of asbestosis. However, data that correlate the occurrence of asbestos bodies in paraffin-embedded tissue sections with the quantification of asbestos bodies by tissue digestion techniques have not been available. The authors counted the asbestos bodies in multiple paraffin-embedded sections of lung tissues stained for iron, and compared those numbers with the asbestos body counts determined by hypochlorite digestion of wet formalin-fixed lung tissue in six cases of asbestosis or asbestos-associated neoplasia. When adjustments were made for asbestos body orientation in tissue sections, shrinkage of sections during processing, and conversion of lung volume to wet weight, the agreement between the two techniques was excellent (r = 0.98, P less than 0.001). An average of two asbestos bodies on 2 X 2 cm (4 cm2) iron-stained tissue sections 5 microns thick is equivalent to approximately 200 asbestos bodies per gram of wet fixed lung tissue.
Adult↗
Theoretical simulation of oxygen tension measurement in the tissue using a microelectrode: II. Simulated measurements in tissues.
BACKGROUND AND PURPOSE: The objectives of this study were to make a computer simulation of tissues with different vascular structures and to simulate measurements of oxygen tension using an Eppendorf-like electrode in these tissues and to compare the response to radiation of the tissues with the real oxygen distributions (called input distribution) with the response to radiation of the tissues in which the oxygen distribution is given by the results of the simulated measurements (called output distribution). MATERIALS AND METHODS: The structure of various tissues and the measurements of oxygen tension using a microelectrode were simulated using a computer program. The mathematical model used combines the description of a gradient of tissue oxygenation and the electrode absorption process. RESULTS: We have compared the oxygen distributions resulting from diffusion (input) with those obtained from a simulation of measurements (output) for various tissues in the same points. Because the electrode measurement is an averaging process, the calculated oxygen distributions are different from the expected ones and the extreme high and low values are not detected. We have then calculated the survival curves describing the response to radiation if there is a small fraction of truly hypoxic cells (expected values) or a large fraction of cells at intermediate values (observed results) in order to determine the differences between them. CONCLUSIONS: The results of our study show that oxygen electrode measurements do not give the true distribution of pO(2) values in the tissue. However, our results do not contradict the numerous empirical correlations between the Eppendorf measurements of tumour oxygenation and the outcome of treatments. Measurement results will be misleading for modelling purposes since they do not reflect the actual distributions of oxygen tensions in the measured tissue. Decisions based on such modelling could be very dangerous, especially with respect to the clinical response of tumours to new treatments.
Cell Hypoxia↗
OGG1 mRNA expression and incision activity in rats are higher in foetal tissue than in adult liver tissue while 8-oxo-2'-deoxyguanosine levels are unchanged.
This study was set up to investigate the relationships between the formation and removal of DNA damage in form of 8-oxodeoxyguanosine (8-oxodG) in neonatal (day 16 of gestation) as compared to adult rats. The hypothesis addressed was whether the rapidly dividing foetal tissue has an enhanced requirement of DNA repair providing protection against potentially mutagenic DNA damages such as 8-oxodG. The activity of the primary 8-oxodG-repair protein OGG1 was measured by a DNA incision assay and the expression of OGG1 mRNA was measured by Real-Time PCR normalised to 18S rRNA. The tissue level of 8-oxodG was measured by HPLC-ECD. We found a 2-3-fold increased incision activity in the foetal control tissue, together with a 3-15-fold increase in mRNA of OGG1 as compared to liver tissue from adult rats. The levels of 8-oxodG in the foetal tissue were unaltered as compared to the adult groups. To increase the levels of 8-oxodG, the rats received an injection (i.p.) of the hepatotoxin 2-nitropropane. The compound induced significant levels of 8-oxodG in male rat livers 5h after the injection and in the foetuses 24h after the injection, while the female rats showed no increase in 8-oxodG. The incision activity was slightly depressed in both male and female liver tissue and in the foetal tissue 5h after the injection, but significantly increased from 5 to 24h after the injection. However, it did not reach levels significantly above the control levels. In conclusion, this study confirms that foetal tissue has increased levels of OGG1 mRNA and correspondingly an enhanced incision activity on an 8-oxodG substrate in a crude tissue extract.
8-Hydroxy-2'-Deoxyguanosine↗
Elevated luteinizing hormone in serum, breast cancer tissue, and normal breast tissue from breast cancer patients.
PURPOSE: Hormones are known to be important in breast cancer, but studies have focused on steroid hormones and their cognate receptors. We report here an analysis of luteinizing hormone (LH) concentration in serum and breast tissue samples. MATERIALS AND METHODS: We studied serum and breast tissue samples from 353 women, 231 with breast cancer and 122 controls. Four breast tissue sites were sampled in every case. Tumor samples were also available from 48 patients and serum from 101 subjects. LH was measured by enzyme-linked immunosorbent assay. RESULTS: LH concentration in breast tissue was significantly higher in samples from patients with breast cancer than in samples from control subjects. In breast cancer patients, there was a decreasing gradiant from the cancer to the normal breast tissue, near and far from the tumor. Serum LH levels could not distinguish between breast cancer and control cases in most cases; but tissue LH could. CONCLUSIONS: LH concentrations were higher in breast tumors than in normal tissue near to or far from the tumor in women with breast cancer, and these concentrations were higher in women with breast cancer than in control cases. The different LH concentrations in breast tissue might be used to detect small or hidden carcinomas. In addition, the identification of luteinizing hormone in breast tissue offers a different explanation for the mechanism of action of LHRH agonists and might identify patients that respond to this treatment.
Adult↗
Characterization of the RF ablation-induced 'oven effect': the importance of background tissue thermal conductivity on tissue heating.
PURPOSE: To determine the effect of background tissue thermal conductivity on RF ablation heating using ex vivo agar phantoms and computer modelling. METHOD: Two-compartment cylindrical agar phantom models (5% agar, 5% NaCl, 3% sucrose) were constructed. These included a standardized inner compartment (2 cm diameter, 4 cm length, 0.25% agar) representing a tumour, surrounded by an outer compartment representing background tissue. The thermal conductivity of the outer compartment was varied from 0.48 W m-1 degrees Celsius (normal liver) to 0.23 W m-1 degrees Celsius (fat) by adding a fat-saturated oil-based solute (10-90%) to the agar. RF ablation was applied at 2000 mA current for 2 min. Temperatures were recorded up to 4 cm from the electrode tip at 1 cm intervals. Subsequently, a 2-D finite element computer model was used to simulate RF ablation of 2-24 min duration for tumours measuring 2-4 cm in diameter surrounded by tissues of different thermal conductivity with the presence or absence of perfusion (0-5 kg m-3 s-1) (n = 44). A comparison of results was performed. RESULTS: In agar phantoms, the amount of fat in the background tissue correlated with thermal conductivity as a negative exponential function (r2 = 0.98). Significantly increased temperatures were observed at the edge of the inner compartment (1 cm from the electrode tip) as the fat content of the outer compartment increased (p < 0.01). Thus, temperatures at 2 min measured 31.5 +/- 2.2 degrees Celsius vs 45.1 +/- 3.1 degrees Celsius for thermal conductivities of 0.46 W m-1 degrees Celsius (10% fat) and 0.23 W m-1 degrees Celsius (90% fat), respectively. On the other hand, higher levels of fat led to lower temperature increases in the background compartment (0.2 +/- 0.3 degrees Celsius for 90% fat vs. 1.1 +/- 0.05 degrees Celsius for 10% fat, p < 0.05). Phantom thermal heating patterns correlated extremely well with computer modelling (r2 = 0.93), demonstrating that background tissues with low thermal conductivity increase heating within the central tumour, particularly for longer durations of RF ablation and in smaller tumours. Furthermore, computer modelling demonstrated that increases in temperature at the tumour margin for background tissues of lower thermal conductivity persisted in the presence of perfusion, with a clinically relevant 4.5 degrees Celsius difference between background thermal conductivities of fat and soft tissue for a 3 cm tumour with perfusion of 2 kg m-3 s-1, treated for 12 min. CONCLUSION: Lower thermal conductivity of background tissues significantly increases temperatures within a defined ablation target. These findings provide insight into the 'oven effect' (i.e. increased heating efficacy for tumours surrounded by cirrhotic liver or fat) and highlight the importance of both the tumour and the surrounding tissue characteristics when contemplating RF ablation efficacy.
Agar↗
Effect of vascular endothelial growth factor and testis tissue culture on spermatogenesis in bovine ectopic testis tissue xenografts.
Bovine ectopic testis tissue grafting is a technique that can be used to study bovine spermatogenesis and for the production of germ cells for a variety of applications. Approximately 10% of seminiferous tubule cross sections in testis grafts contain spermatids, providing a unique tool to investigate what regulates germ cell differentiation. We hypothesized that manipulation of testis tissue grafts would increase the percentage of seminiferous tubule cross sections undergoing complete germ cell differentiation. To test this hypothesis, bovine testis tissue was treated with vascular endothelial growth factor (VEGF) at the time of grafting or explant cultured for 1 wk prior to grafting. For the VEGF experiment, 8-wk donor tissue and graft sites were treated with 1 microg of VEGF in order to increase angiogenesis at the graft site. For the testis tissue culture experiment, 4-wk-old donor testis was cultured for 1 wk prior to grafting to stimulate spermatogonial stem cell proliferation. Testis tissue grafts were removed from the mice 24 wk after grafting. VEGF treatment increased graft weight and the percentage of seminiferous tubule cross sections with elongating spermatids at the time of graft removal. Cultured testis tissue grafts were smaller and had fewer seminiferous tubules per graft. However, there was no difference in the percentage of seminiferous tubule cross sections that contained any germ cell type between groups. These data indicate for the first time that bovine testis tissue can be manipulated to better support germ cell differentiation in grafted tissue.
Animals↗
The effect of heparin on the regulation of factor VIIa-tissue factor activity by tissue factor pathway inhibitor.
Tissue factor pathway inhibitor (TFPI) inhibits factor VIIa-tissue factor and factor Xa through its first and second Kunitz-type domains, respectively. Previous studies have shown that heparin binds to TFPI at two sites and enhances the inhibitory activity of TFPI towards factor Xa. We have studied the effect of heparin of the TFPI-mediated inhibition of factor VIIa-relipidated tissue factor amiodolytic activity and factor VIIa-tissue factor proteolytic activity towards factor IX and factor X on a human bladder carcinoma cell line, J82. The inhibitory activity of full-length TFPI on factor VIIa-tissue factor amidolytic and proteolytic activities was greatly enhanced by heparin, whereas the inhibitory activity of a truncated form of TFPI lacking the third Kunitz-type domain and carboxy-terminal tail (TFPI1-161) was not affected by heparin. Optimal inhibition of factor VIIa-tissue factor by TFPI was observed at 0.1 U/ml heparin. Heparin enhanced the inhibitory activity of TFPI towards factor Xa even in the presence of factor VIIa-tissue factor complexes in solution phase. In addition, heparin augmented the ability of TFPI to inhibit factor VIIa-tissue factor amidolytic activity in the presence of active-site mutated factor X (S376A factor X). Our collective results suggest that heparin may play a significant role in augmenting the physiological regulation of factor VIIa-tissue factor activity by TFPI.
Animals↗
Relative biological effectiveness of ionizing radiations determined in tissue (RBE) fails in assessing comparative relative effectiveness in the tissue cells.
The value of the RBE of a test radiation is conventionally determined against a known standard radiation for a chosen response of a selected biological tissue and is expressed as the ratio of tissue absorbed doses at equal effect, or as ratio of magnitudes of the effect at equal absorbed dose. If such an effect is observable as a consequence of responses of individual elements of this tissue, namely the cells, such as induction of cancer that arises from a single cell, the relative biological effectiveness should be expressed as the ratio of the incidences of the effects at equal mean absorbed dose to the cells rather than at equal absorbed dose to tissue. This cell based relative biological effectiveness is here termed the relative local efficiency. Since tissue absorbed dose is a product of the number of energy deposition events in cells of that tissue (N(H)) and the mean absorbed dose to these cells in the exposed tissue (z(1)), per tissue mass equal tissue absorbed doses from different radiation qualities have different values of N(H) and z(1) As a result, for pink mutations in Tradescantia cells, the relative biological effectiveness of 0.43 MeV neutrons is 48 but the relative local efficiency in fact is 2.8.
Cells↗