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PubMed2004

Increased expression of thymidine phosphorylase in tumor tissue in proportion to TP-expression in primary normal tissue.

Thymidine phosphorylase (TP) is considered to be a key enzyme affecting the prognosis of patients with advanced gastrointestinal cancer. We tried to demonstrate the correlation of TP expression in tumor tissue and adjacent normal tissue, that is, primary normal tissue. The present study was designed to quantify TP level by enzyme-linked immunosorbent assay (ELISA) in tumor tissue and adjacent normal tissue obtained from 42 hepato-gastrointestinal cancer patients including 15 with gastric, 19 with colorectal and 8 with hepatocellular carcinomas. TP levels in tumor tissues were higher than those in adjacent normal tissues (p<0.001). There was a significant correlation between the expression of TP in tumor tissue and adjacent normal tissue (R=0.711, p<0.001; y=23.420+1.534x). On the other hand, there was no significant correlation between the ratio of tumor to adjacent normal tissue levels of TP (TP T/N) and expression of TP in tumor tissue (R=0.250, p=0.110). Thus, TP expression in tumor tissue may be high in proportion to TP expression in primary tissue. Furthermore, in clinical care, not only TP level in tumor tissue but also TP T/N value should be considered when using anticancer agents that become effective after conversion by TP to the active drug 5-FU.

Antimetabolites, Antineoplastic↗

PubMed2005

[The protein expression difference of transforming growth factor beta1, matrix metalloproteinases 1,7,9 and tissue inhibitors of matrix metalloproteinases-1 between chronic rhinosinusitis, nasal polyps and normal mucosa tissues].

OBJECTIVE: To compare the expression difference of transforming growth factor beta1 (TGF-beta1), matrix metalloproteinases1,7,9 (MMP-1,7,9 ) and tissue inhibitors of matrix metalloproteinases-1 (TIMP-1) protein among the chronic rhinosinusitis tissues, nasal polyps tissues and normal nasal mucosa tissues. METHOD: The protein expression of TGF-beta1, MMP-1, MMP-7, MMP-9 and TIMP-1 in chronic rhinosinusitis tissues from 22 patients, in nasal polyps tissues from 21 patients and in inferior turbinate tissues from 15 patients underwent nasal septum operation was detected by enzyme-linked immunosorbent assay (ELISA). RESULT: (1) In chronic rhinosinusitis and nasal polyps tissues, compared with controls, the expression of TGF-beta1, MMP-7, MMP-9, TIMP-1 protein was significant increased (P < 0.05); (2) The expression of TGF-beta1 and TIMP-1 in chronic rhinosinusitis tissues was significant increased versus that in nasal polyps tissues (P < 0.05); (3) Concentration of MMP-7 protein in nasal polyps tissues was found significant higher than that in chronic rhinosinusitis tissues (P < 0.01). CONCLUSION: Different TGF-beta1, MMP-7, TIMP-1 protein level in chronic rhinosinusitis and nasal polyps tissues might be the molecular basis of the different histopathological character of chronic rhinosinusitis and nasal polyp tissues.

Adolescent↗

PubMed2000

Grafting of neural tissue in chronically injured spinal cord: influence of the donor tissue on regenerative activity.

BACKGROUND: To determine the influence of different nervous tissue grafts on the regenerative activity of chronically injured spinal cord, an experimental study examining the expression of the proliferating cell nuclear antigen (PCNA) in chronically injured spinal cord subjected to neural grafting was performed. METHODS: Three months after induced spinal cord injury, paraplegic Wistar rats were subjected to grafting of neural tissue. Grafts consisted of fetal brain cortex, fetal spinal cord, crushed adult peripheral nerve tissue, or fetal brain cortex combined with crushed adult peripheral nerve tissue. Four months later, the spinal cord was removed and the grafted zone was studied by means of immunohistochemical demonstration of PCNA. RESULTS: Different patterns of PCNA expression were recorded in the different experimental groups. PCNA-immunostained cells in injured spinal cord tissue, mainly ependymal cells and astrocytes, increased when co-transplantation of fetal brain cortex and crushed adult peripheral nerve tissue was used, in comparison to other neural donor tissues. In the grafted tissue, proliferative activity was greater when fetal brain cortex, alone or with peripheral nerve, was used, in comparison to the use of fetal spinal cord or adult peripheral nerve tissue. Nevertheless, the number of PCNA-positive cells does not seem to be influenced by the presence of peripheral nerve tissue in the donor tissue. CONCLUSIONS: Our present findings suggest the effectiveness of co-transplantation of peripheral nerve tissue and fetal brain tissue in attempts at spinal cord reconstruction after injury.

Animals↗

PubMed1995

Comparison of the pharmacological response of human corpus cavernosal tissue with the response of rabbit cavernosal tissue.

1. This study directly compares the response of cavernosal tissue obtained from sexually mature rabbits with the response of human corpus cavernosal tissue obtained during implant surgery for psychogenic impotence (five individual samples) to field stimulation and specific autonomic agonists. 2. At 2 g basal tension, field stimulation of the rabbit corpus cavernosal tissue produced a frequency dependent biphasic response consisting of an initial relaxation followed by contraction. Low frequency stimulation induced primarily relaxations whereas high frequency stimulation induced primarily contractions. FS of human corpus cavernosal tissue induced a frequency dependent contraction. 3. In general, the rabbit corpus cavernosal strips showed a significantly greater degree of spontaneous activity than the strips of human cavernosal tissue. 4. Phenylephrine stimulated a rapid and sustained increase in basal tension in both tissues. Although the isolated strips weighed the same, the magnitude of the response of the rabbit tissue was significantly greater than the response of the human tissue. 5. For both tissues, FS relaxations were completely inhibited by L-NAME showing that the relaxations were mediated by nitric oxide. Similarly, for both tissues, nitroprusside, ATP, and bethanechol induced similar dose-response relaxations of pre-stimulated tissue. 6. In conclusion, the major difference between the response of human and rabbit tissue to various forms of stimulation was that isolated strips of human corporal tissue responded to FS with contractions at all frequencies whereas the rabbit tissue responded to the relaxations at low frequencies of stimulation; a clear bi-phasic response at intermediate frequencies; and contraction at high frequencies.

Animals↗

PubMed2005

Apoptosis in non-tumorous adult human testis tissue. Comparison of so-called 'normal' testis tissues.

INTRODUCTION: Apoptosis seems to play an important role in tumorigenesis, prognosis and therapy of testicular tumors. To understand its biological significance, it is important to quantify the amount of apoptosis and to compare the rate of apoptosis to that of a normal, unaffected reference tissue. Usually tissue from the unaffected site of the testis in patients with testicular cancer or testis tissue from patients who underwent surgical castration due to prostate cancer is used as the reference tissue. However it is not known, if both tissues are equivocal with respect to their apoptotic index. The purpose of the study was to compare the two most often used reference tissues for the quantification of apoptosis in testicular tissues with regard to their apoptotic index. MATERIALS AND METHODS: The apoptotic indices of both tissues were compared, using two standard apoptosis detection methods, i.e. in situ end labeling and a morphological approach. RESULTS: The apoptotic index in testis tissue from patients who were surgically castrated for anti-hormonal treatment of prostate cancer was shown to be significantly higher than the apoptotic index of tumor free but tumor-associated testicular tissue of testis cancer patients. There was a strong relationship between the apoptotic index and the age of the patients. CONCLUSION: Although there might be genetic changes in the tumor-associated testicular tissue influencing the apoptotic index, it seems advisable to use tumor-associated tissue rather than testis tissue of patients with prostate cancer as the reference tissue, due to the significant age dependence of the apoptotic index.

Adult↗

PubMed1999

Host expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in normal colon tissue affects metastatic potential of colorectal cancer.

PURPOSE: To clarify the mechanism of cancer cell invasion, we paid close attention to the role of matrix metalloproteinases and tissue inhibitors of metalloproteinases in normal tissue that is located in the same organ as the cancer. METHODS: Samples were obtained from a tumor lesion and normal tissue in the resected large intestine of 59 patients with colorectal cancer, including 13 cases with liver metastasis (Group A) and 46 cases without liver metastasis (Group B). In each sample the expression of m-RNA for matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 was examined using reverse transcription-coupled polymerase chain reaction and southern hybridization. RESULTS: In normal colon tissue the expression rate of matrix metalloproteinase-2 in Group A (76.9 percent) was significantly higher than that of Group B (15.2 percent; P < 0.0001). Regarding the expression pattern of m-RNA of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in normal colon tissue, Group B included 24 cases with matrix metalloproteinase-2 negative, and tissue inhibitor of metalloproteinase-2 positive (24/46; 52.2 percent). Conversely, Group A had only one case with matrix metalloproteinase-2 negative and tissue inhibitor of metalloproteinase-2 positive (1/13; 7.7 percent; P = 0.0107). In addition, the ratio of cases with matrix metalloproteinase-2 positive and tissue inhibitor of metalloproteinase-2 negative in Group A was 30.8 percent (4/13), which was a significantly higher rate than that in Group B (3/46; 6.5 percent; P = 0.0170). CONCLUSION: We think that the expression pattern of m-RNA of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in normal colon tissue is closely related to liver metastasis in colon cancer patients.

Aged↗

PubMed2006

Acellular biological tissues containing inherent glycosaminoglycans for loading basic fibroblast growth factor promote angiogenesis and tissue regeneration.

It was found in our previous study that acellular tissues derived from bovine pericardia consist primarily of insoluble collagen, elastin, and tightly bound glycosaminoglycans (GAGs). It is speculated that the inherent GAGs in acellular tissues may serve as a reservoir for loading basic fibroblast growth factor (bFGF) and promote angiogenesis and tissue regeneration. This study was therefore designed to investigate effects of the content of GAGs in acellular bovine pericardia on the binding of bFGF and its release profile in vitro while its stimulation in angiogenesis and tissue regeneration in vivo were evaluated subcutaneously in a rat model. To control the content of GAGs, acellular tissues were treated additionally with hyaluronidase for 1 (Hase-D1), 3 (Hase-D3), or 5 days (Hase-D5). The in vitro results indicated that a higher content of GAGs in the acellular tissue resulted in an increase in bFGF binding and in a more gradual and sustained release of the growth factor. The in vivo results obtained at 1 week postoperatively showed that the density and the depth of neo-vessels infiltrated into the acellular tissue loaded with bFGF (acellular/bFGF) were significantly greater than the other test samples. At 1 month postoperatively, vascularized neo-connective tissues were found to fill the pores within each test sample, particularly for the acellular/bFGF tissue. These results suggested that the sustained release of bFGF from the acellular/ bFGF tissue continued to be effective in enhancing angiogenesis and generation of new tissues. In conclusion, the inherent GAGs present in acellular tissues may be used for binding and sustained release of bFGF to enhance angiogenesis and tissue regeneration.

Absorbable Implants↗

PubMed1998

Tissue distribution, turnover, and glycosylation of the long and short growth hormone receptor isoforms in rat tissues.

Two isoforms of the GH receptor, the full-length receptor (GHRL) and a short isoform (GHRS) that lacks the transmembrane and intracellular domains of GHRL, have been analyzed in rat tissue extracts by Western blotting and immunoprecipitation. Although quantitative estimates of GHRS and GHRL based on coprecipitation of [125I]GH indicated similar amounts of both isoforms in tissue extracts, the 110 kDa band corresponding to GHRL was generally not detected on Western blots without enrichment by immunoprecipitation. Two bands with electrophoretic mobilities corresponding to 38 and 42 kDa were present in extracts prepared from liver, muscle, and adipocytes. Western blots of the GH binding protein in rat serum also revealed two bands, but these had electrophoretic mobilities corresponding to 44 and 52 kDa. After digestion by endoglycosidase F, a single band with an electrophoretic mobility corresponding to 31 kDa was detected in samples from adipocytes, liver or serum, indicating that GHRS retained in tissues is glycosylated less extensively than that in rat serum. Digestion with neuraminidase indicated that the smaller glycoproteins in tissue extracts lack sialic acid residues that are present in serum samples. Furthermore, endoglycosidase H degraded GHRS in liver extracts to a 31 kDa band but did not degrade serum samples, suggesting that tissues retain a high mannose form of GHRS. The abundance of GHRS or GHRL in tissues from male, virgin female, and pregnant rats was estimated from the amount of 125I-GH that was bound to each isoform after immunoprecipitation. Liver contained more than 10 times as much GHRS per gram of tissue as fat or muscle. In liver, muscle, and fat, the amount of GHRS exceeded that of GHRL, sometimes by as much as 6-fold. GHBP levels in serum of females exceeded those in males, and rose even higher in pregnant females. The abundance of GHRS in all tissue extracts paralleled serum levels. In muscle and fat, the levels of GHRL did not differ in male, female and pregnant rats, whereas in liver, the pattern was similar to the GHRS pattern. In all tissues, pools of GHRS exceeded those of GHRL by a factor that grew larger as tissue and serum levels increased. The half life of GHBP in serum was estimated to be 2.4 h in rats treated with cycloheximide, whereas that of GHRS was 20 min in liver and 8.5 h in fat. These results suggest that GHRS is synthesized in liver 8 times faster than it is released into serum, whereas synthesis in fat is less than 30% of the rate at which it is released into serum by all tissues. Therefore, liver appears to be the major source of GHBP in serum. Although secretion into the circulatory system accounts for little or perhaps none of its turnover in some tissues, GHRS pools in tissues do appear to be regulated, suggesting that GHRS may function primarily in the cells in which it is synthesized.

Adipocytes↗

PubMed1997

A comparative study of root coverage obtained with guided tissue regeneration utilizing a bioabsorbable membrane versus the connective tissue with partial-thickness double pedicle graft.

Obtaining predictable root coverage has become an important part of periodontal therapy. The purpose of this study was to compare two techniques of obtaining root coverage. The two techniques were the connective tissue with partial-thickness double pedicle graft and guided tissue regeneration with a bioabsorbable polylactic acid softened with citric acid ester membrane. The connective tissue with partial-thickness double pedicle graft had a mean root coverage of 97.1%, and the guided tissue regeneration procedure produced a mean root coverage of 75.1%. This difference was not statistically significant. Additionally, it was the goal of this study to determine if the thickness of the tissue near the defect was a factor in root coverage. Thickness of the tissue was not a factor with the connective tissue with partial-thickness double pedicle graft. The thin areas had a mean root coverage of 100%, while the others had a mean root coverage of 95.9%. This difference was not statistically significant; however, the thickness of the tissue was a factor in root coverage success in the guided tissue regeneration procedure. The thin areas treated with guided tissue regeneration had a mean root coverage of 26.7%, while the others had a mean root coverage of 95.9%. This difference was statistically significant. The results of this study demonstrate that root coverage is possible with both procedures. However, when the tissue in the area of the defect is relatively thin, the connective tissue with partial-thickness double pedicle graft will produce greater root coverage. When treating defects with tissue that is not thin, similar amounts of root coverage can be obtained with both procedures.

Absorption↗

PubMed1981

Fatty acid synthesis in mouse brown adipose tissue. The influence of environmental temperature on the proportion of whole-body fatty acid synthesis in brown adipose tissue and the liver.

Fatty acid synthesis has been measured in vivo with 3H2O in mice acclimated at different environmental temperatures (33, 22, 4 degrees C), and the importance of brown adipose tissue and the liver to whole-body fatty acid synthesis at each temperature assessed. At 33 degrees C, when non-shivering thermogenesis is minimal, the rate of fatty acid synthesis in interscapular brown adipose tissue was lower than in the liver, but higher than in white adipose tissue and the carcass. At 4 degrees C, when non-shivering thermogenesis is maximal, the fatty acid synthesis rate in interscapular brown adipose tissue was many times greater than in any other tissue. High fatty acid synthesis rates were also found in other brown adipose tissue depots--subscapular, dorsocervical and axillary--of cold-acclimated mice. In mice maintained at 22 degrees C the rate of fatty acid synthesis was also higher in brown adipose tissue than in other tissues. Overall, the relative importance of brown adipose tissue as a site of fatty acid synthesis increased with lower environmental temperatures, while that of the liver decreased. It was calculated that brown adipose tissue in total accounted for approx. 5% of whole-body fatty acid synthesis at 33 degrees C, 10% at 22 degrees C and 30% at 4 degrees C. In contrast, hepatic synthesis amounted to 32% of whole-body fatty acid synthesis at 33 degrees C, 16% at 22 degrees C and only 11% at 4 degrees C. An estimate of the contribution that de novo synthesis makes to total fatty acid utilization by interscapular brown adipose tissue suggests that fatty acid synthesis and breakdown constitutes a significant heat-dissipating 'cycle' in brown adipose tissue of cold-acclimated mice. Such a cycle is not evident in suckling animals since fatty acid synthesis in brown adipose tissue is very low during early development.

Adaptation, Physiological↗

PubMed2000

Cytokine profiles in eye muscle tissue and orbital fat tissue from patients with thyroid-associated ophthalmopathy.

Eye muscle (EM) and retroorbital fat tissue are two major sites of involvement in thyroid-associated ophthalmopathy (TAO). Lymphocytic infiltration in these tissues is a prominent histological feature of TAO. We have investigated the cytokine gene profiles in EM and orbital fat (OF) tissues from patients with TAO. Total RNA was isolated from EM tissue of 14 patients and from OF tissues of 29 patients with TAO. Cytokine gene expression was assessed by RT-PCR using paired primers for interferon gamma (IFNgamma), tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, CD4, CD8, and glyceraldehyde-3-phosphate dehydrogenase. IFNgamma, TNFalpha, IL-1beta, and IL-6 messenger RNA (mRNA) were mainly detected in EM tissue, whereas IL-4 and IL-10 mRNA were detected in only one patient. On the other hand, in OF tissue, IL-4 and IL-10 mRNA were detected in 24% and 38% of the patients, respectively, and IFNgamma, IL-1beta, and IL-6 mRNA were less often detected compared with EM tissue. The enlargement of EM tissue as assessed by computed tomography correlated significantly with TNFalpha mRNA expression in EM tissue. The orbital volume was positively correlated with IL-6 mRNA expression and negatively correlated with IL-4 mRNA and IL-10 mRNA expression in OF tissue. These results suggest that T helper (Th) 1-like cytokines predominate in EM tissue in most patients and that the predominant cytokine profile in OF tissue varies from patient to patient. Both Th1-like and Th2-like immune responses may play roles in the development of two components of ophthalmopathy.

Adipose Tissue↗

PubMed2003

A microdissection and molecular genotyping assay to confirm the identity of tissue floaters in paraffin-embedded tissue blocks.

CONTEXT: A recurring problem in surgical pathology practice is specimen mix-up and floater contamination. While many cases can be resolved histologically, a significant number remain unclear and may have serious clinical and medicolegal implications. OBJECTIVES: To design a microdissection and genotyping assay to identify contaminating floater tissues in paraffin-embedded tissues that is optimized for small samples, and to use the assay to resolve a series of clinical cases with floater tissues. MATERIALS AND METHODS: Twenty-one cases of possible tissue floater contamination in paraffin-embedded tissue blocks were included. Using 4 unstained, 4-microm-thick histologic sections, multiple sites were microdissected under direct visualization either by hand or by laser capture microdissection. Nonneoplastic and neoplastic tissues were sampled. Polymerase chain reaction was performed for a panel of 10 polymorphic microsatellite markers at 1p34, 3p26, 5q21, 9p21, 10q23, and 17p13. Allele size and content were analyzed semiquantitatively by fluorescent capillary electrophoresis, and the genotypes for the tissues in the paraffin-embedded tissue blocks were compared for identity. RESULTS: Tissue identification was successful in all cases, despite small tissue sample size and fixation effects. Comparative analysis of neoplastic tissue floaters and the presumptive source tumor was performed when possible to control for possible allelic loss or microsatellite instability. CONCLUSIONS: Microdissection and genotyping are effective and reliable means to objectively resolve problems of possible floater contamination. Even minute tissue samples provide sufficient DNA template for polymerase chain reaction microsatellite analysis. Because of the potential clinical implications of floaters, we recommend that all suspected floaters that would change a diagnosis from benign to malignant be subjected to genotyping assay to confirm the identity of the floater tissue.

Biopsy↗

PubMed1990

Pharmacokinetics of antibiotics in tissues and tissue fluids: a review.

The majority of bacterial infections occur outside the vascular compartment and, thus, considerable interest has been devoted to studies of antibiotic concentrations in different tissues. This review deals with the pharmacokinetics of antibiotics in tissues where the drug is distributed by passive diffusion. It is not always recognized that tissue levels of antibiotics represent the means of different concentrations in the major tissue compartments: interstitial fluid, cells and blood capillaries. Non-lipophilic drugs, such as beta-lactam antibiotics, which do not penetrate cells, are confined to the extracellular fluid volume, which constitutes approximately 20% of the tissue. Consequently, whole tissue levels are low. Conversely, drugs that penetrate and accumulate in cells may well yield tissue levels exceeding the serum levels. Since most bacterial infections start and progress in the interstitial fluid, whole tissue levels are therapeutically meaningless, but are nevertheless often compared to the MICs of bacteria. For protein-bound drugs, the lower albumin concentrations in extracellular fluids is another important factor that may lead to erroneous conclusions regarding the ability of an antibiotic to distribute into tissues. Different models have been developed to study antibiotic levels in the interstitial fluid. The geometry of the tissue fluid compartment (ratio of surface area to volume: SA/V) has been recognized as one of the most important determinants of antibiotic pharmacokinetics in these models. In healthy tissues (high SA/V) similar concentrations are found in serum and tissue fluid. Although limited information is available regarding antibiotic pharmacokinetics in infected tissues, it seems that in acute bacterial infections, the most relevant concentrations to relate to pharmacodynamic parameters are the unbound levels of the drug in serum.

Albumins↗

PubMed1996

Temperature-controlled laser photocoagulation of soft tissue: in vivo evaluation using a tissue welding model.

BACKGROUND AND OBJECTIVES: Laser surgical procedures involving photocoagulation of soft tissue have relied on subjective visual endpoints. The thermal damage to the denatured tissue in these procedures is highly dependent on the tissue temperatures achieved during laser irradiation. Therefore, a system capable of real time temperature monitoring and closed loop feedback was used to provide temperature controlled photocoagulation (TCPC). STUDY DESIGN/MATERIALS AND METHODS: The TCPC system consisted of a 1.32 microns Nd:YAG laser, an infrared thermometer, and a microprocessor for data acquisition and feedback control. A porcine skin model was used. Tissue welds were completed to evaluate the photocoagulation effects at different predetermined temperatures. A quantitative measurement of tissue photocoagulation was obtained by tensile strength measurements of the laser repairs. Histology of the irradiated tissue was used to determine the extent of thermal injury associated with different photocoagulation temperatures. RESULTS: The TCPC system was capable of maintaining a relatively constant temperatures (+/- 4 degrees C) during laser irradiation. The tensile strengths of acute repairs increased with temperature over the range studied (65-95 degrees C). Tensile measurements made after several days of healing showed that higher temperature (95 degrees C) welds had lower strengths than repairs completed at lower (65 degrees C or 75 degrees C) temperatures and were significantly lower at 3 days. Acute histology showed that the amount thermal damage was strongly dependent on the tissue temperature and increased both in tissue depth and lateral to the repair with temperature. The histologic results suggest that the increase in the acute repair tensile strength as the weld temperature increased was due to an increase in the depth of tissue photocoagulation. The increase in the lateral tissue injury measured histologically for higher temperature welds likely resulted in the decreased chronic tensile strengths, as a healing response to excessive thermal damage. CONCLUSION: Tissue temperatures can be controlled during laser photocoagulation of skin. The degree of acute and chronic tissue damage is highly dependent on the temperature during welding. By controlling the tissue temperature during laser procedures, the surgical outcome can be more reliably predicted and reproduced, as compared to the conventional open loop methods. In addition, the use of a TCPC system should significantly reduce the learning curve for photothermal surgical procedures.

Animals↗

PubMed1980

Tissue compliance in superficial tissues along body axis in man.

A previously described miniature plethysmograph which allowed the measurement of tissue volumes in superficial tissues was enclosed in a small plexiglass chamber and attached to the frontal area, sternum, dorsum and the tibia. The tissues interposed between bone and skin underneath the chamber were exposed to pressures between +/- 3 and +/- 15 mmHg in order to test tissue deformability. The pressure application induced within the first 5 s a fast component of tissue deformation comprising between 75-90% of the total deformation followed by a slow component which lasted till the end of the pressure application. The highest deformability was found in the tissues of the sternum and dorsum whereas the stiffest tissues were in the pretibial area. Assuming the tissue deformation is due to a translocation of fluid into or out of the pressurized tissue, the tissue compliance was calculated. This calculated tissue compliance was 19.2 ml . 1,000 ml-1 . mmHg-1 in the sternum and 6.4 ml . 1,000 ml-1 . mmHg-1 (P < 0.01) in the pretibial area applying a pressure of +/- 3 mmHg. The differences observed are due to the morphological arrangement of the tissue fibres which in turn have to counteract the gravity forces to which the tissues are usually exposed during upright standing.

Animals↗

PubMed1984

Characterization of proton NMR relaxation times in normal and pathological tissues by correlation with other tissue parameters.

To help understand which tissue parameters best account for the water proton NMR relaxation times, the longitudinal relaxation time (T1), the transverse relaxation time (T2), and the water content of 16 tissues from normal adult rats were measured at 10.7 MHz and 29 degrees C. Regression analyses between the above and other tissue parameters were performed. These other tissue parameters included: the amounts of various organic and inorganic components, protein synthetic rate, oxygen consumption rate, and morphological composition. In addition, the differences in T1, T2, and water content values between normal liver and malignant tumor (Morris #7777 a transplantable hepatoma) were studied to help understand how a disease state can be detected and characterized by NMR spectroscopy. The results of this study and information from the literature allow the following generalizations to be made about tissue T1 and T2 values: (1) Each normal tissue has rather consistent and characteristic T1 and T2 relaxation times which are always shorter than the T1 and T2 of bulk water; (2) tissues with higher water content tend to have longer T1 relaxation times; (3) tissue T2 values are not, however, as well correlated with water content as T1 values; (4) tissues with shorter T1 values have higher calculated hydration fractions, greater amounts of rough endoplasmic reticulum, and a greater rate of protein synthetic activity; (5) tissues with higher lipid content, associated with intracellular non-membrane bounded lipid droplets, tend to have longer T2 values; (6) tissues with greater overall surface area, whether in the form of cellular membranes or intracellular or extracellular fibrillar macromolecules, tend to have shorter T2 values; (7) the differences between T1 and T2 values between tumor and normal tissues correlated with differences in the volume fraction (amounts) of extracellular fluid volumes and in the amounts of membrane and fibrillar surface area in the cells. The above generalizations should be useful in predicting T1 and T2 changes associated with specific tissue pathologies.

Amino Acids↗

PubMed1990

An instructive role for the interstitial matrix in tissue patterning: tissue segregation and intercellular invasion.

Intercellular invasion is the intrusion of the cells of one tissue into space occupied by a second tissue. The alternative situation to invasion, one characteristic of most coherent tissues, is segregation, with identifiable boundaries existing between contiguous tissues. The interfaces between mesenchymal and myocardial tissues in the developing avian heart show a profoundly different character in different regions of the heart: the interface between epicardial mesenchyme and heart wall myocardium is planar, without intermingling of the two cell types, whereas the interface between endocardial cushion mesenchyme and myocardium is diffuse, with extensive invasion of both tissue types across the border to produce intermingling of the two tissues. Thus, invasion and tissue segregation coexist in different regions of the mesenchyme-myocardium contact zone. Investigation of the involvement of the interstitial matrix in invasion and segregation has been conducted by maintaining the two tissues in mutual contact in organ culture. Investigation of the mechanisms by which the two cell types sort out in randomized chimeric tissue reaggregates has provided insight into the conditions for tissue segregation. We have modeled invasion in organ culture by fusing aggregates of myocardial cells with aggregates of cardiac mesenchymal cells. Cells of both tissues invaded the partner aggregate during a period of 1-3 d of coculture. Both invasion and segregation in the aggregates appear to depend on the presence or absence of a fibronectin-rich interstitial matrix elaborated by the cardiac mesenchyme. During sorting, the matrix appears selectively in regions occupied by the mesenchyme. Under conditions of culture that are nonpermissive for matrix deposition, sorting fails to occur. Stimulation of matrix deposition by addition of serum, transforming growth factor beta, or isolated matrix itself is accompanied by sorting out of the two tissues. Sorting out is blocked reversibly by inclusion of the fibronectin adhesion site peptide, GRGDSP. Invasion of fused aggregates is preceded by a redistribution of the fibronectin-containing matrix of the mesenchymal aggregate such that matrix-poor regions come to occupy the interface with the myocardial partner aggregate. The invasion that ensues involves mesenchymal cells emigrating from, and myocardial cells intruding into, matrix-poor regions of the mesenchymal aggregate.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

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↗