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Myocardial tissue motion influence on laser Doppler perfusion monitoring using tissue Doppler imaging.

Tissue motion of the beating heart generates large movement artifacts in the laser Doppler perfusion monitoring (LDPM) signal. The aim of the study was to use tissue Doppler imaging (TDI) to localise intervals during the cardiac cycle where the influence of movement artifacts on the LDPM signal is minimum. TDI velocities and LDPM signals were investigated on three calves, for normal heartbeat and during occlusion of the left anterior descending coronary artery. Intervals of low tissue velocity (TDIint, < 1 cm s(-1)) during the cardiac cycle were identified. During occlusion, these intervals were compared with low LDPM signal intervals (LDPMint, <50% compared with baseline). Low-velocity intervals were found in late systole (normal and occlusion) and late diastole (normal). Systolic intervals were longer and less sensitive to heart rate variation compared with diastolic ones. The overlap between LDPMint and TDIint in relation to TDIint length was 84+/-27% (n = 14). The LDPM signal was significantly (p < 0.001, n = 14) lower during occlusion if calculated during minimum tissue motion (inside TDIint), compared with averaging over the entire cardiac cycle without taking tissue motion into consideration. In conclusion, movement artifacts are reduced if the LDPM signal is correlated to the ECG and investigated during minimum wall motion. The optimum interval depends on the application; late systole and late diastole can be used.

Animals↗

Melanin granule models for the processes of laser-induced thermal damage in pigmented retinal tissues. I. Modeling of laser-induced heating of melanosomes and selective thermal processes in retinal tissues.

The computer modeling was applied for investigation of the processes of laser-induced tissue damage. The melanin granule models for the processes of laser-induced thermal damage and the results of computer modeling of the optical, thermophysical, and thermochemical processes during selective laser interaction with melanoprotein granules (melanosomes) in retinal pigment epithelium are presented in this paper. Physical-mathematical model and system of equations are formulated which describe thermal interaction processes for "short" laser pulses of duration t (p)<10(-6) s and for " long' pulses of duration t(p) > 10(-6) s. Results of numerical simulation of the processes give the space-time distributions of temperature and degrees of thermodenaturation of the protein molecules inside and around melanosomes and in the volume of irradiated tissues. Energy absorption, heat transfer and thermochemical (thermodenaturation, coagulation) processes occurring during the interaction of laser pulses with pigmented spherical and spheroidal granules in heterogeneous tissues are theoretically investigated. The possibility for selective interaction of short laser pulses with pigmented granules is discussed which results in the formation of denaturation microregions inside and near the pigmented granules (granular thermodenaturation) without origination of a continuous macroscopic thermodenaturation lesion in tissue. Analytical model of heating of single spherical and spheroidal granule under laser pulse is presented. Simple equations for time dependencies of particle temperature are obtained. The presented results are of essential interest for laser applications in and can be used for investigation of laser interaction with pigmented tissues in different fields of laser medicine.

Computer Simulation↗

Pregnancy-induced changes in the fibrinolytic balance: evidence for defective release of tissue plasminogen activator and increased levels of the fast-acting tissue plasminogen activator inhibitor.

Pregnancy is accompanied by an increased risk of thromboembolic disease. One contributing factor to such disease in the nonpregnant patient is disordered fibrinolysis. It has been suggested that defective fibrinolysis may occur in pregnancy, but this defect has been poorly characterized. In the present study of 52 women with normal pregnancies and 56 nonpregnant control women, we found a marked change in levels of releasable tissue plasminogen activator in pregnant women beginning in the first trimester. Whereas nonpregnant women demonstrated releasable levels of tissue plasminogen activator of 0.74 +/- 0.15 IU/ml of plasma, in the pregnant women the amount released was only 0.06 +/- 0.02 IU/ml of plasma (p less than 0.01). These levels were observed beginning in the first trimester. Levels of the recently described fast-acting tissue plasminogen activator inhibitor increased significantly throughout pregnancy. Values ranged from 8.40 +/- 0.27 IU/ml of plasma in the first trimester to 9.92 +/- 0.09 IU/ml of plasma in the third trimester (p less than 0.05) compared with the level of 8.46 +/- 0.19 IU/ml of plasma in nonpregnant subjects. These data suggest that alterations both in releasable tissue plasminogen activator and in the fast-acting tissue plasminogen activator inhibitor contribute to the physiologic hypercoagulable state of pregnancy.

Adult↗

Tissue distribution and mode of DNA methylation in mice by methyl methanesulphonate and N-methyl-N' -nitro-N-nitrosoguanidine: lack of thymic lymphoma induction and low extent of methylation of target tissue DNA at 0-6 of guanine.

The methylating agents methyl methanesulphonate (MMS) and N-methyl N'-nitro-N-nitrosoguanidine (MNNG), administered by single i.p. injection in mice failed to yield thymic lymphoma at doses around 60% of the LD50 values, in contrast to MNUA which gives a high yield of tumours by this route. Comparison of the tissue distribution and mode of DNA methylation by these agents showed a positive correlation with ability to methylate the 0-6 atom of guanine in DNA of the target tissues thymus and bone marrow and tumorigeneis. MMS gave a low yield of this product due to its relatively low Sn1 reactivity but was able to methylate DNA extensively at other sites in the target tissues and other organs examined. MNNG despite its ability to methylate 0-6 of guanine in DNA in vitro to the same relative extent as the potent carcinogen MNUA, methylated DNA of thymus and bone marrow to a very small extent in vivo but was able to methylate DNA in certain other tissues nearer the site of i.p. injection. These findings contrast with the general relatively extensive methylation of 0-6 of guanine in DNA of the target tissues and other organs by N-methyl-N-nitrosourea (MNUA).

Animals↗

In vitro studies on steroid metabolism by gonadal tissues from ambisexual teleosts. II. Conversion of [14C]androstenedione by the heterologous gonadal tissues of the protandric sea bream Pagellus acarne (Risso).

The heterologous gonadal tissues of the protandric sea bream Pagellus acarne were incubated with [14C]androstenedione in vitro. The tissues were taken from two males, an inverting specimen, and a female in early April. Although the testicular tissue regresses in the inverting fish the rate of 11 beta-hydroxylation in the male part of the gonad is at least as high as in the homologous portion of the "pure" male. No difference was found in the enzymatic pattern between the ovarian part of the inverting animal and that of the female. There is, however, a striking distinction in the metabolic activities of the pooled ovarian parts from two males and the homologous tissues from the inverting and female animals. They concern mainly the activities of 11 beta-hydroxylase and 17 beta-HSD. Moreover, ring A-reduction and the ratio of 5 alpha/5 beta-reduced metabolites differ considerably from the corresponding gonadal tissues taken from the inverting and the female specimen. The possible physiological meaning of these findings remains to be elucidated.

Animals↗

Continuous chromogenic tissue factor assay: comparison to clot-based assays and sensitivity established using pure tissue factor.

The continuous chromogenic tissue factor assay has been compared to one-stage and two-stage coagulation assays, and its sensitivity has been established using purified human placental tissue factor. Log-log plots of the clot-times versus A405/min2 are linear over the mutually useful ranges of tissue factor concentration. Using human placental tissue factor reconstituted into phosphatidylserine-phosphatidylcholine (30:70) vesicles, the chromogenic assay quantitatively detected tissue factor in dilutions containing from 3 femtomoles to less than 10 attomoles of protein.

Animals↗

Formation of tissue factor activity following incubation of recombinant human tissue factor apoprotein with plasma lipoproteins.

Incubation of recombinant human tissue factor apoprotein (Apo-TF) with human plasma decreased the recalcified clotting time of this plasma in a time-and dose-dependent manner suggesting relipidation of the Apo-TF by plasma lipoproteins. Incubation of Apo-TF with purified preparations of human very low density, low density and high density lipoproteins resulted in tissue factor activity in a clotting assay. The order of effectiveness was VLDL greater than LDL much greater than HDL. Tissue factor activity generated by incubation of a fixed amount of Apo-TF with plasma lipoproteins was lipoprotein concentration-dependent and saturable. The association of Apo-TF with lipoprotein particles was supported by gel filtration studies in which 125I-Apo-TF coeluted with the plasma lipoprotein in the void volume of a Superose 6 column in the presence and absence of calcium ions. In addition, void-volume Apo-TF-lipoprotein fractions exhibited tissue factor activity. These results suggest that the factor VIII-bypassing activity of bovine Apo-TF observed in a canine hemophilic model may be due, in part, to its association with plasma lipoproteins and expression of functional tissue factor activity.

Apoenzymes↗

Eicosanoid production by intrauterine tissues before and after labor in short-term tissue culture.

Prostanoid production by intrauterine tissues from pregnant and non-pregnant women has been studied intensively over the last decade. Little is known about the lipoxygenase metabolites of arachidonic acid (AA). The production of prostaglandins and HETEs by pregnancy specific human tissues was investigated in a short-term culture system. Tissue samples were obtained after uncomplicated pregnancies from placenta, fetal membranes and decidua of deliveries before (n = 6) and after the onset of labor (n = 8) and incubated for 1 hour in oxygenated HBSS. In the supernatant, PGE2, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 were measured with RIA and 15-, 12- and 5-HETE with HPLC and UV-detection. The main AA-metabolite in all tissue incubations was 12-HETE. Decidua produced 12 to 28 times more prostaglandins than placenta and fetal membranes with 6-keto-PGF1 alpha as the main metabolite. The main cyclooxygenase derivative measured from placenta and fetal membrane incubations was TXB2. After labor, fetal membranes showed an increase in total prostaglandin (significant for PGE2) and a decrease in HETE synthesis. The physiologic significance of 12-HETE in reproduction is still poorly understood, but a shift in AA metabolism from HETEs to prostaglandins may be involved in the initiation of labor. Furthermore, these results point to different roles of the tissue compartments within the pregnant uterus for the parturition process.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Pharmacokinetics of mitomycin-C in plasma and tumor tissue of cervical cancer patients and in selected tissues of female rats.

Mitomycin-C (MMC) is an alkylating agent which has shown significant activity in gynecologic cancers, both in vivo and in vitro. We determined the delivery of MMC to target tissue by comparing plasma and tumor tissue concentrations of MMC as measured by high-performance liquid chromatography (HPLC) in five patients with cervical cancer. In a companion study, we measured MMC concentrations in plasma and selected tumors of female rats given an equivalent dose. In patients, the mean terminal half-life and total body clearance rates of MMC were 40 min and 275 ml/min/m2, respectively. The mean cervical tumor to plasma concentration of MMC was 1.26 +/- 0.34 (mean +/- SE, n = 4). In female rats, the terminal half-life and total body clearance rates of MMC were 28.4 min and 270 ml/min/m2, respectively. Tissue concentrations of MMC in rats were lower than plasma concentrations measured at corresponding times. The highest concentrations were found in lung and uterus (including cervix) with lower concentrations in ovary and liver. The mean half-life for elimination of MMC from tissues of rats was 20.3 +/- 2.8 min (mean +/- SE, n = 6). Based on similar pharmacokinetic parameters in rats and patients, the rat appears to be a suitable model for the disposition of MMC in human patients. The near equivalent drug concentrations found in tumor and plasma of patients suggests that the in vitro tests conducted at concentrations based on plasma level may be relevant to cervical tumor tissue, as well.

Adenocarcinoma, Mucinous↗

Changes in sulfated mucopolysaccharide composition of mammalian tissues during growth and in cancer tissues.

The distribution of sulfated mucopolysaccharides in different tissues during growth and in cancer tissues is reported. It is shown that most of the tissues of 1 day-old rats and rabbits contain chondroitin sulfate A/C, chondroitin sulfate B and heparan sulfate in about the same proportions, whereas in adult animals chondroitin sulfate A/C decreases in concentration or disappears. Changes in the relative proportions of chondroitin sulfate B and heparan sulfate were also observed in most of the tissues. In rats, these changes occur in the first 25 days of extrauterine development. A great increase of chondroitin sulfate A/C was observed in human tumors of different origins when compared with the normal adjacent tissues. Changes in the relative proportions of chondroitin sulfate B and heparan sulfate were also observed in most of the tumors analysed. The possible role of chondroitin sulfate A/C in cell division is discussed in view of the present findings.

Aging↗

A quantitative analysis of rat adrenal chromaffin tissue: morphometric analysis at tissue and cellular level correlated with catecholamine content.

A morphometric analysis of normal Wistar rat adrenal medulla following perfusion fixation and Araldite embedding, was correlated with catecholamine levels on fresh tissue, measured by high-performance liquid chromatography. The mean volume of whole adrenal is 13.2 mm3 and the mean medullary volume 1.3 mm3. Volume density estimates showed that the medulla is composed of 63% chromaffin tissue with an adrenaline to noradrenaline storing cell ratio of 4.4:1. The vasculature occupies 20%, neuronal tissue 5% and interstitial tissues 12% of the medulla. A comparison was made of cell volumes, cell numbers and volume and surface density estimates of cytoplasmic organelles in adrenaline and noradrenaline storing cells. The mean cell volume of adrenaline storing cells at 1300 micron3 is larger than that of noradrenaline storing cells at 980 micron3. A single adrenal medulla contains 4.4-5.7 X 10(5) adrenaline cells and 1.5-1.9 X 10(5) noradrenaline cells. Chromaffin granules account for approximately 30% of the volume of the cytoplasm; the numerical density of granules at different sites in the cell was calculated for adrenaline cells. The volume density of mitochondria (4%) and the surface density of mitochondrial membranes (the ratio of outer to inner membrane being approximately 1:2.3) were similar in both cell types. Rough endoplasmic reticulum was the only organelle to show a significant difference in volume and surface density between the two cell types. Adrenaline storing cells have stacks of rough endoplasmic reticulum which have two to three times the surface and volume densities of that found diffusely scattered throughout noradrenaline cells. The adrenaline content of an adrenaline storing cell is 0.14 X 10(-6) microM and that of a granule 3.0 X 10(-12) or 3.8 X 10(-12) mumoles depending on the method of calculation. The noradrenaline content of noradrenaline storing cells can only be calculated on the assumption that all noradrenaline is stored in this cell type though it is likely that some is contained within adrenaline cells. Based on this assumption the noradrenaline content is 0.17 X 10(-6) mumoles per cell and 5 X 10(-12) mumoles per granule. The present study provides baseline morphometric data on the rat adrenal medulla at tissue and cellular level correlated with amine levels in adrenaline and noradrenaline storing cells and granules.

Adrenal Medulla↗

Cyanide loss from tissue baths in the presence and absence of tissue.

Loss of cyanide from Krebs-Henseleit solution (KHS) was studied in aerated tissue baths at 38 degrees C in the presence and in the absence of tissue. The rate of cyanide loss was greater from 300-microM than from 30-microM solutions and still greater from 300-microM solutions in the presence of vascular tissue. Initial cyanide loss was much greater from the tissue-containing bath, and the half-time was shorter in the presence of tissue (54 min) than in its absence (98 min) in baths containing the same initial cyanide concentration (300 microM).

Animals↗

Tissue characterization of benign brain tumors: use of NMR-tissue parameters.

To evaluate the potentials of NMR tissue parameters for tissue characterization we investigated 68 patients with benign brain tumors. Tissue parameters were accurately measured by a recently developed interlaced triple sequence. Each individual tumor was characterized by a set of three numbers (relaxation times T1 and T2 and proton density Rho). Different tumors exhibited significant overlaps of the three tissue parameters. Therefore a reliable prediction of the histological diagnosis based on the quantitative analysis of tissue parameters alone was not possible. T2-prolongation correlated well with water content and "regressive changes" in meningiomas and neuromas.

Adenoma↗

Feasibility of tissue magnetic resonance imaging: a pilot study in comparison with tissue Doppler imaging and invasive measurement.

OBJECTIVES: This research was intended to determine the feasibility of tissue magnetic resonance (MR) imaging in comparison with tissue Doppler imaging and its potential implications for the estimation of filling pressure, in comparison with invasive measurement. BACKGROUND: Evaluation of diastolic function using MR imaging is commonly confined to the study of transmitral flow. However, transmitral flow is unreliable for the estimation of left ventricular (LV) filling pressures in hypertrophy and normal systolic function. Normalizing early mitral velocity (E) for the influence of myocardial relaxation by combining E with early diastolic mitral septal tissue velocity (Ea) provides better Doppler estimates of filling pressures. METHODS: Eighteen patients with hypertensive heart disease (LV mass index: 114 +/- 21 g/m(2)), absence of valvular regurgitation, and with normal or mildly reduced systolic function (LV ejection fraction: 57.6 +/- 6.5%) referred for cardiac catheterization, underwent consecutive measurement of mitral flow and septal tissue velocities with phase-contrast MR and Doppler. These data were compared with mean pulmonary capillary wedge pressure (PCWP). RESULTS: There was a strong relation between MR (11.6 +/- 4.3) and Doppler-assessed (12.1 +/- 3.5) E/Ea (95% confidence interval of -1.5 to 0.5) (r = 0.89, p < 0.0001). In addition, E/Ea related strongly to invasively measured PCWP (MR: r = 0.80, p < 0.0001 and Doppler: r = 0.85, p < 0.0001). CONCLUSIONS: Tissue MR imaging is a feasible method to assess Ea. Combining E and Ea allowed similar estimation of filling pressure by MR and Doppler, in good agreement with invasive measurement. The potential confounding effect of valvular regurgitation needs further study.

Blood Flow Velocity↗

Absence of tissue-bound semicarbazide-sensitive amine oxidase activity in carp tissues.

We have previously reported that carp (Cyprinus carpio) tissue mitochondria contain a novel form of monoamine oxidase (MAO), which belongs neither to MAO-A nor to MAO-B of the mammalian enzyme. This conclusion results from the findings that the carp MAO was equally sensitive to a selective MAO-A inhibitor clorgyline and to the MAO-B selective inhibitor l-deprenyl, when tyramine, a substrate for both forms, serotonin or beta-phenylethylamine, a substrate for either A or B-form of mammalian MAO, was used. In the present study, we tried to detect another amine oxidase, termed tissue-bound semicarbazide-sensitive amine oxidase (SSAO), activity in carp tissues. As definition of SSAO was used, such as insensitivity to inhibition of the kynuramine oxidizing activity by an MAO inhibitor pargyline and high sensitivity to the SSAO inhibitor semicarbazide. The results indicated that the oxidizing activity was selectively and almost completely inhibited by 0.1 mM pargyline alone or a combination of 0.1 mM pargyline plus 0.1 mM semicarbazide, but not by 0.1 mM semicarbazide alone. We also tried to detect any SSAO activity by changing experimental conditions, such as lower incubation temperature, higher enzyme protein concentration, a lower substrate concentration and different pH's in the reaction, as the enzyme source. However, still no SSAO activity could be detected in the tissues. These results conclusively indicate that carp tissues so far examined do not contain SSAO activity.

Amine Oxidase (Copper-Containing)↗

Organ positioning in Drosophila requires complex tissue-tissue interactions.

Positioning an organ with respect to other tissues is a complex process necessary for proper anatomical development and organ function. The local environment surrounding an organ can serve both as a substrate for migration and as a source of guidance cues that direct migration. Little is known about the factors guiding Drosophila salivary gland movement or about the contacts the glands establish along their migratory path. Here, we provide a detailed description of the spatial and temporal interactions between the salivary glands and surrounding tissues during embryogenesis. The glands directly contact five other tissues: the visceral mesoderm, gastric caecae, somatic mesoderm, fat body, and central nervous system. Mutational analysis reveals that all of the tissues tested in this study are important for normal salivary gland positioning; proper differentiation of the visceral and somatic mesoderm is necessary for the glands to attain their final correct position. We also provide evidence that the segment-polarity gene, gooseberry (gsb), controls expression of signals from the developing fat body that direct posterior migration of the glands. These data further the understanding of how organ morphology and position are determined by three-dimensional constraints and guidance cues provided by neighboring tissues.

Animals↗

Extraction of testicular sperm from previously cryopreserved tissue in couples with or without transport of oocytes and testicular tissue.

OBJECTIVE: To evaluate results of IVF and intracytoplasmic sperm injection (ICSI) with extraction of sperm from frozen-thawed testicular tissue. DESIGN: Retrospective follow-up study. SETTING: Fertility center. PATIENT(S): Thirty-five couples with transport of testicular tissue from a transport clinic and 125 local couples. INTERVENTION(S): Extraction of testicular sperm by maceration and enzymatic digestion from frozen-thawed testicular tissue before ICSI. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (PR) and implantation rate in couples with obstructive or nonobstructive azoospermia, motile or immotile sperm, and differing male serum FSH values. RESULT(S): The clinical PR per ET and implantation rate per embryo in couples with transport of testicular tissue were 40% and 18%, respectively, in cases of obstructive azoospermia and 37% and 26%, respectively, in cases of nonobstructive azoospermia. In the local couples, these rates were 42% and 19%, respectively, in cases of obstructive azoospermia and 18% and 10%, respectively, in cases of nonobstructive azoospermia. The implantation rates for ICSI were 26% with motile sperm and 11% with immotile sperm in the transport group and 16% and 8%, respectively, in the local group. Male serum FSH level did not clearly correlate with implantation rate. CONCLUSION(S): Clinical PR and implantation rate are not affected by transport of testicular tissue but are significantly affected by nonobstructive azoospermia and the use of immotile sperm. No major increase in chromosomal aberration or congenital malformation was noted in the offspring of this limited group.

Adolescent↗

Detection of t(11;18)(q21;q21) in marginal zone lymphoma of mucosa-associated lymphocytic tissue type on paraffin-embedded tissue sections by using fluorescence in situ hybridization.

A chromosomal t(11;18)(q21;q21) recurrently found in marginal zone lymphomas of mucosa-associated lymphocytic tissue (MALT) type is one of the key determinants of their treatment and outcome because t(11;18)-positive cases are resistant to Helicobacter pylori eradication therapy. To detect t(11;18) on paraffin-embedded tissue sections, we established a method of dual-color fluorescence in situ hybridization (D-FISH) using DNA probes directly labeled with SpectrumGreen and SpectrumOrange (tissue-FISH [T-FISH]). T-FISH detected the t(11;18) as colocalized signals between the band-specific yeast artificial chromosome (YAC) clones y966e4 (11q21) and y943b8 (18q21) on the der(11)t(11;18). The t(11;18) was detected in four of 22 patients with marginal zone lymphoma of MALT type in 72%-78% of the cells. In both patients studied, the percentage of t(11;18)-positive cells was much higher in tissue-FISH analysis than in interphase-FISH: 74% versus 30% in patient 1 and 75% versus 31% in patient 4. None of the 12 patients with diffuse large B-cell lymphoma of the stomach showed the t(11;18). Tissue-FISH is a powerful tool for the diagnosis of marginal zone lymphoma of MALT type because it can be applied not only to small specimens obtained from endoscopic biopsy samples but also to archival materials, hence facilitating the delineation of subtypes in marginal zone lymphoma of MALT type.

Adult↗