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Results for “tissue heterogeneity”

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At least 19 recordsLinked to original sources
PubMed1992

Errors introduced by tissue heterogeneity in estimation of local cerebral glucose utilization with current kinetic models of the [18F]fluorodeoxyglucose method.

The effects of tissue heterogeneity on the estimation of regional cerebral glucose utilization (rCMRglc) in normal humans with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) were compared with respect to the various kinetic models of the [18F]FDG method. The kinetic models were conventional homogeneous tissue models of the [18F]FDG method, with (4K Model) and without (3K Model) a rate constant to account for an apparent loss of [18F]2-fluoro-2-deoxy-D-glucose-6-phosphate ([18F]FDG-6-P), and a tissue heterogeneity model (TH Model). When either of the kinetic models designed for homogeneous tissues was applied to heterogeneous tissues, estimates of the rate constant for efflux of [18F]FDG from the tissue (k2*) and of the rate constant for phosphorylation of [18F]FDG (k3*) decreased as the duration of the experimental period was increased. When the 4K Model was used, estimates of the rate constant for the apparent dephosphorylation of [18F]FDG-6-P (k4*) were significantly greater than zero and fell with increasing duration of the experimental period. Although the TH Model included no term to describe an apparent dephosphorylation of [18F]FDG-6-P, the fit of the TH Model to the time course of total tissue radioactivity was at least as good as and often better than the fit of the 4K Model in the 120-min period following the pulse of [18F]FDG. Hence, the high estimates of k4* found in PET studies of less than or equal to 120 min can be explained as the consequence of measuring radioactivity in a heterogeneous tissue and applying a model designed for a homogeneous tissue; there remains no evidence of significant dephosphorylation of [18F]FDG-6-P in this time period. Furthermore, use of the 4K Model led to an overestimation of rCMRglc; whole-brain glucose utilization calculated with the 4K Model was greater than 20% higher than values usually obtained in normal humans by the model-independent Kety-Schmidt technique. rCMRglc was accurately estimated by the TH Model and, in experimental periods sufficiently long to minimize the effects of tissue heterogeneity, also by the original 3K Model of the deoxyglucose method.

Adult↗
PubMed1992

Low oxygen extraction fraction in tumours measured with the oxygen-15 steady state technique: effect of tissue heterogeneity.

Several reports have described decreased oxygen extraction fractions in tumours relative to those in normal tissues as measured with the oxygen-15 steady state technique and positron emission tomography. The present simulation study was carried out to assess the influence of tissue heterogeneity on these measured values. It was found that, within the range analyzed, tissue heterogeneity always resulted in underestimations of mean values of oxygen extraction fraction. It must, therefore, be concluded that the oxygen-15 steady state technique is not an accurate method for the assessment of the oxygen status of tumours. This finding should also apply to other pathological conditions, where a significant degree of tissue heterogeneity can not be excluded. More generally, this study demonstrates the need for detailed analyses of sensitivities of tracer kinetic procedures to tissue heterogeneity.

Brain Neoplasms↗
PubMed2026

Accurately Deciphering Tissue Heterogeneity From Spatial Multi-Modal and Multi-Omics With STransformer.

Advances in spatially resolved technologies enable the simultaneous acquisition of diverse data modalities within a tissue slice while preserving critical spatial context, which presents unprecedented opportunities to decipher intricate tissue heterogeneity. However, existing computational approaches lack the intrinsic flexibility to universally process both spatial multi-modal and multi-omics data. Here, we introduce STransformer, a unified deep learning framework designed to seamlessly accommodate a comprehensive landscape of spatial data. By simultaneously capturing short-range cellular interactions and tissue-wide semantic patterns, it extracts robust representations to accurately dissect complex tissue heterogeneity. Systematic evaluations across diverse species, tissue types, and data modalities highlight its profound versatility. For spatial multi-modal data, STransformer delineates intricate anatomical structures in the human cortex, uncovers pathological mechanisms in Alzheimer's disease, and characterizes dynamic spatiotemporal developmental trajectories during chicken cardiogenesis. Scaling to spatial multi-omics data, STransformer synergizes spatial transcriptomic and proteomic profiles to decipher intricate immune microenvironments within the human tonsil, and jointly analyzes spatial epigenomic and transcriptomic data to infer regulatory mechanisms in the mouse embryonic brain. Consequently, STransformer serves as a highly versatile and robust analytical framework for advancing our understanding of tissue heterogeneity and disease pathogenesis.

Multiomics↗
PubMed1976

Tissue heterogeneity in the anterior chest wall and its influence on radiation therapy of the internal mammary lymph nodes.

The density (g cm-3) and electron density (cm-3) of material from the anterior chest wall was determined. On the average, the difference in density between rib bone and intercostal soft tissue amounted to 17 per cent, while the difference in electron density was 7 per cent. The attenuation of high-energy electrons in specimens of rib bone, costal cartilage and sternum was determined by an experimental technique, using dosimeters of TLD material. The results of determinations of attenuation of 10 and 13 MeV electrons in fresh specimens are presented. It is concluded that electron radiation in the energy range of 10 to 13 MeV can be utilized for irradiation of lymph glands along the internal thoracic vessels without risk of underdosage.

Adipose Tissue↗
PubMed1978

Molecular and tissue-specific heterogeneity in HPRT deficiency.

In several patients with different degrees of HPRT deficiencies, residual activities have been determined in both lysed and intact erythrocytes. No close correlation could be found between the degree of HPRT deficiency and the severity of the clinical expression. Unless HPRT activity in both intact and lysed erythrocytes was below detection level, the residual activity in intact red blood cells was higher than in lysates. Tissue-specific heterogeneity was illustrated with a patient suffering from X-linked gout. Lysates from erythrocytes, leukocytes, and cultured fibroblasts showed 1%, 8%, and 100% of normal HPRT activity, respectively. Characterization of the erythrocyte and fibroblast HPRT from this patient showed no kinetic abnormalities. However, there was a decreased heat stability. It is concluded that for a better understanding of the pathophysiology in HPRT deficiency studies on nucleated cells from the different tissues are needed.

Erythrocytes↗
PubMed1992

Molecular characterization of areas with low grade tumor or satellitosis in human malignant astrocytomas.

Malignant astrocytomas often display histopathological heterogeneity. In the present study, we have molecularly characterized different areas within 4 such tumors to determine whether the tissue heterogeneity can be explained by differences in DNA constitution. Two tumors contained low grade areas, and the other 2 had areas with satellitosis. The tumors were examined for loss of heterozygosity with markers from chromosomes 9p, 10, and 17p and for amplification of the epidermal growth factor receptor gene. In each case, the high grade portion of the tumor displayed at least one of these structural alterations. However, identical alterations were found in the associated low grade or satellitosis areas of each tumor. Our data suggest that: (a) genetic alterations associated with tumor progression already occur in histopathologically low grade areas of high grade astrocytoma; (b) satellitosis associated with a high grade astrocytoma has to be considered as part of that tumor; and (c) tissue heterogeneity within a high grade astrocytoma is not a consequence of differences in DNA constitution at the loci that were examined.

Astrocytoma↗
PubMed2025

Polygenic enrichment analysis in multi-omics levels identifies cell/tissue specific associations with schizophrenia based on single-cell RNA sequencing data.

OBJECTIVE: Understanding the specific cellular origin and tissue heterogeneity in schizophrenia is critically important for exploring the disease etiology. This study aims to investigate these aspects by performing multiple analyses based on omics data. METHOD: We performed single-cell disease relevance score (scDRS) algorithm to link brain single-cell RNA sequencing (scRNA-seq) with schizophrenia risk across multi-omics scales at single-cell resolution. This approach identified cell types with overexpression of schizophrenia-related genes implicated by multi-omics panels (ATAC-seq, RNA-seq, TWAS, and GWAS). Schizophrenia-related genes from these multi-omics panels were extracted and combined with scRNA-seq data to calculate scDRS. Subsequently, the cell-type vs. disease association and tissue heterogeneity were assessed using scDRS for each omics panel. RESULTS: We identified two novel cell subpopulations in the brain that differentially express SCUBE3 (59 cells, 7.0 %) and FN1 (21 cells, 2.5 %). At the individual cell level, schizophrenia-associated cell subpopulations included microglial cell associated with ATAC-seq panel (Passociation = 0.002, Pheterogeneity = 0.009) and deep layer neuron suggestively associated with GWAS panel (Passociation = 0.033, Pheterogeneity = 0.017). At the brain tissue level, microglial cell was significantly associated with cortical plate in ATAC-seq panel (Passociation = 0.002, Pheterogeneity = 0.011). Gene level analysis identified several genes associated with schizophrenia across multi-omics panels. CONCLUSIONS: Our study outlines the signature of cell subpopulations, brain regions, and disease risk genes in schizophrenia at single-cell resolution across multi-omics scales. These findings provide a reference for future precision medicine approaches targeting specific cell types and brain regions in schizophrenia.

Schizophrenia↗
PubMed1976

The keratin chains of avian scale tissue. Sequence heterogeneity and the number of scale keratin genes.

The three major proteins of chick scale keratin were isolated as their S-carboxymethylated derivatives and shown to be similar or identical in molecular weight by gel filtration but to be distinct by amino acid analysis and gel electrophoresis. The major amino-terminal sequence of scale keratin chains was determined and shown to be highly homologous to the corresponding region of feather keratin chains. The carboxyl-terminal peptides of the three scale keratin fractions differed in sequence but were all homologous to the carboxyl-terminal segment of feather keratin chains. The pronounced concentration of cysteine residues at the amino-terminal and carboxyl-terminal segments suggested a similar role for these regions in both scale and feather keratin chains, namely to provide a disulphide-linked matrix to maintain the organisation of fibrils which arise from the internal hydrophobic segments of both types of chain. Analysis of a large hydrophobic segment from each of the three isolated protein fractions revealed that each was composed largely of repeating tripeptide units of the type Gly-Gly-X (where X = Phe, Leu or Tyr). At a few positions in each hydrophobic peptide, microheterogeneity was apparent in the sequences indicating that each isolated protein fraction was composed of at least three different chains each encoded by a different gene. A minimum of nine keratin genes are therefore expressed in scale tissue.

Amino Acid Sequence↗
PubMed1979

Studies on the nuclear binding of steroid hormone-receptor complex; binding of liver and thymus dexamethasone-receptor complex and prostate dihydrotestosterone-receptor complex to nuclei from various tissues.

To examine the binding specificity of steroid hormone-cytoplasmic receptor complexes to nuclei, binding of 3H-dexamethasone (Dex)-liver, 3H-Dex-thymus and 3H-dihydrotestosterone (DHT)-prostate receptor complexes to nuclei from liver, prostate, thymus, spleen and kidney was studied. It was observed that a significant amount of steroid-receptor complexes was bound to any nuclei used in the present study and the extent of the binding of receptor complexes to nuclei from homologous tissues was not always greater than that to nuclei from heterogenous tissues. However, a significant portion of the 3H-Dex-liver and 3H-DHT-prostate receptor complexes was not absorbed by nuclei from kidney, spleem, and thymus, and the unabsorbed complexes were efficiently bound to liver and prostate nuclei. The results obtained indicate that two types of receptor complex with regard to nuclear binding were present in cytosols of liver and prostate; one binds to nuclei from kidney, spleen, thymus, liver and prostate and the other does not bind to nuclei from kidney, spleen and thymus but does bind to nuclei of liver and prostate. The latter type of receptor complex was not observed in the cytosol from the thymus.

Animals↗
PubMedDate not supplied

Macroscopic geometric heterogeneity effects in radiation dose distribution analysis for boron neutron capture therapy.

Calculations of radiation flux and dose distributions for boron neutron capture therapy (BNCT) of brain tumors are typically performed using sophisticated three-dimensional analytical models based on either a homogeneous approximation or a simplified few-region approximation to the actual highly heterogeneous geometry of the irradiation volume. Such models should be validated by comparison with calculations using detailed models in which all significant macroscopic tissue heterogeneities and geometric structures are explicitly represented as faithfully as possible. This paper describes such a validation exercise for BNCT of canine brain tumors. Geometric measurements of the canine anatomical structures of interest for this work were performed by dissecting and examining two essentially identical Labrador retriever heads. Chemical analyses of various tissue samples taken during the dissections were conducted to obtain measurements of elemental compositions for the tissues of interest. The resulting geometry and tissue composition data were then used to construct a detailed heterogeneous calculational model of the Labrador head. Calculations of three-dimensional radiation flux distributions pertinent to BNCT were performed for this model using the TORT discrete-ordinates radiation transport code. The calculations were repeated for a corresponding volume-weighted homogeneous-tissue model. Comparison of the results showed that peak neutron and photon flux magnitudes were quite similar for the two models (within 5%), but that the spatial flux profiles were shifted in the heterogeneous model such that the fluxes in some locations away from the peak differed from the corresponding fluxes in the homogeneous model by as much as 10%-20%. Differences of this magnitude can be therapeutically significant, emphasizing the need for proper validation of simplified treatment planning models.

Animals↗
PubMed1975

Cyclic AMP and cyclic GMP: studies utilizing immunohistochemical techniques for the localization of the nucleotides in tissue.

Antibodies to the cyclic nucleotides initially were utilized in radioimmunoassays for cyclic AMP and cyclic GMP which might be present in mammalian tissues. allowed measurement of the nucleotides on small amounts of tissue in physiologic studies. To gain further insight into the relative roles of cyclic AMP and cyclic GMP in cell function, these antibodies have been applied to immunohistochemical studies for the localization of the cyclic nucleotides in tissues and cells. This methodology is useful for determining in which cell type in a heterogeneous tissue increases in cyclic nucleotide concentrations occur. In addition, within individual cells, staining patterns for cyclic AMP and cyclic GMP are usually quite distinct. Cyclic GMP in canine thyroid is located to the follicular cell membrane while cyclic AMP is ubiquitously distributed in follicular cell cytoplasm. In both rat adrenal cortex and testis, there is prominent nuclear localization of cyclic GMP, suggesting a role for the nucleotide in growth regulation. These studies provide histologic evidence suggesting diverse roles for cyclic AMP and cyclic GMP in mammalian physiology. It is anticipated that this technique will also be useful in the ultrastructural localization of the cyclic nucleotides and for the identification of other cyclic nucleotides which might be present in mammalian tissues.

Adrenal Glands↗
PubMed1977

Radiotherapy treatment planning using the ACTA-scanner.

Computerized tomography is useful in radiotherapy treatment planning in the following ways: (1) Its image provides the most accurate possible contour of the patient and demonstrates the internal structures in their proper relation to each other. (2) The tumor and its extension are accurately demonstrated. (3) Corrections for tissue heterogeneities can be accomplished in one of two ways, either by arbitrary assignment of densities to tissues or by direct scanning with a therapy source. This latter procedure is under investigation. (4) The computer can be programmed to demonstrate summations of dose delivered from multiple fields.

Dose-Response Relationship, Radiation↗
PubMed1992

Tissue distribution of human minor histocompatibility antigens. Ubiquitous versus restricted tissue distribution indicates heterogeneity among human cytotoxic T lymphocyte-defined non-MHC antigens.

We determined the tissue distribution of 7 human minor histocompatibility (H) Ag. Each of these Ag is defined by one or more MHC class I-restricted CTL clones, previously generated from PBL primed against minor H Ag by HLA-identical bone marrow transplantation (BMT). CTL-mediated lysis of tissue-derived cells and cultured cell lines was used as an in vitro assay for minor H Ag expression of several human tissues. The Ag HA-3 (HLA-A1-restricted), HA-4 (HLA-A2 restricted), HA-6 and HA-7 (HLA-B7 restricted), and the male-specific Ag H-Y (HLA-A2 and B7 restricted) were found to be expressed on cells of all tissues tested. In contrast, the HLA-A2-restricted Ag HA-1 and HA-2 were demonstrated on PHA-blasts, EBV-BLCL, purified T cells, B cells, monocytes, and immature thymocytes, but could not be demonstrated on skin-derived cultured fibroblasts, keratinocytes, melanocytes, cultured epithelial cells of kidney proximal tubili, and umbilical cord vein-derived endothelial cells. Incubation of the latter cell lines with rIFN-gamma, rTNF-alpha, and/or rIL-1 alpha, in concentrations shown to maximally increase their susceptibility to lysis by allo-MHC class I CTL, did not induce recognition by HA-1- and HA-2-specific CTL in vitro. These results indicate an ubiquitous tissue expression of the minor H Ag HA-3, -4, -6, -7 and H-Y in contrast to a to the hemopoietic cell lineage-restricted expression for HA-1 and HA-2. The heterogeneity in tissue expression of T cell-defined, class I-restricted non-MHC Ag implies that they might be derived from intracellular proteins with either an ubiquitous or a more specialized cell type-specific function.

Cytotoxicity, Immunologic↗
PubMed1975

Explorotory study of proton radiation therapy using large field techniques and fractionated dose schedules.

Three patients have been treated with 160-MeV protons combined with high-energy photons to examine the advantages and difficulties associated with the clinical implementation of a program of large-field, fractionated-dose, protonradiation therapy. We havefound it necessary to 1) obtain an accurate three-dimensional determination of the treatment volume including the density of all tissues in the beam path; 2) construct an adequate bolus to compensate for tissue heterogeneities; 3) use much more precise and accurate immobilization and patient positioning devices than used in photon irradiation; 4) treat with both protons and photons so as to keep the skin dose within an acceptable level. IN TISSUES WITHOUT SIGNIFICANT INHOMOGENETIES DUE TO BONE AND AIR SPACES WE HAVE DELIVEREDA WELL-DEFINED DOSE TO INVOLVED TISSUES WHILE SPARING DISTAL SENSITIVE STRUCTURES. However, in those regions where there is much "fine structure" of tissue density, it has been difficult to compensate satisfactorily for the inhomogeneties.

Adult↗
PubMed1977

Immunohistochemical localization of 3':5'-cyclic AMP and 3':5'-cyclic GMP in rat renal cortex: effect of parathyroid hormone.

Adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP) were localized in cells of rat kidney cortex by an immunocytochemical technique before and after perfusion with parathyroid hormone (PTH). In control tissues the cAMP antiserum detected approximately the same intensity of fluorescence in cytoplasmic epithelial cell elements of cortical tubules and glomeruli (cells of Bowman's capsule and podocytes). PTH increased fluorescence in these glomerular cells and increased cAMP fluorescence in cytoplasmic granules in proximal tubular cells. These granules, whose structure has not been identified, were located predominantly on the luminal side of the tubular cells. In control rats, the renal cortical fluorescence detected with the cGMP antiserum was more pronounced in glomeruli (predominantly in the mesangial areas) and lesser amounts of fluorescence were observed in tubules. After PTH treatment, cGMP fluorescence increased in glomeruli and in renal tubular cells. A bright linear pattern of fluorescence was found in the area of the tubular luminal membrane. Perfusion with PTH caused relatively small increases in total tissue cAMP and no consistent increases in total tissue cGMP. Our observations suggest that both cAMP and cGMP are involved in the glomerular and tubular responses to PTH and point out the added dimension that this immunocytochemical technique brings to studies of cyclic nucleotide dynamics in heterogeneous tissues.

Animals↗