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Results for “Tissue Array Analysis”

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At least 19 recordsLinked to original sources

PubMed2026

Profiling Dectin-2-Positive Tumor-Associated Macrophages Across Human Cancers by Immunohistochemistry.

PURPOSE: To characterize the prevalence and distribution of Dectin-2-positive macrophages across human tumors and develop a research immunohistochemistry (IHC) assay to assess Dectin-2 in cancer tissues. MATERIALS AND METHODS: C-type lectin domain family 6 member A (CLEC6A), the gene encoding Dectin-2, was evaluated across 38 tumor types using The Cancer Genome Atlas. A fit-for-purpose Dectin-2 IHC assay was developed using a monoclonal antibody selected from screening 11 anti-Dectin-2 antibodies. Assay performance was supported by Dectin-2-expressing and parental cell line controls, macrophage-associated staining patterns, and comparison with an orthogonal CLEC6A in situ hybridization method using RNAscope. Dectin-2 expression was assessed in tissue microarrays (n = 553 samples) across 6 cancer types and whole tissue sections (n = 137) across 7 cancer types. RESULTS: The Cancer Genome Atlas analysis identified enriched CLEC6A expression in several tumor types, including non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), and subsets of head and neck cancer (HNC) and colorectal cancer (CRC). By IHC, Dectin-2-positive macrophages were detected across tumor types, with notable heterogeneity within and across cancer types. In tissue microarrays, NSCLC showed the highest frequency of Dectin-2-positive macrophage infiltration, with 38% of cases with staining ≥1% of tumor area. Whole tissue section analysis confirmed and expanded these findings, with ≥50% of NSCLC, melanoma, HNC, TNBC, and CRC samples showing Dectin-2-positive macrophages in ≥1% tumor area. CONCLUSIONS: Dectin-2 expression was observed in subsets of tumor-associated macrophages across multiple human cancers, with relatively enriched expression in NSCLC, melanoma, HNC, TNBC, and CRC. To our knowledge, this study represents the first broad protein-level characterization of Dectin-2 across multiple human tumor types, identifies cancers with relatively enriched Dectin-2-positive macrophage infiltration, and provides a foundation for future translational studies of Dectin-2-targeted therapies.

Humans↗

PubMed2026

Integrated expression profiling of trophoblast cell-surface antigen 2 (TROP2), folate receptor alpha (FRα), and human epidermal growth factor receptor 2 (HER2) in endometrial Cancer across molecular classes, genomic alterations, and histologic subtypes.

OBJECTIVE: Antibody-drug conjugates (ADCs) are expanding treatment options in endometrial carcinoma, but the distribution of actionable surface targets across histologic, molecular, and genomic subgroups remains incompletely defined. METHODS: This single-institution retrospective tissue microarray (TMA) study included 312 endometrial carcinomas: 158 endometrioid and 154 serous tumors. Trophoblast cell-surface antigen 2 (TROP2) was quantified by histochemical score (H-score); human epidermal growth factor receptor 2 (HER2) was assessed using endometrial carcinoma-specific and gastric/DESTINY-PanTumor02 criteria; and folate receptor alpha (FRα) positivity was defined as ≥75% viable tumor cells with ≥2+ membranous staining. Molecular class was assigned using a hierarchical DNA polymerase epsilon (POLE)-mutant, microsatellite instability/mismatch repair-deficient (MSI/MMRd), p53-abnormal, and no specific molecular profile (NSMP) classifier. Tumor mutational burden (TMB) and recurrent genomic alterations were analyzed in relation to biomarker expression. RESULTS: TROP2 was broadly expressed, with median H-scores of 280 in endometrioid and 200 in serous carcinomas. HER2 gastric-score 2+/3+ expression and FRα positivity were enriched in serous versus endometrioid carcinoma (22.5% vs 8.9% and 20.1% vs 4.4%), restricted to FIGO grade 3 tumors, and concentrated in p53-abnormal disease. FRα positivity was absent in POLE-mutant and MSI/MMRd tumors. HER2 2+/3+ expression correlated with erb-b2 receptor tyrosine kinase 2 (ERBB2) alterations, whereas FRα-positive tumors were enriched for TP53 alterations and showed lower frequencies of ARID1A and PTEN alterations. Triple-negative TROP2/HER2/FRα tumors were uncommon (6/308, 1.9%). CONCLUSIONS: TROP2 is broadly expressed in endometrial carcinoma, whereas HER2 and FRα define a more restricted high-grade, serous/serous-like, p53-abnormal compartment, supporting biomarker-informed ADC development.

Humans↗

PubMed2026

Profiling tumor immune microenvironment of epithelial ovarian carcinoma.

BACKGROUND: Epithelial ovarian carcinoma (EOC) comprises five main histological subtypes: high-grade serous (HGSOC), low-grade serous (LGSOC), clear cell (CCOC), mucinous (MOC), and endometrioid (ENOC). Each histotype harbors specific genomic alterations and clinical outcome. Few studies systematically compared the tumor immune microenvironment across the five subtypes. METHODS: We performed 7-plex (CD45, CD8, CD68, CD163, FoxP3, CD20, and cytokeratin) sequential immunohistochemistry on a clinically annotated tissue microarray including 139 EOC representing the five subtypes and 26 borderline tumors (serous and mucinous). Digital pathology was used to quantify immune cell abundance, their spatial distribution (stroma vs tumor core), and correlation with survival. RESULTS: Immune cells were dominated by macrophages and more abundant in the stroma than tumor core across the five subtypes, consistent with immune excluded pattern. Compared to HGSOC, CCOC displayed the highest infiltration by CD45+ leukocytes and CD68+ macrophages, particularly M2-like CD163+ cells, suggesting a macrophage-rich, immunosuppressive phenotype. LGSOC exhibited the highest infiltration by intraepithelial FoxP3+ regulatory T cells. Comparison of borderline tumors with invasive carcinoma (LGOSC and MOC) revealed that malignant progression is accompanied by loss of CD8+ T cells, enrichment in regulatory T cells and increase of CD163+/CD68+ ratio, consistent with immune evasion during tumorigenesis. There was a trend toward better survival in HGSOC highly infiltrated by lymphocytes, either intraepithelial (CD8+ and FoxP3+) or stromal (FoxP3+ and CD20+). CONCLUSIONS: EOC is characterized by histotype-specific immune milieux defined by macrophage dominance, epithelial immune exclusion and dynamic immune remodeling during progression from borderline tumors to invasive carcinomas.

Humans↗

PubMed1988

Mesangial IgA in IgA nephropathy arises from the mucosa.

Numerous studies have attempted to elucidate the pathogenetic mechanisms of IgA nephropathy, analyzing kidney, serum, lymphocytes, and lymphoid tissue of patients with this glomerulonephritis. Based on studies of the molecular characteristics of the mesangial IgA, clinical features, and immunologic analysis of the mucosal tissue, a wide array of findings suggest that mesangial IgA indeed arises from the mucosa. These three areas of research are discussed, as well as the hypothesis of a systemic origin for the mesangial IgA.

Glomerular Mesangium↗

PubMed1992

Hybridization fingerprinting of high-density cDNA-library arrays with cDNA pools derived from whole tissues.

As part of an integrated mapping and sequencing analysis of genomes, we have developed an approach allowing the characterization of large numbers of cDNA library clones with a minimal number of experiments. Three basic elements used in the analysis of cDNA libraries are responsible for the high efficiency of this new approach: (1) high-density library arrays allowing thousands of clones to be screened simultaneously; (2) hybridization fingerprinting techniques to identify clones abundantly expressed in specific tissues (by hybridizations with labeled tissue cDNA pools) and to avoid the repeated selection of identical clones and of clones containing noncoding inserts; and (3) a computerized system for the evaluation of hybridization data. To demonstrate the feasibility of this approach, we hybridized high-density cDNA library arrays of human fetal brain and embryonal Drosophila with radiolabeled cDNA pools derived from whole mouse tissues. Fingerprints of the library arrays were generated, localizing clones containing cDNA sequences from mRNAs expressed at middle to high abundance (> 0.1-0.15%) in the respective tissue. Partial sequencing data from a number of clones abundantly expressed in several tissues were generated to demonstrate the value of the approach, especially for the selection of cDNA clones for the analyses of genomes based on expressed sequence tagged sites. Data obtained by the technique described will ultimately be correlated with additional transcriptional and sequence information for the same library clones and with genomic mapping information in a relational database.

Animals↗

PubMed1991

Cepstral analysis of ultrasound in chronic liver disease--a preliminary study in the non-invasive evaluation of structural change.

To evaluate the morphological changes in chronic liver disease non-invasively we used the frequency-domain analysis of ultrasound. We assumed that liver tissue is a collection of semi-regularly arrayed small scatterers of ultrasound. We applied cepstral analysis to ultrasonic waveforms and evaluated the periodicity of scalloping of the power spectrum, caused by an interference effect among liver scatterers of a given spacing. In a phantom experiment, we could correctly measure the space among scatterers of a phantom consisting of a regularly spaced distribution of nylon filaments. In an experiment involving a freshly excised porcine liver, the distribution of the space among scatterers (SAS) determined on cepstral analysis reflected the size distribution of the hepatic lobules. In a human study, two statistical parameters, mode and kurtosis, were determined from the distribution of the SAS for each patient. In a previous study, we collected ultrasonic data during peritoneoscopy with a 10 MHz transducer directly contacting the liver and showed that we could evaluate morphological changes in chronic liver disease using cepstral analysis. In the present study, we obtained data in two ways: with a 3.5 MHz transducer through the abdominal wall and with a 10 MHz transducer directly contacting the liver during peritoneoscopy. The mode and kurtosis of the SAS obtained with the 3.5 MHz transducer were both well correlated with the mode and kurtosis of the SAS obtained with the 10 MHz transducer. These results suggest that we can evaluate morphological changes in chronic liver disease non-invasively.

Animals↗

PubMed1989

Fully automated measurements by light microscopy of tissue sections using a cellular array computer.

Software was developed for the acquisition, segmentation and analysis of microscopic OD-images on a VICOM digital image processor, extended with a VISIOMORPH morphoprocessor board. The delineation algorithms for peroxisomes, lysosomes, and nuclei in liver, kidney, and adrenal gland sections start by thresholding the difference between the original image and a low pass filtered version. The resulting binary mask is then processed by morphological operations in order to produce an object overlay. The efficiency of the programs is evaluated by comparing delineated objects at different OD-levels, created by varying the stain or by multiplying the original pixel values with constant factors. Manual delineation on some images is also used as a reference. More complex algorithms are used for the delineation of muscle fibres in ATP-ase-stained sections and immunocytochemically labelled cells in monolayer preparations. Muscle images from parallel sections with different stainings are matched with a coordinate transform, enabling the transfer of the object mask from a single delineated image to the unprocessed images and thus obtain all necessary information for fibre classification. After segmentation, the OD-images and their object overlays are fed into a data extraction program, measuring for each delineated object user-selected features. Data are sent to a VAX for statistical interpretation.

Adrenal Cortex↗

PubMed2026

Temporal Transcriptomic Profiling of NMBA-Induced Rat Esophageal Squamous Carcinogenesis Identifies Early Inflammatory Activation and Late NRF2-Associated Oxidative-Stress Remodeling.

Temporal molecular events during early esophageal squamous carcinogenesis remain incompletely defined, in part because human precursor tissues are difficult to obtain sequentially. We used the N-nitrosomethylbenzylamine (NMBA)-induced rat model to characterize stage-associated transcriptional programs during esophageal squamous carcinogenesis. Vehicle-control reference esophageal tissues and NMBA-treated esophageal tissues, collected at weeks 6 and 29, were profiled using Affymetrix Rat Genome 230 2.0 arrays, followed by pathway analysis and qRT-PCR validation of selected genes. Relative to vehicle-control reference tissues, 173 genes were differentially expressed at week 6, whereas 1628 genes were differentially expressed at week 29, indicating marked expansion of transcriptional dysregulation during carcinogenic progression. Sixteen genes were differentially expressed only at week 6, while 157 genes were altered at both time points. Pathway analysis suggested that inflammatory and immunologic processes were prominent during the early response to NMBA exposure, whereas late-stage carcinogenesis was characterized by NRF2-associated oxidative-stress response and dysregulation of multiple glutathione S-transferase family members. A subset of progression-associated genes, including Defb4, Gsta2, Sbsn, Spink5, Plcd4, Hbb, and Hba-a2, showed increasing dysregulation from week 6 to week 29. These findings define temporally distinct molecular programs in NMBA-induced esophageal squamous carcinogenesis and provide a framework for prioritizing candidate pathways and genes relevant to esophageal cancer prevention, early detection, and progression biology.

Animals↗

PubMed1992

Regulation of insulin-like growth factor-binding proteins in the baboon (Papio anubis) uterus during early pregnancy.

The baboon uterus begins to synthesize insulin-like growth factor-binding protein-1 (IGFBP-1) in the deep glands of the late secretory endometrium, and this protein then becomes the major secretory product of the term decidua. We hypothesized that the placenta and/or conceptus may regulate the synthesis and secretion of IGFBP-1 by decidualized stromal cells during pregnancy. To test this hypothesis, tissue was obtained from pregnant baboons on days 18, 25, and 32 postovulation. The uterus was separated into three regions: RI (directly below the implantation site), RII (adjacent to the implantation site), and RIII (opposite the implantation site). Portions of the tissue were fixed in Bouin's solution for immunocytochemistry, and the remainder was subdivided into functionalis, basalis, and myometrium and subjected to organ explant culture. The placenta was fixed or cultured separately. Ligand blot analysis of functionalis medium showed that the major IGFBP had a mol wt (Mr) of 29,000-31,000; however, a doublet of 37,000-43,000 Mr and a band at 24,000 Mr were also present. The functionalis from all regions expressed the majority of the IGFBPs, but basalis from RI tissue also secreted the same array of IGFBPs on days 25 and 32. Ligand blot analysis of placental medium proteins revealed a doublet at Mr 37,000-43,000 on days 25 and 32, but not on day 18. Immunoprecipitation followed by ligand blot analysis of medium proteins using polyclonal antibodies to IGFBP-1 and IGFBP-2 and -3 confirmed that IGFBP-1 and -2 were the predominant products of the endometrium and decidua, while IGFBP-3 was synthesized by the placenta. Immunocytochemistry with a monoclonal antibody to IGFBP-1 demonstrated intense glandular epithelial staining in all regions on days 18, 25, and 32. Stromal staining for IGFBP-1 was first evident on day 25 and was only present in stromal cells in intimate contact with the trophoblastic tissue. By day 32, IGFBP-1 expression was not limited to the endometrial-trophoblastic junction, but extended to the deeper stromal cells and included the perivascular regions. IGFBP-1 staining was most intense in RI, but stromal cells at the luminal surface and those surrounding the spiral arteries also showed some staining in RII and RIII on day 32. These studies suggest that the baboon placenta and/or conceptus regulate IGFBP expression in the uterine endometrium during the initial stages of pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Detection of Aeromonas salmonicida from fish by using polymerase chain reaction amplification of the virulence surface array protein gene.

A DNA-based assay was developed to detect Aeromonas salmonicida from infected fish by analyzing tissues, feces, and the tank water in which the infected fish were held. This analysis was done both by direct detection from samples and after a bacterial outgrowth step. Polymerase chain reaction (PCR) amplification of a 421-bp sequence from the 3' region of the surface array protein gene (vapA) of A. salmonicida provided a specific and sensitive method for the detection and identification of this important fish pathogen. The sensitivity of PCR detection of A. salmonicida directly from tissues was less than 10 CFU/mg. Furthermore, a detection level of 5 fg, equivalent to approximately 1 cell, was obtained by using purified chromosomal DNA as the template. This highly reproducible assay, which requires 45 min to complete, is therefore sensitive enough to be used as a noninvasive method for monitoring fish populations for the presence of carrier fish. Because the surface protein array (A-layer) is a virulence factor of A. salmonicida, PCR analysis with oligonucleotide primers directed at vapA can also be used to provide information on the potential virulence of a strain.

Aeromonas↗

PubMed1991

Ultrasonic tissue characterization of chronic liver disease using cepstral analysis.

To evaluate the morphological changes in chronic liver disease by means of ultrasonography, cepstral analysis was applied to the ultrasonic waveforms obtained with a 10-MHz transducer during peritoneoscopy. Assuming that liver tissue was a collection of semiregularly arrayed small scatters of ultrasound, the spaces between scatterers of the liver could be measured by means of cepstral analysis. From the distribution of the spaces between scatterers, two statistical parameters, mode and kurtosis, were determined for each patient. The mode of spaces between scatterers for liver cirrhosis was significantly larger than that for chronic hepatitis and nonspecific change. The mode of spaces between scatterers was correlated with the size of hepatic lobules or nodules. The kurtosis of spaces between scatterers for chronic hepatitis and liver cirrhosis was significantly smaller than that for nonspecific change. As a preliminary study for noninvasive application of this technique, cepstral analysis was also applied to the ultrasonogram obtained through the abdominal wall with a 3.5-MHz transducer. The results obtained with a 3.5-MHz transducer were correlated well with those obtained with a 10-MHz transducer. These results suggest the possibility of noninvasive evaluation of the structural changes in chronic liver disease.

Chronic Disease↗

PubMed1992

Atrial natriuretic peptide synthesis in atrial tumors of transgenic mice.

Transgenic mice harboring a chimeric gene linking mouse protamine 1 5'-flanking sequence to the coding sequence of the simian virus 40 T-antigen develop spontaneous rhabdomyosarcomas of the right atria. The presence of the tumors is accompanied by dramatic elevations in plasma atrial natriuretic peptide (ANP) immunoreactivity (1,698 +/- 993 vs. 60 +/- 18 fmol/ml for controls) and hematocrit (56 +/- 8 vs. 51 +/- 2 for controls). The immunoreactive ANP (irANP) present in the tumors is similar in size to irANP found in normal mouse atria. ANP mRNA transcripts present in the tumors also appear to be very similar in overall size and 5'-termini to those produced in normal cardiac tissue. Microscopically, the tumors are composed of a disorganized array of densely packed abnormal-appearing cells. Immunocytochemistry and in situ hybridization analysis reveal considerable heterogeneity in ANP gene expression. ANP peptide and mRNA are detectable throughout the parenchyma of the tumors, but absolute levels of expression vary widely among different cells in the population. These tumors represent a potentially valuable model for the study of inappropriate ANP secretion and may provide a tissue source for the development of an ANP-producing atrial cell line.

Amino Acid Sequence↗

PubMed1991

Isolation and ultrastructural analysis of microfibrillar structures from foetal bovine elastic tissues. Relative abundance and supramolecular architecture of type VI collagen assemblies and fibrillin.

Extensive intact assemblies of matrix macromolecules have been solubilized from foetal calf skin, nuchal ligament and aorta by a new procedure that includes bacterial collagenase digestion under non-reducing, non-denaturing conditions and gel filtration chromatography. Type VI collagen was identified as the major microfibrillar element of these tissues by SDS-PAGE analysis and Western blotting. Rotary shadowing electron microscopy of these preparations revealed by far the most abundant and extensive arrays of intact collagen VI microfibrils isolated to date. The distinct microfibrillar species, fibrillin, which was identified on the basis of its periodicity and morphology, was also solubilized in abundance by this protocol. Analysis of these complex polymers has generated new information on their supramolecular architecture and relative abundance in these tissues. The protocol also demonstrates that the release of intact collagen VI microfibrils from these tissues is largely dependent on the removal of the major collagen fibrils.

Animals↗

PubMedDate not supplied

Trypanosoma cruzi: serum antibody reactivity to the parasite antigens in susceptible and resistant mice.

The specific antibody responses were compared among susceptible (A/Sn), moderately susceptible (Balb/c) and resistant (C57 BL/10J) mice infected with Trypanosoma cruzi (Y strain). Sera obtained during the second week of infection recognized a surface trypomastigote antigen of apparent Mr 80 kDa while displaying complex reactivity to surface epimastigote antigens. Complex trypomastigote antigens recognition was detected around the middle of the third week of infection. No major differences were observed along the infection, among the three strains of mice, neither in the patterns of surface antigen recognition by sera, nor in the titres of antibodies against blood trypomastigotes (lytic antibodies), tissue culture trypomastigotes or epimastigotes. On immunoblot analysis, however, IgG of the resistant strain displayed the most complex array of specificities against both trypo and epimastigote antigens, followed by the susceptible strain. IgM antibodies exhibited a more restricted antigen reactivity, in the three mouse strains studied. Balb/c sera (IgG and IgM) showed the least complex patterns of reactivity to antigens in the range of 30 kDa to 80 kDa. The onset of reactivity in the serum to trypomastigote surface antigens was also dependent on the parasite load to which the experimental animal was subjected.

Animals↗

PubMed1992

Correlation between [5-3H]glucose and [U-14C]deoxyglucose as markers of glycolysis in reperfused myocardium.

Studies were conducted in extracorporeally perfused, intact, working pig hearts to determine whether, in heart muscle, trace-labeled deoxyglucose serves as an accurate marker of glycolytic flux in reperfusion after exposures to mild to moderate regional ischemia. In the main study, two groups of hearts were compared, as distinguished by levels of glucose in the whole-blood perfusate (euglycemic hearts [group I], blood glucose of 7.4 +/- 0.2 mumol/ml, n = 7; hyperglycemic hearts [group II], blood glucose of 12.9 +/- 0.5 mumol/ml, n = 8). Both groups were subjected to a 60% reduction in anterior descending coronary flow for 30 minutes followed by reperfusion for 40 minutes. Modest and comparable regional mechanical stunning during reflow was noted in both groups. Glucose utilization, as estimated from the release of 3H2O from the steady-state infusion of [5-3H]glucose during aerobic perfusion, was modest but during reperfusion was noted to increase significantly above aerobic values in each of the two groups, with a doubling of rates in group II hearts compared with group I hearts (p less than 0.041 or p less than 0.090). Net lactate extraction was comparable in reflow in both groups, suggesting in this specific instance a preferential enhancement of glucose oxidation in hyperglycemic group II hearts. Shifts in accumulation of tissue radioactivity of [U-14C]2-deoxyglucose in reperfused myocardium were not able to track these trends. The variability of 14C-labeled radioactivity among animals was marked and essentially masked any ability to discern trends in glycolysis as described by tritiated glucose between the aerobic and reperfusion intervals. When the data were arrayed by linear regression analysis, the slopes derived from 14C-labeled deoxyglucose were either discordant or insensitive to those described by 3H-labeled glucose. Tissue glycogen levels were slow to recover in early reflow and at end reperfusion were still significantly depressed from aerobic levels. The present data indicate that coronary reperfusion and hyperglycemia have influence in determining glycolytic flux in myocardium. Labeled deoxyglucose, considered solely as a marker of exogenous glucose utilization, appears to be an insensitive agent in describing these events at conditions of relatively low glucose flux.

Animals↗

PubMed2026

Integrative transcriptomic, spatial and functional-genomic analysis identifies a UFMylation-related vascular-stromal program and prioritizes WWTR1 in glioblastoma.

Glioblastoma (GBM) contains spatially organized stress-adaptive and vascular niches. Because transcript abundance does not measure UFM1 conjugation, we asked whether a UFMylation-related transcriptional axis identifies a reproducible tissue program and alters candidate prioritization. In 518 unique primary TCGA-GBM tumors profiled on the Affymetrix HT Human Genome U133A array, weighted gene co-expression network analysis of 8,000 variable genes yielded 12 modules. The 278-gene green module ranked first across nine prespecified traits (mean |r|=0.637). Direct overlap comprised 1/3 measurable UFMylation-core, 5/19 ER-stress/UPR, and 2/15 proteostasis genes; after excluding overlapping genes, correlations with the green eigengene remained significant (r = 0.373, 0.831, 0.639, and 0.699 for UFMylation-core, ER-stress/UPR, proteostasis, and composite scores, respectively). The green score was associated with overall survival per standard-deviation increase (HR 1.17, 95% CI 1.07-1.28), although clinical adjustment attenuated the estimate. In a 10-sample single-cell dataset, sample-level scores were higher in pericytes and endothelial cells than in malignant cells. Donor-aware IvyGAP analysis supported regional organization, whereas one Visium section showed stronger concordance with ER-stress/UPR and mesenchymal scores than with the UFMylation-core score. CellChat indicated pathway-selective rather than global remodeling of inferred vascular communication. Layer ablation moved WWTR1 from rank 48 using WGCNA alone to rank 4 overall and rank 1 among non-common-essential genes after cross-platform integration. These findings define an ER-stress/mesenchymal-weighted, UFMylation-related vascular-stromal transcriptional association and nominate WWTR1 for experimental testing.

Humans↗

PubMed1991

Human fetal central nervous system organotypic cultures.

Many aspects of human neurodevelopment remain enigmatic. A main reason for this is, although there have been a significant number of morphologic and biochemical studies of neural tissues derived from human embryos and fetuses, this can only provide a static picture of the events at a given gestational age. Also, in vitro studies that focus on cells derived from these tissues have a limitation in that different cell types in dissociated tissue culture cannot interact in a 'normal' physiologic manner thereby, perhaps, altering their housekeeping and luxury functions. The present study focused on the development of a human explant organotypic culture model that may overcome the static limitation of the first example and permit a dynamic analysis of different cell types as they interact which may satisfy the second restriction. Because there is an array of developmental markers that define different cell phenotypes, this explant model may also provide a means of analyzing, for the first time, processes undefined in the human CNS. Human fetal CNS tissue obtained from second trimester abortuses was established in culture. The tissues were maintained for up to 12 weeks during which time they developed and differentiated. Sample cultures were harvested periodically and analyzed by light- and electron microscopy in combination with immunocytochemistry. Differentiation of neurons, astrocytes, oligodendrocytes and endothelial cells was documented using morphologic and biochemical criteria. As such, this model system may allow for the analysis of processes that occur during normal human fetal neurodevelopment and in pathologic conditions.

Central Nervous System↗

PubMed1992

Analysis of oxygen exchange between arterioles and surrounding capillary-perfused tissue.

A theoretical model is used to analyze oxygen transport in a three-dimensional tissue region containing an arteriole surrounded by an array of capillaries in planes perpendicular to the arteriole. Convective removal of oxygen from the vicinity of the arteriole by nearby capillaries is shown to increase diffusive oxygen loss from the arteriole. This effect depends on the locations of the capillaries, particularly those nearest to the arteriole. The arteriolar oxygen efflux is comparable to that predicted by a previous model which used a continuum approach, but the efflux does not increase with increasing perfusion as rapidly as predicted by the continuum model. Even a small capillary flow rate strongly influences the oxygen field surrounding the arteriole.

Arterioles↗