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At least 19 recordsLinked to original sources
PubMed1977

Brain tumors of mixed tissue origin: staining procedures to distinguish glial from connective tissue.

Described is a unique mixed intracerebral tumor composed of schwannoma, piloid astrocytoma, and angiomatous malformation. Review of conventional staining methods for distinguishing glial from connective tissue fibrils reveals that Mallory's phosphotungstic acid-hematoxylin (PTAH) method is less specific than is generally recognized. Knowledge of these pitfalls, combined with use of hematoxylin and eosin stains, and reticulum impregnations are currently most useful in making the distinction by light microscopy. Criteria for malignancy of schwannoma and other mesenchymal tumors should be based on number of mitotic figures and invasiveness rather than on pleomorphiam of cells. Prior knowledge of the location of the tumor may lead to diagnosing some schwannomas as other types of tumor.

Adult↗
PubMed1979

Functional differentiation of mouse T lymphocytes. GVHR-precursors: tissue origin and specificity of activity inducer.

For theoretical and practical reasons, it is important to find out whether the differentiation of T cell precursors to the functional lymphocytes can be induced under in vitro conditions. Using the local GVHR assay (based on the enlargement of the popliteal lymph node), the inducibility of the precursors of reactive cells was studied with bone marrow, thymus, spleen, and lymph node cell suspensions submitted to short-term incubation with cell-free extracts from calf thymus, spleen or brain. GVHR-precursors from bone marrow were inducible not only specifically (i.e., with thymus extract) but also--and even to a higher degree--with spleen or brain extract. Thymus and spleen cell suspensions (the latter also depleted of the reactive subpopulation by treatment with anti-Thy 1.2 serum and complement) were, on the other hand, inducible mainly specifically, whereas lymph node cells were refractory to induction. The inductive action of tissue extracts obviously depends on the tissue origin of T cell precursors; their effects on pre- and postthymic differentiation of T lymphocytes are discussed.

Animals↗
PubMed1979

Metabolic inhibitors of host-tissue origin in Mycobacterium leprae.

It is not clear why host-derived bacteria are metabolically inert, compared to organisms grown in vitro. o-Diphenoloxidase is the only metabolic property proven to be present in Mycobacterium leprae separated from infected human as well as animal (mouse and armadillo) tissues. However, highly concentrated suspensions of M. leprae obtained from the organs of experimentally infected armadillos showed little or extremely low o-diphenoloxidase, while the organisms bound 14C-labeled dopa. When these preparations were diluted, they readily oxidized D-dopa to pigment. The activity remained unaltered by washing the suspensions with dilute alkali or acetone and ether, indicating that it is an intrinsic property of the bacilli. Treatment with different proteases relieved the inhibition, and resulted in a 100% stimulation of O-diphenoloxidase in the bacilli. Evidently, the M. leprae suspensions obtained from infected tissues contain an inhibitory material which is protein in nature, and the metabolic inertness sometimes observed in host-grown bacteria may not be due to loss of enzymes or metabolites from the organisms.

Animals↗
PubMed2026

Tissue origins of the plasma proteomic response to glucose ingestion in humans.

AIMS/HYPOTHESIS: Circulating proteins act as important hormonal signals of nutrient intake. We aimed to systematically characterise the time-resolved proteomic response to glucose ingestion in humans, and to assess its robustness following prolonged complete caloric restriction. METHODS: We conducted oral glucose tolerance tests (OGTTs) in 11 healthy volunteers before and after 7 days of complete caloric restriction and measured the response of >2900 targets through high-resolution plasma protein profiling. RESULTS: We identified a signature of 44 proteins that changed significantly following glucose ingestion, which was reproducible after 7 days without food, and was strongly (20-fold) enriched for 'stomach-specific' proteins. We report that annexin A10 (ANXA10) shows the most significant post-glucose change observed, similar to the trajectories of secreted hormones. We present observational human evidence from multiple sources suggesting that ANXA10 is secreted upon sensing an increase in gastric pH, with the stomach as the major contributing tissue. Despite a profound metabolic shift after 7 days of complete caloric restriction, characterised by delayed insulin secretion and postprandial hyperglycaemia, only four proteins showed robust evidence for a differential trajectory during both OGTTs. This included plasma levels of tryptophanyl-tRNA synthetase 1 (WARS), for which we found a genetic association with glucose homeostasis and coronary artery disease. CONCLUSIONS/INTERPRETATION: Our exploratory study identifies the proteomic response to glucose ingestion and demonstrates its reproducibility despite major shifts in glucose homeostasis. We characterise the gastrointestinal origin of these changes, and hypothesise a hitherto under-recognised role for sensing of changes in gastric pH on the plasma proteome.

Humans↗
PubMed2026

Cancer of unknown primary: the evolution of tissue of origin identification in the artificial intelligence era.

Cancer of Unknown Primary (CUP) presents substantial diagnostic and therapeutic challenges owing to its heterogeneous nature and the absence of an identifiable primary tumor site. This review provides a structured search of the pathogenesis, epidemiological characteristics, and limitations of traditional diagnostic and therapeutic approaches for CUP, with an emphasis on the evolution of Tissue of Origin (TOO) identification techniques. Recent advances in precision medicine have accelerated the development of machine learning-based TOO identification tools, representing a paradigm shift in CUP diagnostics. Deep learning (DL) algorithms that integrate multi-omics data (such as genomics and transcriptomics) with clinical features have markedly enhanced the accuracy of tracing tumor origin, and artificial intelligence (AI) driven TOO models are increasingly being incorporated into clinical practice, offering new insights for pathological diagnosis, treatment selection, and prognostic evaluation. Nevertheless, several challenges remain, including issues of data standardization, model generalizability, and interpretability. Ethical considerations related to data privacy, algorithmic fairness, and clinical implementation also warrant careful attention. Future research should focus on establishing standardized multi-center databases, developing more interpretable AI models, and fostering multidisciplinary collaborative strategies for CUP management. Through continued refinement of technical solutions and regulatory guidelines, TOO identification is anticipated to progress from research to routine clinical application, ultimately supporting precise and personalized care for patients with CUP.

Artificial intelligence↗
PubMed1978

Initial clinical evaluation of a new Rocky Mountain spotted fever vaccine of tissue culture origin.

Currently available Rocky Mountain spotted fever (RMSF) vaccines are relatively ineffective in preventing infections in humans and contain considerable amounts of contaminating egg protein. A new formalin-inactivated vaccine was prepared by sucrose density gradient centrifugation of the Sheila Smith strain of Rickettsia rickettsii grown in chick embryo cell tissue culture. The new product has greater protective immunogenicity in rheusus monkeys and guinea pigs than commercial vaccines. Six volunteers without immunologic evidence of prior exposure to RMSF received from one to three inoculations of the vaccine diluted 1:10, and there were two benign local reactions. Titers of antibody (determined by microagglutination and indirect fluorescence techniques) increased in all recipients as did lymphocyte tranformation responses to specific rickettsial antigen. Ten volunteers were immunized twice with vaccine diluted 1:3; there were no local reactions, and immunologic responses were similar to those in the six volunteers in the first group. The proper dosage and immunization schedule for the vaccine must be determined in further studies.

Agglutinins↗
PubMed1978

Desorption assay: a functional in vitro test for measuring the adhesion of E. coli on the urinary tract epithelium.

A functional test was developed to measure different adhesive properties of various Escherichia coli strains on the urinary tract epithelium. The test is based on initial incubation of everted canine ureteral segments in 2-hr cultures of E. coli (adsorption period), followed by sequential elutions in phosphate buffered saline. The release of bacteria (desorption rate) was measured from each elution by quantitative bacteriology. The function of the desorption assay was tested by showing different adhesive properties of various strains of E. coli. The strains isolated from infected canine urinary tracts showed high adhesion capacities superior to other strains of E. coli from different animal and/or tissue origin. This indicates a selective tissue and animal trophism determined by the strength of mucosal attachment. The test is also a valuable tool for measuring adhesion inhibiting substances in urine. The bulk of the adhesion inhibiting effect was localized in the urine ultrafiltrate.

Adhesiveness↗
PubMed2026

Single-cell multimodal profiling of pan-cancer cell lines uncovers gene regulatory principles underlying intrinsic cell states and environmental features.

Cancer arises from genetic and epigenetic alterations that reshape chromatin, transcriptional regulation, and malignant cell states. To chart cancer-intrinsic regulatory programs, we build a pan-cancer single-cell atlas of 60 cancer cell lines spanning 16 tissue origins and 20 cancer types, comprising 240,957 snRNA-seq and 223,347 snATAC-seq profiles. Integrative analyses reveal cell-state heterogeneity, core gene-regulatory networks, and a conserved EMT axis transcending tissue of origin; copy-number analysis identifies transcription factor amplification and hyperactivation as drivers of state reprogramming. Comparing cutaneous melanoma with acral melanoma, a rare subtype underrepresented in previous studies, uncovers a universal inflammation-suppressive program in acral and an inflamed landscape in cutaneous melanoma, with JAK-STAT activity as the central discriminator. Integrating data across models and patient cohorts links tumor-intrinsic regulation to microenvironmental composition and therapeutic response. By profiling rare alongside common subtypes, this atlas offers a resource for mapping pan-cancer and subtype-specific regulatory programs shaping cell-state plasticity.

Humans↗
PubMed2026

Exploring the transcriptional crosstalk between adipose tissue and locoregional recurrence in breast cancer using independent component analysis.

Locoregional recurrence (LRR) poses a persistent clinical challenge in breast cancer, with emerging evidence implicating the tumor-associated adipose tissue in modulating recurrence risk. This study investigates shared transcriptional programs between adipose tissue and breast tumors and examines their association with disease-free survival (DFS), particularly in the context of reconstructive surgery where adipose tissue from different body compartments are commonly used. We analyzed bulk gene expression data from 5,691 breast tumors and 978 human adipose tissue samples from different body compartments using consensus-independent component analysis (c-ICA) to identify transcriptional components (TCs). Gene set enrichment analysis (GSEA) and copy number alteration profiling were used for biological annotation. Associations between TCs and DFS were evaluated through univariate Cox regression. Key findings were validated using spatial transcriptomic and single-cell RNA sequencing datasets. Among the 411 TCs identified, 332 showed biological enrichment, and 35 were significantly associated with DFS. Four DFS-associated TCs (TC257, TC350, TC371, TC400) were enriched for adipogenesis-related genes and exhibited heightened activity in high-grade, triple-negative tumors and in patients with elevated BMI. Notably, TC350 was highly active in adipose tissue from common reconstructive donor sites (abdomen, omentum, subcutis) but not in native breast adipose tissue. Spatial transcriptomic and single-cell analyses confirmed the increased activity of these adipogenesis-related TCs in tumor regions and adipose cells. TC350 included FABP4, a gene previously linked to poor prognosis in breast cancer and considered as a potential new therapeutic target. Adipose tissue-derived transcriptional programs influence breast cancer prognosis and this seems to differ by tissue origin. These findings generate a hypothesis that donor site selection for adipose tissue in reconstructive surgery may impact LRR risk through adipogenesis-associated mechanisms. Further research is warranted to elucidate the biological and clinical implications of adipose-tumor transcriptional interactions.

Humans↗
PubMed1975

[Postmortem fibrinolysis and its biological characteristics].

Fibrinolysic cadaveric blood studied after a rapid death (strangulation asphyxia, traumatic and sudden death) contained no plasmin--an enzyme of fibrin destruction, and no plasminogen--its inactive precursor. In the absence of plasmin and plasminogen of interest is a high content of plasminogen activator. An increase in the content of the activator in the fibrinolysic blood exists along with a marked proactivator level. A relationshp between the concentration of the activator and the proactivator in this blood indirectly pointed to the intravascular (from the pre-existing blood proactivator of the living), and not the tissue origin of the activator. Activation of plasma proactivator is caused by the entrance of tissue lysokinases into the circulation.

Fibrinolysin↗
PubMed1977

[Immunologic and electrophoretic detection of an epidermal chalone-containing complex in tissues of different origin].

The rabbit antiserum to one of the components of the tissue-specific protein complex isolated from the back skin of rats and containing G1- and G2-chalones was obtained. By means of this antiserum an antigen identical to the cutaneous one was found in the mucous membrane of the tongue, oesophagus, prestomach and vagina, in the epidermis of the tail and sole. The cornea, mucous membranes of the urinary bladder and intestine, liver, kidney and blood serum do not contain this antigen. According to data of disc-electrophoresis in 5%-polyacrilamide gel, the 55--81% alcohol extracts of the investigated tissues of the epidermal type, including the cornea and mucous membrane of the urinary bladder, are of similar quantitative and qualitative composition, different from that of tissues of other origin.

Animals↗
PubMed1975

A human adrenocortical adenoma in tissue culture. Morphology and hormone secretion.

A human adrenocortical adenoma was cultivated in vitro and the morphological characteristics, steroidogenic activity and response to ACTH of the cultured cells were studied over a period of about two months. At first, the morphology of the cultures was similar to that of the original tissue. This structure changed in the course of time and the cells underwent fibroblastoid transformation. Stimulation with ACTH evoked two types of morphological response: a) a short-term response, whereby an extensive but rapidly reversible vacuolization was followed by cell enlargement and granulation, and b) a long-term effect in which the differentiated cell morphology was maintained. The cultures showed a low steroidogenic activity throughout the experiment. ACTH stimulation increased the total 17-hydroxysteroid production up to 10-fold. After ACTH withdrawal the corticosteroid levels declined slowly and about 50% of the maximal activity persisted on the fifth day after ACTH withdrawal.

Adenoma↗
PubMed1979

Expression of monocytic--histiocytic cytochemical markers in epithelial neoplasia.

The diagnosis of malignant histiocytosis is usually based upon typical light microscopic features of the neoplasm. Supplementary cytochemical and immunologic features have been suggested as typical of malignant histiocytosis. The present study was prompted by an unusual erythropagocytic hepatocellular carcinoma having immunologic and cytochemical markers suggesting mononuclear phagocytic origin. Twenty-four neoplasms of unquestionable epithelial origin were prospectively evaluated for activity of alpha-naphthyl acetate esterase, a cytochemical marker useful in distinguishing between the non-Hodgkin's lymphomas and malignant histiocytosis. The epithelial tumors represented a broad spectrum of tissue origins and consistently demonstrated alpha-naphthyl acetate esterase activity. Thus, erythrophagocytosis and alpha-naphthyl acetate esterase positivity may be misleading in the unusual instance in which the histopathologic differential diagnosis includes malignant histiocytosis and epithelial neoplasia. Ultrastructural assessment is useful in the exclusion of poorly differentiated carcinoma.

Carboxylic Ester Hydrolases↗
PubMedDate not supplied

[Various biological properties of diploid cell strains derived from various tissues of human embryo].

Some properties of 4 diplod cell strains derived from the lung and skin-muscle tissue of human embryos were studied. Only one strain (L-63) was shown to have a stable karyotype throughout its life span and induced no tumor formation in the cheek pouch of hamsters. Species-specific and group antigens were revealed. In the cell strains of the lung and skin-muscle derivation differences in the distribution of lactate dehydrogenase isoenzymes were observed and found characteristic of the original tissue cells.

Animals↗
PubMed1977

The derivation and characterization of neuronal cell lines from rat and mouse brain.

This study shows that permanent cell lines can be established from rat and mouse brain by direct tissue culture methodology without the aid of exogenous chemical or viral transforming agents. These cells were derived from specific areas of the brain, such as the cerebellum and hippocampus, at chosen times during fetal and neonatal development. Success in establishing neuronal cell lines was dependent upon the use of selection pressures designed to keep the background of glial cells and fibroblasts at a minimum. These manipulations included care in the choice and processing of the original tissue, utilization of cytotoxic anti-glial sera, and continuous manual isolation of cells with neuronal morphology. Slow-growing nerve cells were thus allowed to adapt spontaneously to culture with a minimum of competition from faster-adapting cell types. Many of these cell lines are judged to be neuronal on the basis of their electrical excitability and their characteristic surface antigens. The cells respond positively in a sodium flux assay which has been shown to correlate well with the ability to generate an action potential, and also express one or more of three antigens previously found to be specific for nerve cells.

Animals↗
PubMed1979

Evidence of a mixed population from uterine tube epithelium in a continuous line of pig cells.

The pig uterine tube (PFT) cell line is composed of a mixed population which is undifferentiated. However, specific markers indicating the original tissue of the uterine tube were shown if cells differentiated into epithelial cells forming spheroids in the 254th subculture. Ciliated and secretory cells, and cells with a basal lamina and interstitial collagen were observed in the spheroids. Microlumina found in the spheroids appeared morphologically similar to the lumen of the uterine tube. These observations indicate that undifferentiated cells can multiply in vitro and keep their potentiality of differentiation for future expression. It is proposed that the PFT cell line was partly derived from epithelial cells originally harvested from the PFT.

Animals↗
PubMed1976

Phospholipid removal during degradation of rat plasma very low density lipoprotein in vitro.

The hydrolysis of glycerophospholipids in very low density lipoprotein by enzyme(s) released into circulation after the injection of heparin to rats was studied. [32P]Lysolecithin was formed rapidly from [32P]lecithin when very low density lipoprotein, labeled biosynthetically with 32P, was incubated with postheparin plasma. The [32P]lysolecithin was associated with the plasma protein fraction of density greater than 1.21 g/ml, whereas [32P]lecithin exchanged between very low and high density lipoproteins. Inhibition of the plasma lecithin: cholesterol acyl transferase activity did not change the excess [32P]lysolecithin formation in postheparin plasma, and only a negligible amount of radioactivity was associated with blood cells when the incubation was repeated in whole blood. Analysis of the results has demonstrated that phospholipids are removed from VLDL by two pathways: hydrolysis of glycerophospholipids by the heparin-releasable phospholipase activity (greater than50%) and transfer to high density lipoproteins (less than50%). The tissue origin of the postheparin phospholipase was studied in plasma obtained from intact rats and supradiaphragmatic rats using specific inhibitors of the extrahepatic lipase system (protamine sulfate and 0.5 M NaCl). The phospholipase activity could be ascribed to both the hepatic and extrahepatic lipase systems. It is concluded that hydrolysis of glycerophospholipids is the major mechanism responsible for the removal of phospholipids from very low density lipoprotein during the degradation of the lipoprotein. It is suggested that phospholipid hydrolysis occurs concomitantly with triglyceride hydrolysis, predominantly in extrahepatic tissues.

Animals↗