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Acta Pathologica Japonica Apr 1990To elucidate the relationship between cell proliferation and structural remodeling in pulmonary fibrosis, light and electron microscopy with immunohistochemistry for...
To elucidate the relationship between cell proliferation and structural remodeling in pulmonary fibrosis, light and electron microscopy with immunohistochemistry for bromodeoxyuridine (BrdU) and morphometry for BrdU-positive cells were performed following a single intratracheal instillation of bleomycin in rats. The results showed that terminal bronchiolar epithelial cells, Type II alveolar epithelial cells and interstitial cells began to proliferate 2 days after the injury. Then each cell type showed a different style of proliferation. Interstitial cells which were located in the interstitium and migrated into intraalveolar spaces proliferated, then produced intra-alveolar fibrosis. Terminal bronchiolar epithelial cells proliferated rapidly and formed alveolar bronchiolization with squamous metaplasia in areas where alveoli were severely damaged and intraalveolar fibrosis was formed, and thereafter the proliferation ceased within 2 weeks. The degree of proliferation of type II alveolar epithelial cells and interstitial cells was rather slight, but continued constantly until the later stage. In addition, intraalveolar macrophages were BrdU-positive from an early stage. Endothelial cell proliferation was observed in small vessels and alveolar capillaries at 1 week after bleomycin instillation. Rapidly proliferating bronchiolar epithelial cells which formed alveolar bronchiolization with squamous metaplasia were important in preventing the progress of intraalveolar fibrosis, because the proliferation of type II alveolar epithelial cells was limited.
Topics: Administration, Oral; Animals; Bleomycin; Bromodeoxyuridine; Cell Division; Cell Nucleus; DNA; Endothelium; Epithelium; Female; Immunohistochemistry; Lung; Macrophages; Microscopy, Electron; Pulmonary Fibrosis; Rats; Rats, Inbred Strains; Time Factors
PubMed: 1695413
DOI: 10.1111/j.1440-1827.1990.tb01556.x -
The Journal of Experimental Medicine Jun 1995Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that binds to major histocompatibility complex class II molecules and selectively interacts with T cells...
Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that binds to major histocompatibility complex class II molecules and selectively interacts with T cells that bear certain T cell receptor (TCR) V beta domains. Administration of SEB in adult mice results in initial proliferation of V beta 8+ T cells followed by a state of unresponsiveness resulting from a combination of clonal deletion and clonal anergy in the SEB-reactive population. At this time, it is unclear what relationship exists between the T cells that have proliferated and those that have been deleted or have become anergic. Here we show that only a fraction of the potentially reactive V beta 8+ T cells proliferate in response to SEB in vivo, and that all the cells that have proliferated eventually undergo apoptosis. Virtually no apoptosis can be detected in the nonproliferating V beta 8+ T cells. These data demonstrate a causal relationship between proliferation and apoptosis in response to SEB in vivo, and they further indicate that T cells bearing the same TCR V beta segment can respond differently to the same superantigen. The implications of this differential responsiveness in terms of activation and tolerance are discussed.
Topics: Animals; Apoptosis; Bromodeoxyuridine; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Clonal Anergy; Enterotoxins; Flow Cytometry; Kinetics; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Receptors, Antigen, T-Cell, alpha-beta; Staphylococcus aureus; Superantigens; T-Lymphocyte Subsets; T-Lymphocytes
PubMed: 7760014
DOI: 10.1084/jem.181.6.2283 -
Neural Plasticity 2014Besides dopamine-deficiency related motor symptoms, nonmotor symptoms, including cognitive changes occur in Parkinson's disease (PD) patients, that may relate to...
Besides dopamine-deficiency related motor symptoms, nonmotor symptoms, including cognitive changes occur in Parkinson's disease (PD) patients, that may relate to accumulation of α-synuclein in the hippocampus (HC). This brain region also contains stem cells that can proliferate. This is a well-regulated process that can, for example, be altered by neurodegenerative conditions. In contrast to proliferation in the substantia nigra and subventricular zone, little is known about the HC in PD. In addition, glial cells contribute to neurodegenerative processes and may proliferate in response to PD pathology. In the present study, we questioned whether microglial cells proliferate in the HC of established PD patients versus control subjects or incidental Lewy body disease (iLBD) cases as a prodromal state of PD. To this end, proliferation was assessed using the immunocytochemical marker minichromosome maintenance protein 2 (MCM2). Colocalization with Iba1 was performed to determine microglial proliferation. MCM2-positive cells were present in the HC of controls and were significantly increased in the presymptomatic iLBD cases, but not in established PD patients. Microglia represented the majority of the proliferating cells in the HC. This suggests an early microglial response to developing PD pathology in the HC and further indicates that neuroinflammatory processes play an important role in the development of PD pathology.
Topics: Aged; Aged, 80 and over; Cell Proliferation; Female; Hippocampus; Humans; Male; Microglia; Parkinson Disease; Prodromal Symptoms; alpha-Synuclein
PubMed: 25197578
DOI: 10.1155/2014/959154 -
The American Journal of Physiology Dec 1990Transgenic mice expressing atrial natriuretic factor-SV40 T-antigen fusion genes (ANF-TAG) developed unilateral right atrial tumors composed of differentiated dividing...
Transgenic mice expressing atrial natriuretic factor-SV40 T-antigen fusion genes (ANF-TAG) developed unilateral right atrial tumors composed of differentiated dividing cardiomyocytes. The atrial tumors could be propagated as transplantable tumor lineages in syngeneic animals. Cardiomyocytes derived from ANF-TAG atrial tumors did not proliferate in tissue culture. However, cardiomyocytes derived from the transplantable tumor lines proliferated in culture, and these proliferating cardiomyocytes could be passaged in culture and recovered from frozen stocks. Cardiomyocytes from either tumor source were highly differentiated as determined by diverse functional and structural criteria. The cells continued to express numerous cardiac-specific proteins and retained ultrastructural features characteristic of cardiomyocytes including well-formed myofibrils, transverse tubules, and intercalated disks. In addition, the cultured cells displayed spontaneous electrical and contractile activities. These atrial tumor cardiomyocytes are a novel experimental resource for the identification of genes regulating the cardiomyocyte cell cycle.
Topics: Animals; Antigens, Viral, Tumor; Atrial Natriuretic Factor; Cell Differentiation; Cell Division; Cells, Cultured; Cloning, Molecular; Culture Techniques; Heart Atria; Heart Transplantation; Mice; Mice, Transgenic; Myocardium; Neoplasm Transplantation; Phenotype; Simian virus 40; Tumor Cells, Cultured
PubMed: 2175567
DOI: 10.1152/ajpheart.1990.259.6.H1826 -
The International Journal of... Mar 2010Neurogenesis in the hippocampus continues throughout adult life and can be regulated by the local microenvironment. To determine whether denervation stimulates...
Neurogenesis in the hippocampus continues throughout adult life and can be regulated by the local microenvironment. To determine whether denervation stimulates neurogenesis in hippocampus, proliferation, migration, and differentiation of local neural stem cells (NSCs) in dentate gyrus was investigated after fimbria fornix transection. In the denervated hippocampus, NSCs proliferated markedly and migrated along the subgranular layer, and more newborn cells differentiated into neurons or astrocytes. After denervation, more newborn cells in the deafferented hippocampus expressed Brn-4 and differentiated into beta-Tubulin III positive neurons. It is concluded that the local NSCs in hippocampus may proliferate and migrate into granule cell layer, in which changes in the deafferented hippocampus provided a suitable microenvironment for hippocampal neurogenesis and the increased Brn-4 in denervated hippocampus may be involved in this process.
Topics: Adult Stem Cells; Animals; Astrocytes; Cell Movement; Cell Proliferation; Female; Fornix, Brain; Hippocampus; Nerve Tissue Proteins; Neurogenesis; Neurons; POU Domain Factors; Rats; Rats, Sprague-Dawley; Staining and Labeling; Tubulin
PubMed: 20374086
DOI: 10.3109/00207450903464579 -
The British Journal of Dermatology May 2016Fluorescence excitation provides the ability to interrogate innate molecules whose radiation emission correlates with specific functional states of tissue.
BACKGROUND
Fluorescence excitation provides the ability to interrogate innate molecules whose radiation emission correlates with specific functional states of tissue.
OBJECTIVES
The present study demonstrates the effectiveness of a novel ultraviolet (UV) fluorescence excitation photography system in its ability to image rapidly proliferating epidermal skin lesions by capturing endogenous fluorescence emissions attributed to tryptophan.
METHODS
A clinical prototype UV fluorescence excitation photography system was used to acquire images of endogenous fluorescence ascribed to tryptophan.
RESULTS
Twelve human subjects and 11 ex vivo samples with various skin lesions consistently exhibited increased endogenous fluorescence at 340-nm wavelength upon excitation at 295 nm in rapid epidermal proliferations, including psoriasis, actinic keratoses and basal cell carcinoma, compared with surrounding normal skin. In contrast, nonproliferating lesions showed decreased fluorescence.
CONCLUSIONS
This simple but robust point-and-shoot imaging system may offer a clinically useful, noncontact, noninvasive device for the diagnosis and detection of skin disease. As opposed to structural imaging modalities, fluorescence excitation imaging at 295/340-nm wavelengths offers high-sensitivity, wide-field functional imaging of cellular proliferation without the need for externally applied dyes or lengthy image processing. Furthermore, the image is instantly available and does not require interpretation or reconstruction.
Topics: Cell Proliferation; Epidermis; Humans; Photography; Skin Diseases; Spectrometry, Fluorescence
PubMed: 26783740
DOI: 10.1111/bjd.14400 -
Biology of Reproduction Jan 2014Conventionally, it was believed that Sertoli cells (SC) stopped proliferating at puberty and became terminally differentiated quiescent cells. However, recent studies...
Conventionally, it was believed that Sertoli cells (SC) stopped proliferating at puberty and became terminally differentiated quiescent cells. However, recent studies have challenged that dogma. In this study, we transplanted nondividing SC isolated from 23- to 27-day-old postpubertal rats transduced with a recombinant adenoviral vector (containing furin-modified human proinsulin cDNA) into diabetic severe combined immunodeficiency mice. Immunostaining the grafts for cell proliferation markers, proliferating cell nuclear antigen (PCNA) and MKI67, revealed that transplanted SC within the grafts were proliferating. Possible causes for resumption of proliferation of SC could be viral transduction, cell isolation and culture, higher abdominal temperature at the transplant site, and/or transplantation. To test for these possible causes, double- immunofluorescence staining was performed for GATA4 (SC marker) and MKI67. None of the SC were positive for MKI67 in tissue collected during SC isolation and culture or at higher temperature. However, nontransduced SC stained positive for MKI67 after transplantation into rats, suggesting viral transduction was not a key factor for induction of SC proliferation. Interestingly, resumption in proliferative ability of nondividing SC was temporary, as SC stopped proliferating within 14 days of transplantation and did not proliferate thereafter. Quantification of 5-bromo-2'-deoxyuridine-labeled SC demonstrated that 7%-9% of the total transplanted SC were proliferating in the grafts. These data indicate for the first time that nondividing SC resumed proliferation after transplantation and further validate previous findings that SC are not terminally differentiated. Hence, transplantation of SC could provide a useful model with which to study the regulation of SC proliferation in vivo.
Topics: Animals; Cell Division; Cell Proliferation; Cells, Cultured; Male; Mice; Mice, Inbred NOD; Mice, SCID; Rats; Rats, Inbred Lew; Rats, Inbred WF; Sertoli Cells; Sexual Maturation
PubMed: 24285718
DOI: 10.1095/biolreprod.113.110197 -
The Anatomical Record Sep 1998Previous studies of colonic epithelial cell kinetics in mice and rats revealed a pattern similar to small intestine, where basally located stem cells proliferate,...
Previous studies of colonic epithelial cell kinetics in mice and rats revealed a pattern similar to small intestine, where basally located stem cells proliferate, differentiating as they migrate towards the surface epithelium. Vacuolated and goblet cells are assumed to co-migrate at the same rate. The present study indicates that rabbit distal colon has more complicated epithelial cell kinetics. The zone of proliferation was detected immunohistochemically using proliferating cell nuclear antigen (PCNA) and confirmed with the use of colchicine to arrest dividing cells in metaphase. Migrating cells were tracked from the zero-hour position (PCNA labeling, mitosis) to positions 24, 48, 72 hrs by monitoring cell migration with the thymidine analog 5-Bromo-2-Deoxyuridine (BrdU). PCNA revealed a major proliferative zone in the upper third of the crypt column and the presence of mitotic figures after colchicine corroborated these results. Differentiated vacuolated cell proliferation was detected at three crypt sites: base, middle, and top of the crypt, while columnar cells arose from a population of dividing cells at the top of the crypt. Turnover of columnar and vacuolated cells occurred within 72 hrs. Goblet cells exhibited maximal proliferation at the crypt base and migrated at a much slower rate than the other cell types. In rabbit distal colon, populations of proliferating cells exist at multiple levels of the crypt column. Vacuolated and goblet cells differ in their labeling indices and migration rates, suggesting that the two cell types arise and migrate independently.
Topics: Animals; Antimetabolites; Bromodeoxyuridine; Cell Division; Colchicine; Colon; Female; Goblet Cells; Proliferating Cell Nuclear Antigen; Rabbits; Specific Pathogen-Free Organisms; Vacuoles
PubMed: 9737743
DOI: 10.1002/(SICI)1097-0185(199809)252:1<41::AID-AR5>3.0.CO;2-H -
Atherosclerosis Nov 1999Monocytes (MPhis) are among the first cells to accumulate in early atherosclerotic lesions and generally are believed to be incapable of proliferation. However, recent...
Monocytes (MPhis) are among the first cells to accumulate in early atherosclerotic lesions and generally are believed to be incapable of proliferation. However, recent studies indicate that the number of MPhis in atherosclerotic lesion may increase due to induction of local proliferation. Since proliferation of hematopoietic lineage cells is strongly influenced by interaction with neighboring cell types, we examined the ability of vascular endothelial cells (EC), smooth muscle cells or fibroblasts to stimulate MPhi proliferation. In this study, we show that only when seeded at high densities MPhis could proliferate in culture. However, when contact co-cultured with EC, MPhis proliferated at a higher rate (260% on day 6) than those cultured alone or co-cultured with smooth muscle cells or fibroblasts. Endothelial cells could stimulate the proliferation of MPhis even at non-proliferating densities. Only EC that were growth arrested or in lag phase could induce MPhi proliferation, whereas those in the exponential proliferating phase were non-stimulatory. Conditioned medium prepared from EC in growth arrested or lag phase failed to stimulate MPhi proliferation. Similarly physical separation of MPhis from EC also resulted in no proliferation. These results suggest that EC induced MPhi proliferation is contact dependent and no soluble factors are involved in this induction. This EC induced MPhi proliferation may have a profound effect on the rate of progression of atherosclerosis.
Topics: Cell Division; Cells, Cultured; Coculture Techniques; Culture Media, Conditioned; Endothelium, Vascular; Fibroblasts; Humans; Monocytes; Muscle, Smooth, Vascular
PubMed: 10525121
DOI: 10.1016/s0021-9150(99)00144-6 -
Blood Mar 1981Lymphocytes from 6 patients with chronic lymphocytic leukemia of the B-cell variety (B-CLL) were cultured with equal numbers of mitomycin-treated mononuclear cells from...
Lymphocytes from 6 patients with chronic lymphocytic leukemia of the B-cell variety (B-CLL) were cultured with equal numbers of mitomycin-treated mononuclear cells from normal blood. When stimulated with pokeweed mitogen (PWM), phytohemagglutinin (PHA), or the tumor-promoting agent, phorbol tetradecanoyl-acetate (TPA), the CLL cells proliferated actively by day 3 or 4 of culture, and in four cases, differentiated to significant numbers of immunoglobulin-containing cells. Chromosome studies on the proliferating lymphocytes demonstrated a cytogenetically abnormal clone in three patients, including two with a 14q+ marker chromosome and two with a translocation involving the short arm of chromosome 9. One patient had a translocation from 22q to 14q, producing a Philadelphia chromosome as well as the 14q+ marker. The results indicate that the neoplastic lymphocytes of B-CLL may proliferate and differentiate when appropriately stimulated in vitro, and that chromosomally abnormal clones are not uncommon. With several techniques now available for successful short-term culture of B-CLL lymphocytes, there is opportunity for better understanding of the cellular alterations in this disease.
Topics: B-Lymphocytes; Cell Differentiation; Chromosome Aberrations; Chromosomes, Human, 21-22 and Y; Chromosomes, Human, 6-12 and X; Humans; Leukemia, Lymphoid; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Mitomycins; Translocation, Genetic
PubMed: 6450621
DOI: No ID Found