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Results for “Granulation Tissue”

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At least 451 records · Page 25Linked to original sources
PubMed2000

Thrombospondin-1 suppresses wound healing and granulation tissue formation in the skin of transgenic mice.

The function of the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1) in tissue repair has remained controversial. We established transgenic mice with targeted overexpression of TSP-1 in the skin, using a keratin 14 expression cassette. TSP-1 transgenic mice were healthy and fertile, and did not show any major abnormalities of normal skin vascularity, cutaneous vascular architecture, or microvascular permeability. However, healing of full-thickness skin wounds was greatly delayed in TSP-1 transgenic mice and was associated with reduced granulation tissue formation and highly diminished wound angiogenesis. Moreover, TSP-1 potently inhibited fibroblast migration in vivo and in vitro. These findings demonstrate that TSP-1 preferentially interfered with wound healing-associated angiogenesis, rather than with the angiogenesis associated with normal development and skin homeostasis, and suggest that therapeutic application of angiogenesis inhibitors might potentially be associated with impaired wound vascularization and tissue repair.

Animals↗
PubMed1996

Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor.

Connective tissue growth factor (CTGF) is a 36-to 38-kDa peptide that is selectively induced by transforming growth factor-beta (TGF-beta) in fibroblastic cell types. We compared the biologic activities of CTGF with TGF-beta on fibroblasts in culture and in animal models of fibroplasia. CTGF was active as a mitogen in monolayer cultures of normal rat kidney fibroblasts. CTGF did not stimulate anchorage-independent growth of NRK fibroblasts, however, or inhibit the growth of mink lung epithelial cells, distinguishing CTGF's growth-regulatory activities from those of TGF-beta. In NRK fibroblasts, both TGF-beta and CTGF significantly increased the transcripts encoding alpha 1 type I collagen, alpha 5 integrin, and fibronectin. Stimulation of type I collagen and fibronectin protein synthesis by TGF-beta and CTGF was confirmed by pulse labeling of cells with [35S]methionine. Subcutaneous injection of TGF-beta and CTGF into neonatal NIH Swiss mice resulted in a large stimulation of granulation tissue and fibrosis at the site of injection. In situ hybridization studies revealed that TGF-beta injection induced high levels of CTGF mRNA in the dermal fibroblasts at the injection site, demonstrating that TGF-beta can induce the expression of CTGF in connective tissue cells in vivo. No CTGF transcripts were detected in the epidermal cells in either control or TGF-beta-injected skin or in fibroblasts in control (saline-injected) skin. These results demonstrate that, like TGF-beta, CTGF can induce connective tissue cell proliferation and extracellular matrix synthesis.

Animals↗
PubMedDate not supplied

Postoperative spindle cell nodules (PSCN) resembling sarcomas: an atypical granulation tissue or atypical pyogenic granuloma with exuberant myofibroblastic component?

Three cases of PSCN that developed 6-8 weeks after operations to the lower genital tract in two women, and after tooth removal in a 9-year-old boy are described. The lesions averaged 2 cm. in diameter and simulated spindle cell sarcomas because of their high mitotic rate, and marked cellularity. On follow-up (2-6 years) all patients were found to be free of disease. Immunohistochemical testing of the spindle cells showed a strong positivity for vimentin, and muscle actin and a weak, focal and inconstant positivity for F. VIII R.A., and Ulex E. The was total negativity for desmin, smooth muscle actin, S 100 Protein and Cytokeratins. We believe that these lesions represent an atypical form of granulation tissue in which the exuberant myofibroblastic component obscure the vascular elements of the lesion.

Adult↗
PubMed1992

Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography.

While 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is a useful tumor imaging agent, its intratumoral distribution has not been described well at the cellular level. In order to demonstrate cellular localization of [18F]FDG and 2-deoxy-D-[3H]glucose (3H-DG) uptake by the tumor in vivo, C3H/He mice transplanted subcutaneously with FM3A tumors were studied 1 hr after intravenous injection of [18F]FDG or 3H-DG using micro- and macro-autoradiography. Fluorine-18-FDG and 3H-DG showed the same distribution pattern in the tumor with both autoradiographic methods. The newly formed granulation tissue around the tumor and macrophages, which were massively infiltrating the marginal areas surrounding necrotic area of the tumor showed a higher uptake of [18F]FDG than the viable tumor cells. A maximum of 29% of the glucose utilization was derived from nontumor tissue in this tumor. The comparison of double-tracer autoradiographic distribution patterns of [18F]FDG and [6-3H]-thymidine showed the differences and the similarities between glucose utilization and the DNA synthesis. Whole proliferating tissue metabolizes [18F] FDG but not vice versa. High accumulation of [18F]FDG in the tumor is believed to represent high metabolic activity of the viable tumor cells. Our results showed that one should consider not only the tumor cells proper but also the non-neoplastic cellular elements, which appear in association with growth or necrosis of the tumor cells, for precise analysis of [18F]FDG uptake in tumor-bearing subjects, especially after anti-neoplastic treatment.

Animals↗
PubMed1992

Immunocytochemically detectable metallothionein in granulation tissue surrounding mucosal ulceration.

Metallothioneins (MTs) are low-molecular-weight heavy metal binding proteins which are effective free oxygen radical scavengers in vitro. Free oxygen radicals have been implicated in the pathogenesis of stress-induced acute gastric mucosal ulceration and ischaemic injury in rat and man. Experimentally, MTs can have a protective role in stress-induced ulceration in rats. The possible cytoprotective role of MTs in chronic mucosal ulceration in man has not been previously studied. Evidence for locally produced MTs in human chronic gastric and small bowel ulcers has been sought by immunocytochemical staining using a monoclonal antibody (E9) to MT. At the base of ulcers MT has been localized to spindle cells (fibroblasts) in granulation tissue. Labelling of macrophages with a pan-macrophage marker KP1, and double labelling with KP1 and E9 showed two distinct populations, and MT appeared to be localized primarily in fibroblast-like cells.

Antibodies, Monoclonal↗
PubMed2007

Inhibition of Fas-associated apoptosis in granulation tissue cells accompanies attenuation of postinfarction left ventricular remodeling by olmesartan.

Blockade of angiotensin II type 1 receptor (AT1) signaling attenuates heart failure following myocardial infarction (MI), perhaps through reduction of fibrosis in the noninfarcted myocardium. However, its specific effect on the infarct tissue itself has not been fully clarified, which we examined in the present study. After MI induction in mice, treatment with the AT1 blocker olmesartan, beginning on the 3rd day post-MI, significantly improved survival (94%) 4 wk post-MI, compared with saline (53%) and hydralazine (73%). Olmesartan-treated mice also showed significant attenuation of left ventricular dilatation and dysfunction, as well as significantly greater infarct wall thickness, although the absolute size of the infarct scar was unchanged. In addition, significantly greater numbers of nonmyocytes (mainly vascular cells and myofibroblasts) were present within the infarct scar in olmesartan-treated hearts. Ten days post-MI, apoptosis among granulation tissue cells was significantly suppressed in the olmesartan-treated hearts, where expression of Fas, Bax, procaspase-3, and Daxx and activation of caspase-3, c-Jun NH(2)-terminal kinase, and c-Jun were all significantly attenuated. By contrast, expression of Fas ligand, Bcl-2, and Fas-associated death domain and activation of caspase-8 were unaffected, suggesting olmesartan exerts a negative regulatory effect on the alternate pathway downstream of Fas receptor. In vitro, olmesartan dose-dependently inhibited Fas-mediated apoptosis in granulation tissue-derived myofibroblasts. The present study proposes this antiapoptotic effect as another important mechanism for an AT1 blocker in improving post-MI ventricular remodeling, as well as its antifibrotic effect, and also suggests a significant link between renin-angiotensin and Fas/Fas ligand systems in postinfarction hearts.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2001

Keratinocyte-derived granulocyte-macrophage colony stimulating factor accelerates wound healing: Stimulation of keratinocyte proliferation, granulation tissue formation, and vascularization.

Chronic, nonhealing wounds represent a major clinical challenge to practically all disciplines in modern medicine including dermatology, oncology, surgery, and hematology. In skin wounds, granulocyte-macrophage colony stimulating factor (GM-CSF) is secreted by keratinocytes shortly after injury and mediates epidermal cell proliferation in an autocrine manner. Many other cells involved in wound healing including macrophages, lymphocytes, fibroblasts, endothelial cells, and dendritic cells synthesize GM-CSF and/or are targets of this cytokine. Therefore, GM-CSF is a pleiotropic cytokine evoking complex processes during wound repair. Despite this complexity and the scarcity of mechanistic understanding GM-CSF has been employed in trials of clinical treatment of skin wounds with some success. In this study, we evaluated a transgenic mouse model in order to analyze the effects of an excess of keratinocyte-derived GM-CSF on excisional wound healing in the skin. Transgenic mice constitutively overexpressing GM-CSF in the basal layer of the epidermis displayed accelerated reepithelialization of full-thickness skin wounds. In the early stages of wound repair, transgenic mice exhibited significantly higher numbers of proliferating keratinocytes at the wound edges and increased formation of granulation tissue with enhanced neovascularization. As a potential mechanism of these beneficial changes, we identified the differential temporal regulation of cytokines such as transforming growth factor-beta, a known angiogenetic factor, interferon-gamma, a proinflammatory cytokine, and interleukin 6, an essential factor for reepithelialization, in transgenic mice versus controls. We propose that the beneficial effects observed in GM-CSF transgenics are due not only to direct GM-CSF action but in addition to indirect processes via the induction of secondary cytokines.

Animals↗
PubMed1987

A dose-response study of the effects of biosynthetic human growth hormone on formation and strength of granulation tissue.

The dose-response relationship between biosynthetic human GH (b-hGH) and biomechanical properties (maximum stress, strain at maximum stress, relative failure energy, and maximum stiffness) and collagen deposition of granulation tissue in sc implanted cellulose sponges were investigated after 7 days of implantation in female rats. GH was administered in doses of 0.5, 2.0, and 8.0 mg/kg body weight/day. In the first part of the experiment, treatment with b-hGH started 7 days before implantation of the sponges, in the second part at the day of implantation, and for the 2.0 mg also 2 days before implantation. When b-hGH treatment was started 7 days before implantation, collagen deposition, maximum stress, and maximum stiffness were increased in the sponges from all the hormone-treated groups. In the group treated with 2.0 mg b-hGH/kg body weight.day, also an increase in failure energy was found. When b-hGH treatment was started at the day of implantation or 2 days before implantation, no differences in collagen deposition and biomechanical parameters were found. B-hGH treatment resulted in an increased weight gain in all three groups in the period before implantation, but only 8.0 mg b-hGH/kg body weight resulted in an increased weight gain during the following implantation period. The groups starting hormone treatment at the day of implantation showed an increased weight gain during the implantation period. The study shows that mechanical strength and collagen formation in sc implanted cellulose sponges in rats are increased by b-hGH when treatment is started 7 days before implantation with a maximum increase at a dose of 2.0 mg b-hGH/kg body weight.day.

Animals↗
PubMed1975

Changes in numbers of acidophilic and basophilic connective tissue granulated cells in the intestine of the rat during the estrous cycle.

Changes in physiological reproductive states of female Long-Evans hooded rats were directly correlated with changes in the concentration of acidophilic and basophilic connective tissue granulated cells in the lamina propria of the duodenum. Acidophilic granulated cell numbers were significantly higher at estrus and metestrus than at other stages of the estrous cycle or in the immature state. apcidophilic granulated cell numbers during pregnancy were not significantly different from cell numbers quantified during metestrus, diestrus, or proestrus, but were significantly lower than cell numbers during estrus. Late lactation (21-25 days) was associated with significant decreases in the numbers of acidophilic granulated cells from numbers observed during the estrous cycle and during pregnancy. Basophilic granulated cell numbers did not differ significantly during the estrous cycle, although the highest numbers were observed during proestrus. Basophilic granulated cell numbers were significantly higher during pregnancy than during the estrous cycle. Basophilic granulated cell counts in late lactation were comparable to numbers quantified in estrus, metestrus, and diestrus, but were significantly lower than during proestrus and pregnancy.

Animals↗