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Biomedical subjects

M Jeziorska

Publications and source records attributed to M Jeziorska.

At least 19 recordsLinked to original sources
PubMed2007

Contribution of VCAF-positive cells to neovascularization and calcification in atherosclerotic plaque development.

Calcification of the vessel wall is a regulated process with many similarities to osteogenesis. Progenitor cells may play a role in this process. Previously, we identified a novel gene, Vascular Calcification Associated Factor (VCAF), which was shown to be important in pericyte osteogenic differentiation. The aim of this study was to determine the localization and expression pattern of VCAF in human cells and tissues. Immunohistochemical analysis of seven atherosclerotic arteries confirmed VCAF protein expression within calcified lesions. In addition, individual VCAF-positive cells were detected within the intima and adventitia in areas where sporadic 3G5-positive pericytes were localized. Furthermore, VCAF-positive cells were identified in newly formed microvessels in association with CD34-positive/CD146-positive/c-kit-positive cells as well as in intact CD31-positive endothelium in internal mammary arteries. Western blot analysis confirmed the presence of VCAF (18 kD) in protein lysates extracted from human smooth muscle cells, endothelial cells, macrophages, and osteoblasts. In fracture callus samples from three patients, VCAF was detected in osteoblasts and microvessels. This study demonstrates the presence of VCAF in neovessels and raises the possibility that VCAF could be a new marker for vascular progenitor cells involved in a number of differentiation pathways. These data may have implications for the prevention or treatment of vascular disease.

Atherosclerosis↗
PubMed2006

Expression of osteonectin and matrix Gla protein in scleroderma patients with and without calcinosis.

OBJECTIVES: Our aim was to evaluate (i) whether the bone matrix proteins osteonectin and matrix gamma-carboxyglutamic acid protein (MGP) are up-regulated in skin biopsies from patients with systemic sclerosis (SSc) and (ii) whether there is differential expression between patients with and without dermal calcinosis, a distressing and debilitating complication of SSc. METHODS: Skin punch biopsies were taken from the forearms of 38 SSc patients with the limited cutaneous subtype of SSc [17 without calcinosis (lcSSc) and 21 with calcinosis (lcSScCal)] and from 11 healthy control subjects. Immunohistochemistry was performed with antibodies to osteonectin and MGP. Staining was assessed semiquantitatively in the microvascular endothelium and in dermal fibroblasts. The Kruskal-Wallis one-way ANOVA was used to compare the data between patient groups. RESULTS: Both lcSSc and lcSScCal groups showed a statistically significant increase in the percentage of microvessels with osteonectin-positive endothelial cells (EC) (especially the lcSScCal group), whereas lcSScCal alone showed an increase in the percentage of microvessels with MGP-positive EC when compared with controls. In both SSc groups, the percentage of osteonectin and MGP-stained fibroblasts was increased in the reticular dermis (for osteonectin this was more marked in the lcSScCal group). In the papillary dermis, the percentage of osteonectin-stained fibroblasts was increased in both SSc groups but the lcSScCal group alone had a higher percentage of MGP-stained fibroblasts. CONCLUSIONS: When compared with controls, protein expression of osteonectin and MGP was greater in SSc patients generally, and osteonectin expression was significantly higher in EC and fibroblasts of the lcSScCal patients than the lcSSc patients without calcinosis.

Adult↗
PubMed2004

Small fiber neuropathy in diabetes: clinical consequence and assessment.

Recent findings have shed new light on the role of peripheral nerves in the skin and have established a modern concept of cutaneous neurobiology. There is bidirectional rather than unidirectional (conveying information from the periphery) signaling between central and peripheral nerves and the endocrine and immune systems. This interaction is mediated principally by cutaneous small nerve fibers and will influence a variety of physiologic and pathophysiologic functions central to wound healing, which include cellular development, growth, differentiation, immunity, vasoregulation, and leukocyte recruitment. Thus, disease of the small fibers in diabetic patients is frequent and may have a considerable impact on the predisposition and subsequent wound-healing response to foot ulceration. The authors review the basic pathophysiology, clinical consequences, and current methods to evaluate somatic and autonomic nerve fiber dysfunction and damage.

Journal Article↗
PubMed2003

Vascular endothelial growth factors C and D and lymphangiogenesis in gastrointestinal tract malignancy.

Vascular endothelial growth factor-C (VEGF-C) and VEGF-D are members of the VEGF family of cytokines and have angiogenic and lymphangiogenic actions. In gastric adenocarcinoma, VEGF-C mRNA and tissue protein expression correlate with lymphatic invasion, lymph node metastasis and in some reports, venous invasion and reduced 5-year survival. Patients with gastric adenocarcinomas containing high levels of VEGF-C expression have significantly reduced 5-year survival rates, and VEGF-C expression is an independent prognostic risk factor for death. The role of VEGF-C in oesophageal squamous and colorectal cancer and VEGF-D in colorectal cancer is not clear, with conflicting reports in the published literature. In order to exploit potential therapeutic applications, further research is necessary to define the precise roles of these cytokines in health and disease.

Adenocarcinoma↗
PubMed2003

Clinical, biochemical, and immunohistochemical features of necrobiotic xanthogranulomatosis.

AIMS: To describe the clinical features of two patients with paraproteinaemia and necrobiotic xanthogranulomatosis together with detailed immunohistochemistry of the lesions in one. METHODS: The clinical history and results of biochemical investigations of the patients were retrieved from the files. Immunohistochemistry was used to investigate the expression of macrophage and mast cell markers, amyloid A and P, S-100 protein, and apolipoprotein AI and B in xanthogranulomatous skin lesions from patient 2. In addition, protein A-sepharose chromatography was used to separate serum from patient 2 and apolipoprotein B and the IgG paraprotein were measured in the fractions eluted. RESULTS: Monocytes/macrophages comprised the major cellular component of the lesion, and unusually for xanthomata, areas of collagen necrosis were also seen. Activated mast cells were present at the margins of macrophage clusters and adjacent to areas of collagen necrosis. Serum paraprotein was bound to low density lipoproteins as judged by protein A-sepharose chromatography, and was also located within macrophagic foam cells of the lesion on immunohistochemistry. CONCLUSIONS: These observations demonstrate many features similar to atherosclerosis including collagen necrosis and mast cell activation.

Aged↗
PubMed2002

Current understanding of cellular and molecular events in intervertebral disc degeneration: implications for therapy.

Until recently, material removed from the intervertebral disc (IVD) at surgery consisted either of 'loose bodies' from the centre of the IVD or discal tissue displaced (prolapsed) into the intervertebral root or spinal canals. This material is best regarded as a by-product of disc degeneration and therefore not representative of the disease process itself. Recent advances in surgical techniques, particularly anterior fusion, in which large segments of the anterior part of the IVD are excised with the anatomical relationships between different components intact, have generated material that can be investigated with modern molecular and cell biological techniques. This is an important area of study because degeneration of the lumbar IVDs is associated, perhaps causally, with low back pain, one of the most common and debilitating conditions in the West. 'Degeneration' carries implications of inevitable progression of wear-and-tear associated conditions. Modern research on human IVD tissue has shown that this is far from the case and that disruption of the micro-anatomy described as degeneration is an active process, regulated by locally produced molecules. The exciting consequence of this observation is the possibility of being able to inhibit or even reverse the processes of degeneration using targeted therapy.

Cytokines↗
PubMed2002

Nerve growth factor expression and innervation of the painful intervertebral disc.

Following a previous description of nociceptive nerve fibre growth into usually aneural inner parts of painful intervertebral disc (IVD), this study has investigated whether nociceptive nerve ingrowth into painful IVD is stimulated by local production of neurotrophins. Immunohistochemistry and in situ hybridization have been used to investigate expression of the candidate neurotrophin, nerve growth factor (NGF), and its high- and low-affinity receptors trk-A and p75, respectively, in painful IVD excised for the management of low back pain. IVD from patients with back pain were of two types: those that when examined by discography reproduced the patient symptoms (pain level IVD) and those that did not (non-pain level IVD). Microvascular blood vessels accompanied nerve fibres growing into pain level IVD and these expressed NGF. The adjacent nerves expressed the high-affinity NGF receptor trk-A. These vessels entered the normally avascular IVD through the discal end plates. NGF expression was not identified in non-pain level or control IVD. Some non-pain level IVD had vessels within them, which entered through the annulus fibrosus. These did not express NGF nor did nerves accompany them. These findings show that nociceptive nerve ingrowth into painful IVD is causally linked with NGF production by blood vessels growing into the IVD, from adjacent vertebral bodies.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Distribution and activation of eosinophils in inflammatory bowel disease using an improved immunohistochemical technique.

Eosinophils are a recognized feature of inflammatory bowel disease (IBD), but their tissue distribution and functional importance in Crohn's disease (CD) and ulcerative colitis (UC) remain obscure. This study describes an improved immunohistochemical protocol to identify eosinophils in full thickness bowel wall specimens of IBD (n=40) and their in situ relationships with the chemoattractants eotaxin and RANTES. Eosinophils were identified using immunohistochemistry with a combination of monoclonal antibodies (EG1+EG2+MBP), an ultrasensitive technique superior to other methodologies, and their tissue distributions were related to those for eotaxin, RANTES, mast cells and neutrophils. Increased numbers of eosinophils (up to 400 cells/mm(2)) were observed in active, fulminant inflammation in both CD and UC, this being related to the severity of inflammation and not the diagnosis of the two disorders. The chemoattractants eotaxin (CCL11) and RANTES (CCL5) were upregulated in IBD tissues showing eosinophilia. Neutrophils and mast cells were commonly associated with eosinophil accumulations. Eosinophil numbers and their in situ activation are increased in active rather than chronic IBD. The observations strongly suggest a pivotal role for the eosinophil and its potent mediators in many pathophysiological symptoms of CD and UC, where it represents the major proportion of all granulocytic cells in active inflammatory bowel disease.

Adult↗
PubMed2001

Transforming growth factor-betas and CD105 expression in calcification and bone formation in human atherosclerotic lesions.

OBJECTIVES: To investigate the expression and localisation of transforming growth factor betas (TGF beta s) and their receptor CD105 (endoglin) in relation to calcification and bone formation in atherosclerotic lesions of human carotid arteries. BACKGROUND: The TGF beta family regulates cellular growth, differentiation and angiogenesis and plays a key role in enchondral bone formation. CD105 is part of the TGF beta receptor complex preferentially expressed on endothelial cells (EC). METHODS: Immunohistochemical methods were used to determine the localisation of TGF beta isoforms 1, 2 and 3 and their spatial expression patterns in relation to calcification and bone formation in atherosclerotic lesions. Cellular sources of TGF beta s and CD105 were assessed using cell-type specific antibodies. RESULTS: There was marked variability in TGF beta expression in different cell types associated with calcification. Smooth muscle cells (SMC) in the atheroma cap showed higher levels of TGF beta 3 and 2 than 1, but in the deep musculoelastic intima there were higher levels of TGF beta 1 and alpha-actin. All three TGF beta isoforms were expressed in monocyte-macro-phages. Giant cells associated with calcifications showed intense staining for TGF beta 2. TGF beta 1 was most strongly expressed on matrix and cells associated with bone formation. CD105 expression on SMCs and monocyte-macrophages was lower on cells in close association with calcification. SMCs associated with bone formation expressed high levels of CD105. CONCLUSIONS: The different TGF beta isoforms exhibit distinct but overlapping patterns of expression, and support the hypothesis that they are involved in the process of calcification and bone formation in human atherosclerotic lesions. Lower expression of CD105 on cells associated with calcification may represent their state of lower responsiveness to TGF beta s.

Antigens, CD↗
PubMed1999

Local neovascularization and cellular composition within vulnerable regions of atherosclerotic plaques of human carotid arteries.

An improved immunohistochemical method has been used to assess neovascularization within the vulnerable 'shoulder' regions of atherosclerotic plaques from carotid arteries. A combination of monoclonal antibodies (CD31, CD34, +/- von Willebrand factor) was shown to be far more effective than conventional techniques in demonstrating extensive vascularizations within the 'shoulder' and cap regions of late-stage plaques. Such sites were shown to be microfocal, often appearing as a plexus of both large and small vessels which occupied a significant proportion of the 'shoulder' area. These regions of marked neovascularization were commonly associated with accumulations of macrophages, mast cells, and T-cells, indicative of local inflammatory reactions. The matrix components elastin and collagen type VI showed variable distributions which suggested extensive tissue remodelling, whereas collagen type IV was recognized as a basement membrane protein of most blood vessels, as well as being associated with 'stellate' smooth muscle cells. Evidence of local microvascular damage within the shoulder regions of some specimens was demonstrated by extravascular red blood cells, macrophages containing haemosiderin, and perivascular fibrin deposition. These local haemorrhages derived from microvessels beneath the lining of the arterial lumen are a further indication of how the microfocal vascularization of the plaque 'shoulder' might contribute to further complications of inflammation and plaque destabilization in late-stage disease.

Arteriosclerosis↗
PubMed1999

Neovascularization in early atherosclerotic lesions of human carotid arteries: its potential contribution to plaque development.

Neovascularization is a prominent feature of late-stage atherosclerotic lesions and their complications but is generally regarded as an insignificant, undetectable component of the earliest stages of plaque development, probably because of relatively poor histological techniques. Using an improved vascular staining procedure, we have examined the extent of neovascularization in the earliest plaque lesions. Combined monoclonal antibodies to CD31, CD34, and von Willebrand factor have provided an ultrasensitive technique with which to visualize blood vessels in early atherosclerotic lesions (n = 55) of human carotid arteries obtained through surgical procedures. Capillary-like microvessels were shown in very early atherosclerotic lesions (type II), where they were associated with the distribution of macrophages and a few immature mast cells. Neovascularization was more prominent in type III lesions with vessels of variable size, often providing a focus around which local accumulations of macrophages and apolipoproteins A-I and B were visualized. Thickened type III lesions usually showed an intricate network of microvessels, together with numerous mast cells. These studies have shown neovascularization as a prominent feature of early stages of atherosclerotic plaque development. Whereas distribution of apolipoproteins A-I and B were observed in the very earliest stages of the plaque intima, these lipids, together with macrophages, foam cells, and mast cells, were observed as perivascular accumulations in a proportion of type II and III lesions. Such findings indicate that neovascularization is an important feature of early plaque development and may provide an additional or alternative source of leukocyte and lipid accumulations relative to the arterial lumen.

Arteriosclerosis↗
PubMed1998

Calcification in atherosclerotic plaque of human carotid arteries: associations with mast cells and macrophages.

Calcification has been examined in 250 samples of atherosclerotic lesions (types II to VI) of human carotid arteries using von Kossa and haematoxylin staining. Early calcification described as 'stippling' was first noted in stage III specimens, with intermediate and solid calcifications becoming increasingly prominent within advanced plaques, especially stages Vb and VI. Although the relative frequencies of stippling, intermediate and large calcified deposits varied between plaques of the same stage, the prevalent sites of calcification were recognized as the deeper regions of the intima and the atheroma. Immunolocalization and histochemical techniques were used to identify the associations of mast cells (MCs), macrophages, smooth muscle cells (SMCs), and elastin with the different stages of calcification. Early, dispersed stippling was commonly associated with local accumulations of macrophages (HAM56 and CD68-positive), MCs and extracellular MC tryptase, the presence of immunoreactive elastin, but the relative absence of SMCs. Intermediate stages of calcification described as 'morula' deposits were also associated with local increases in the numbers of macrophages and MCs. Larger calcified deposits, even within the same plaque specimen, showed no regular pattern of cellular or elastin associations. However, in the vast majority of specimens, macrophages represented the predominant cell type associated with different phases of calcification. By contrast, the calcification less frequently observed in the media beneath advanced plaques was commonly associated with SMCs and elastin; only rarely were macrophages or MCs present. These studies are the first to demonstrate that macrophages, MCs, and extracellular tryptase frequently occupy micro-environmental loci showing the first stages of calcification within the atherosclerotic plaque; similar associations with more advanced mineral deposits are discussed in relation to plaque rupture.

Aged↗
PubMed1998

Evidence for in vivo mitosis by granule-containing mast cells from canine mastocytomas.

Mast cell accumulations are generally considered to arise almost exclusively from the recruitment of non-granulated, bone-marrow-derived, precursor cells, with the stem cell factor (SCF) reported to play a crucial role in the growth, development and maturation of granulated mast cells within specific tissue sites. In this study dog mastocytoma specimens have been examined by both immunohistochemical and ultrastructural techniques, to demonstrate that fully granulated mast cells are capable of mitotic activity. Observations showing the formation of mitotic spindles, chromosome separation and cytokinesis all support the concept that granulated mast cells are capable of proliferative activity. The ability of mature granulated mast cells to replicate provides an alternative process for local increases in mast cell numbers, at least in canine mast cell tumours. Such observations suggest the possibility that normal or neoplastic human mast cells, fully granulated, have the potential to proliferate in specific tissue sites.

Animals↗
PubMed1998

Observations on bone formation and remodelling in advanced atherosclerotic lesions of human carotid arteries.

Immunolocalisation and histochemical techniques were used to examine mineralised bone deposits within late stage atherosclerotic plaques of human carotid arteries. These specimens showed characteristic features of osteogenesis. Large calcifications were often observed in close association with or integrated within mineralised bone. Smooth muscle cells (alpha-actin positive) were often located around osteoid-like matrix, together with focal accumulations of macrophages (CD68 and HAM56 positive). Local accumulations of mast cells (tryptase positive) were consistently observed in close association with the bone. Multinucleated giant cells in close apposition with mineralised bone demonstrated typical osteoclastic morphology, and were positively stained for acid phosphatase and the macrophage marker CD68. Thus, all the normal features of bone formation and resorption were observed in this microcosm of osteogenesis within atherosclerotic plaque; the term 'osteosome' seems appropriate for the structure. These osteosomes have numerous advantages for experimental studies of the various osteogenic factors responsible for bone metabolism, especially following short-term tissue culture. This ex vivo technique was used to demonstrate the distribution and the multiple cellular sources of bone morphogenetic protein 6.

Acid Phosphatase↗
PubMed1997

Mast cell distribution, activation, and phenotype in atherosclerotic lesions of human carotid arteries.

Immunohistochemical staining for mast cell tryptase and chymase was used to examine the distribution, activation, and tryptase/chymase phenotype of mast cells (MCs) in 250 samples of atherosclerotic lesions (type I to VI) of human carotid arteries. Dual immunolocalization and histochemical techniques were used to identify the associations of MCs with macrophages, smooth muscle cells, and extracellular matrix components. Whereas normal carotid arteries contained very few MCs within the intima, atherosclerotic lesions showed increased MC numbers with variable focal accumulations. MCs were identifiable from the earliest stages of atherosclerosis, and especially at the shoulder regions of the fully formed atheroma. They were observed in close association with macrophages (HAM56 positive) and extracellular lipid, as well as at sites of foam cell formation. MCs and diffuse tryptase staining were also evident within sites of new calcification and around small calcified deposits. Extensive MC activation/degranulation, as judged by diffuse extracellular tryptase staining, was a common feature of the advanced atherosclerotic plaques complicated by fissure, haemorrhage, and thrombus formation. Moreover, such sites of extracellular MC tryptase were often associated with localized oedema and disruption of the stromal matrix. MCs which contained both tryptase and chymase (the MCTC phenotype) represented approximately 80-95 per cent of all MCs. These studies are the first to demonstrate significant numbers and focal accumulations of MCs in all developmental stages of atherosclerotic carotid arteries. Since MCs contain or express a variety of potent mediators, their release could profoundly influence the development and pathological complications of atherosclerotic plaques.

Aged↗
PubMed1997

Mast cells in cervical ripening--an immunohistochemical and biomechanical study in rats.

Cervical ripening purportedly involves different cell types and mediators normally associated with inflammatory reactions. The purpose of the present study was to determine the presence of mast cells in rat cervices during spontaneous and antigestagen induced ripening and to test whether a mast cell stabilizer was able to inhibit the antigestagen induced cervical ripening. Immunohistochemical examinations demonstrated an increased number of mast cells in pregnant and intrapartum rats. Furthermore, mast cell degranulation was found to be prominent after antigestagen treatment. The degranulation was completely abolished by co-treatment with the mast cell stabilizer. Biomechanical analysis showed that the mast cell stabilizer also inhibited the antigestagen induced cervical ripening to some extent. Thus, it is concluded that mast cell stabilizers might constitute a new approach in the treatment of preterm cervical ripening.

Animals↗
PubMed1996

Evidence against a significant role for mast cells in blastocyst implantation in the rat and mouse.

Rats were treated with the highly potent stabilizer of mast cells, FPL 55618, before and during the first seven days of pregnancy to establish whether stabilization of mast cells resulted in impaired blastocyst implantation. There was no significant reduction in either the number of ovulations or the number of implantation sites in treated rats compared with controls; 11 of 15 treated rats were pregnant compared with 5 of 6 control rats. The distribution of mast cells was examined in uterine tissues, implantation sites and interimplantation sites in both rats and mice using highly sensitive immunohistochemical techniques. Virtually all of the mast cells in rat uterine tissue stained for rat mast cell protease-I (RMCP-I; connective tissue type), whereas few stained for RMCP-II (mucosal type). Most of the mast cells were present in the myometrium with very sparse distribution in the endometrium and there were no differences in numbers of mast cells between implantation and inter-implantation sites on Day 7 of pregnancy. In tissue sections of mouse uteri sampled from Day 1 to Day 8 of pregnancy there were virtually no mast cells in the endometrium or deciduum adjacent to implantation sites. Mouse uterine mast cells also stained predominantly for the connective tissue-type mast cell protease MMCP-4, the murine equivalent of RMCP-I. Thus, mast cells and their products appear to play little, if any, role in blastocyst implantation in murid rodents. Since mast cells are a prominent feature of human endometrium, this study emphasizes the important consideration of species differences when choosing animal models for implantation studies.

Animals↗