Biomedical subjects

Zygmunt Mackiewicz

Publications and source records attributed to Zygmunt Mackiewicz.

4 recordsLinked to original sources

PubMed2006

EMMPRIN and MMP-1 in keratoconus.

PURPOSE: This study was conducted to determine the eventual presence and activity of EMMPRIN (extracellular matrix metalloproteinase inducer CD147) and interstitial collagenase MMP-1 in the cornea of keratoconus patients and their eventual interrelationship. MMP-1 was chosen because it is able to degrade fibrillar corneal collagens type I and III and might therefore play a role in stromal thinning in keratoconus. METHODS: Immunohistochemical labeling of EMMPRIN and MMP-1 in relation to histopathological changes in 5 keratoconus patients and 5 matched healthy controls was investigated. RESULTS: Relatively strong EMMPRIN expression was found in normal corneal epithelial cells, but moderate expression was also found in stroma. In keratoconus, EMMPRIN was found in all layers of cornea, especially in histopathologically altered areas. In normal cornea, MMP-1 staining was weak and restricted to epithelial cells. In keratoconus, MMP-1 expression was slightly augmented in epithelial cells and also appeared locally in a scattered manner in the stroma. The distribution of MMP-1 did not totally overlap with that of histologically apparent corneal damage and EMMPRIN expression. CONCLUSIONS: Both EMMPRIN and MMP-1 are upregulated in keratoconus, but MMP-1 may not be the only tissue destructive MMP upregulated by EMMPRIN as only EMMPRIN expression correlated topologically very well with corneal damage.

Basigin↗

PubMed2006

Collagenolytic proteinases in keratoconus.

PURPOSE: To study the proteolytic phenomena contributing to the pathogenesis of keratoconus, corneal enzymes with potential to cleave fibrillar collagen were studied. METHODS: Immunohistochemical labeling was undertaken of conventional and novel mammalian collagenases (MMP-1, -2, -8, -13, and -14) of the matrix metalloproteinase (MMP) family and other collagenolytic proteinases of the serine (human trypsin-2) and cysteine (cathepsin K) endoproteinase families. The results were analyzed using a semiquantitative scoring system. RESULTS: Labeling of MMP-8 was moderate in healthy controls, but weak in keratoconus. Moderate MMP-2 and weak MMP-14 expressions were similar in controls and keratoconus. MMP-1 was slightly overexpressed in keratoconus. In contrast, MMP-13 was weak in controls compared to moderate in keratoconus and human trypsin-2 and cathepsin K were moderate in controls and strong in keratoconus. CONCLUSIONS: The collagenolytic milieu of human cornea is more complex than expected. Mesenchymal isoform of MMP-8 (ie, collagenase-2) participates in normal tissue remodeling, which may be impaired in keratoconus. MMP-2 (gelatinase A with interstitial collagenase activity) and MMP-14 (membrane-type MMP type I with collagenolytic potential) seem to be constitutively expressed and probably play a role in normal corneal remodeling. The most prominent changes in keratoconic cornea were observed in collagenase MMP-13 (ie, collagenase-3), and particularly, in cathepsin K and human trypsin-2, which were strongly expressed in keratoconus suggesting a role in intra- and extracellular pathological collagen destruction, respectively. This may contribute to stromal thinning characteristic for keratoconus.

Cathepsin K↗

PubMed2006

Age-related changes in myocardial nerve and collagen networks of the auricle of the right atrium.

OBJECTIVE: The objective of this study was to analyse age-related changes in human myocardial nerve plexuses and collagen networks of the auricle of the right atrium in subjects in whom no cardiac diseases or pathology had been diagnosed. METHODS AND RESULTS: Morphometric analysis of acetylcholinesterase (AChE)-stained nerve plexuses and picrosirius-stained cardiac collagen networks from 17 persons of both genders aged 20-94 years was performed using video microscopy and a digital video camera. It was found that with age linear regression of nerve plexuses occurred.Atrial collagen content increases lifelong. CONCLUSION: Aging of human atrial myocardium is accompanied by a decrease of nerve plexuses and an increase in fibrosis.

Acetylcholinesterase↗

PubMed2003

Disease-associated increased HIF-1, alphavbeta3 integrin, and Flt-1 do not suffice to compensate the damage-inducing loss of blood vessels in inflammatory myopathies.

OBJECTIVE: To analyze the microvascular network in skeletal muscle biopsies from patients with dermatomyositis (DM) and systemic sclerosis (SSc) compared to polymyositis (PM) and systemic lupus erythematosus (SLE), and non-inflammatory myopathies, and to clarify whether reparative angiogenesis-related factors are expressed in parallel to blood vessel damage. METHODS: Immunohistochemical staining of muscle biopsies (10 DM, 10 SSc, 10 PM, 10 SLE, and 10 non-inflammatory myopathies) with antibodies against von Willebrand factor (vWF), hypoxia-inducible factor-1beta (HIF-1beta), beta3 integrin subunit, and vascular endothelial growth factor receptor-1 (VEGFR-1). The TechMate staining robot and biotin-streptavidin protocol were used. RESULTS: DM and SSc muscles were characterized by endothelial damage and reduction of blood vessel network. Expression of angiogenesis-related factors (HIF-1beta, beta3, VEGFR-1) was also found in the same biopsies. In contrast, in PM and SLE muscles, vascular networks were apparently not affected and angiogenic stimuli were less expressed if at all. CONCLUSIONS: This work demonstrates that in inflamed muscles hypoxia/ischemia induces increased expression of angiogenic factors, yet their impact is insufficient to repair disease-associated reduction of the capillary network. This leads to questions considering the usefulness of angiogenic factors in the treatment of ischemic inflammatory myopathies in DM and SSc.

Biomarkers↗