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Biomedical subjects

M Vered

Publications and source records attributed to M Vered.

At least 19 recordsLinked to original sources
PubMed2006

Immunohistochemical expression of glucocorticoid and calcitonin receptors as a tool for selecting therapeutic approach in central giant cell granuloma of the jawbones.

Aggressive cases of central giant cell granuloma (CGCG) have been arbitrarily treated with steroids and calcitonin. The aim of this study was to develop a practical tool, based on the relative percentage of positively stained cells for glucocorticoid and/or calcitonin receptors, for selecting the appropriate therapeutic agents to treat CGCG. Forty-one formalin-fixed, paraffin-embedded blocks of CGCG were immunohistochemically stained for glucocorticoid and calcitonin receptors. Percentage of positive lesional mononuclear and giant cells was estimated for each case. Intense staining was considered as staining 50% or more of the cells. Correlations among staining scores were analysed by Spearman's test. All cases stained for glucocorticoid receptor. Heterogeneity among cases showed as intense staining in both cell types (21 lesions), in only one cell type (13 lesions) and weakly in both cell types (7 lesions). Only 23 cases demonstrated staining for calcitonin receptor, of which 15 stained intensely in both cell types and 7 in only one cell type. Among staining scores of both receptors, no significant statistical correlation was found (P>0.05). It can therefore be suggested that the relative percentage of immunohistochemically stained mononuclear and giant cells for glucocorticoid and/or calcitonin receptors can serve as a reliable and practical tool for selecting the appropriate therapeutic agent to treat CGCG. The clinical application of this method should be assessed in well controlled clinical studies, especially in cases of aggressive lesions, before initiating and during therapeutic treatment.

Adolescent↗
PubMed2006

Giant cell granuloma of the jawbones--a proliferative vascular lesion? Immunohistochemical study with vascular endothelial growth factor and basic fibroblast growth factor.

AIM: To estimate the angiogenic activity in central giant cell granuloma (CGCG) by immunohistochemical stains for vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). VEGF and bFGF immunoreactivity of the lesional mononuclear (MC) and giant (GC) cells was also investigated. METHOD: The study consisted of 41 cases of CGCG. Vascularity was quantified by microvascular volume (MVV) as determined by point counting. In five cases of CGCG, regions at the surrounding border, which demonstrated reactive vascular-rich inflammatory areas, served as control. Immunoreactivity of the MC and GC was assessed as the percentage of VEGF- and bFGF-positive cells from the total number of the respective cell type. RESULTS: Within CGCG lesions the extent of angiogenesis was low; MVV did not exceed 5% for either VEGF (88% of lesions) or bFGF (78% of lesions). The mean MVV of VEGF- and bFGF-positive blood vessels was 2.9% +/- 2.4% and 3.46% +/- 2.35%, respectively, significantly lower than in the control areas (27.5% +/- 7.3% and 28.08% +/- 5.5%, respectively) (P = 0.043). VEGF-positive and bFGF-positive MC and GC were found in nearly all lesions and in less than half of the lesions, respectively. CONCLUSION: The low mean MVV of VEGF- and bFGF-positive blood vessels implies low angiogenic activity, which does not support the designation of CGCG as a true proliferative vascular lesion. MC and GC immunoreactivity for the angiogenic factors is assumed to play an important role in the osteoclastogenesis process, thus contributing to additional growth of the CGCG lesions.

Adolescent↗
PubMed2004

Treatment modalities for chemo--and radiotherapy-induced oral mucositis--critical analysis and practical guidelines.

Oral mucositis (OM), an inevitable side effect of almost all anti-cancer treatments, affects the patient's physiological functions and their psychological well being. In spite of numerous treatment modalities for this condition, there is still a lack of evidence-based clinical trials that can provide a single efficient pharmacologic agent or intervention for either prevention or treatment of OM. This study analyses and summarizes some of the more "accepted" modalities for treatment of OM. It is recommended that these modalities rely on simple, convenient and innocuous interventions, which should be adjusted for each individual complaint. Well-designed, controlled and standardized studies are necessary to validate effectiveness of available, as well as newly developed interventions for OM.

Anti-Infective Agents, Local↗
PubMed2001

Focal lymphocytic infiltration in aging human palatal salivary glands: a comparative study with labial salivary glands.

Investigation of age-related prevalence of various types of focal lymphocytic infiltration (FLI) and degrees of histomorphologic changes was conducted on 120 biopsies of palatal and labial salivary glands (PSG and LSG, respectively) obtained from autopsy subjects free of salivary gland tumors/diseases. Biopsies were divided into young (<30 years, n=30), adult (30-60 years, n=45) and old (>60 years, n=45) age groups. A modified Chisholm & Mason grading system was used to record grades of FLI and a modified Greenspan et al. system was used to evaluate the severity of histomorphologic changes. The prevalence of FLI in PSG increased significantly from 10% in the young group to 46.6% in the old group (P=0.0012). No significant changes were found with aging in LSG. FLI was significantly more prevalent in the adult and old age groups in PSG as compared with LSG (P=0.015 and P=0.003, respectively). Both glands demonstrated significant histomorphologic changes among age groups (p<0.0001); however, these changes were significantly less common in the old age group in PSG as compared to LSG (P=0.003). In cases showing severe histomorphologic changes, FLI was not present. Therefore, FLI should not be considered as part of the deteriorating histomorphologic changes that are usually encountered in salivary glands with aging. The immunologic profile of these infiltrates should be further clarified to understand their role, both in physiologic and pathologic conditions.

Adult↗
PubMed2000

Age-related histomorphometric changes in labial salivary glands with special reference to the acinar component.

PURPOSE: To evaluate histomorphometric age-related changes in labial salivary glands (LSG) of healthy subjects, with special reference to the mucous and seromucous acini. METHOD: Investigation of age-related histomorphometric changes was conducted on 120 samples of LSG obtained from autopsy subjects free of salivary gland tumors/diseases. Samples were divided into young (< 30 years, n = 30), adult (30-60 years, n = 45) and old (> 60 years, n = 45) age groups. Measurements were performed on hematoxylin and eosin stained slides. Parenchymal components included acini and ducts. The acinar component was presently analyzed separately in respect to mucous acinar cells and seromucous acinar cells. Mucous acinar cells presented pale eosinophilic cytoplasm, while that of the seromucous was darker and basophilic. Stromal components included connective tissue, blood and lymphatic vessels, inflammatory infiltrate and adipose tissue. The mean volume fraction (V(v)) of all components in each age group was calculated. Statistical analysis was performed by one-way ANOVA and Tamhane tests. RESULTS: The mean V(v) of the seromucous acinar cells decreased by 49.3% (p < 0.0001) and that of the mucous acinar cells decreased only by 28.5% (p = 0.0001). Changes in the ducts were statistically non-significant (p = 0.312). Of the stromal components, the mean V(v) of the adipose tissue showed the highest increase, 2768% (p < 0.0001) followed by the inflammatory infiltrate, 512% (p < 0.0001). CONCLUSIONS: The marked decrease in the V(v) of seromucous acinar cells accompanied by a lower decrease in the V(v) of mucous acinar cells may explain age-related changes in LSG secretion. These findings could bear important implications regarding functional age-related changes of these glands.

Adult↗
PubMed2000

Aging of human palatal salivary glands: a histomorphometric study.

The aim of the present study was to examine age-related changes in the parenchymal and stromal components of palatal salivary glands of healthy subjects. Palatal salivary gland biopsies were obtained from 120 autopsies and were divided into young, adult, and old age groups. Histomorphometric measurements were performed on hematoxylin and eosin (H&E) stained slides. Parenchymal components included acini and ducts, and stromal components included connective tissue, blood and lymphatic vessels, inflammatory infiltrate, and adipose tissue. The mean volume fraction of each component in each age group was calculated. Statistical analysis was performed by one-way ANOVA and Tamhane tests. The mean volume fraction of the acinar component demonstrated a significant age-related decrease of 48% (P < 0.001). The mean volume fractions of the ducts and of all the stromal components demonstrated a significant age-related increase (P < 0. 001). The inflammatory infiltrate component had the highest increase with aging (1471%), followed by the ducts (177%), blood and lymphatic vessels (138%), adipose tissue (130%), and connective tissue (60%). These age-related changes, the first to be reported in palatal salivary glands from healthy subjects, are different from those described in the labial salivary glands, especially in regard to the significant increase in the parenchymal ductal component, as well as in the stromal inflammatory infiltrate and adipose tissue components. It can be suggested that these changes could have important implications regarding the age-related function of these glands.

Adolescent↗
PubMed1998

Lingual osteoma: a debatable entity.

PURPOSE: This article analyzes osseous lesions in the tongue with regard to the clinical and histologic features and discusses the pathogenesis and terminology of these lesions. MATERIALS AND METHODS: Thirty-eight cases of lingual osseous lesions were retrieved from the English language literature, and two new cases were added. RESULTS: The lesions had a female predilection, with a female-to-male ratio of 2.3:1. Mean age of the patients at time of diagnosis was 31.4 years. The lesions were located in the posterior third of the dorsum of the tongue in 67.5% of the cases, in the lateral margins in 25%, and in the mid-third of the tongue in 7.5%. Size ranged from 0.5 to 5.0 cm. Duration of the lesions ranged from several months to 50 years. In eight cases, there was information that the lesions had increased in size. Histologically, the lesions appeared a well-circumscribed mass of vital bone under the surface epithelium. The two new cases, when examined by polarized light, showed a mixture of woven and mature bone. CONCLUSION: The osseous lesions of the tongue represent a heterogeneous group of lesions in which some may represent a developmental malformation, and others may be a reactive lesion after trauma or irritation. Some lesions behave as true neoplasms and others as choristomas. It is suggested that the descriptive term "osseous tumorlike lesion of the tongue" may be more appropriate for this group.

Adult↗
PubMed1998

An immunohistochemical study of p53 and PCNA in inflammatory papillary hyperplasia of the palate: a dilemma of interpretation.

OBJECTIVE: Inflammatory papillary hyperplasia of the palate (IPHP) or the granular type of denture stomatitis, is a non-neoplastic lesion characterized histologically by a significant epithelial hyperplasia and inflammatory infiltrate usually caused by trauma and Candida infection. p53 and proliferative cell nuclear antigen (PCNA) are cell-cycle regulators, that when overexpressed, are considered by many investigators as markers of malignant transformation. The objective of this study was to investigate the immunodetection of p53 and PCNA in IPHP, and to correlate these results with the degree of epithelial hyperplasia and inflammatory infiltrate. MATERIALS AND METHODS: In 12 cases diagnosed clinically as IPHP, Candida was cultured from the denture base and the palatal mucosa. Lesions were biopsied and stained with H&E for histomorphometric analysis of the epithelial width and inflammatory infiltrate. PAS and Gram stains were used for screening of Candida. Sections were immunostained with DO-7 for p53 and PC-10 for PCNA. Fifteen palatal biopsies obtained from autopsies of edentulous subjects with normal palatal mucosa served as controls. RESULTS: All cultures of swabs from both the palatal mucosa and denture base were positive for Candida. Candidal hyphae could not be identified in PAS stained sections. Small foci of Gram-positive organisms were found in two cases of IPHP. Epithelial width and inflammation were significantly higher in IPHP than in controls (P < 0.001). A three-fold increase in positively stained cells for p53 and a two-fold increase in positively stained cells for PCNA were seen in IPHP compared with controls (P < 0.001). CONCLUSIONS: Although a significant increase in the immunodetection of p53 and PCNA may indicate a malignant potential, IPHP has never been reported to undergo malignant transformation nor is it associated with cytologic signs of dysplasia. The increase in the epithelial width and inflammation degree is probably associated with the colonization of the denture bases with Candida organisms. The increased detection of p53 and PCNA can be a secondary effect of cytokines originating from both the inflammatory cells and the keratinocytes. Thus, immunodetection of p53 and PCNA by current immunohistochemical methods on archival tissues is neither specific nor sensitive enough to be used as indicators for malignant potential in the absence of cytological dysplastic changes or genetic proof of mutated cell cycle genes.

Aged↗
PubMed1994

Anti-ischemia activity of HU-211, a non-psychotropic synthetic cannabinoid.

The novel tricyclic-terpenoid type cannabinoid, HU-211, was tested in gerbils and rats for protection against the effects of cerebral ischemia. Our transient ischemic models in gerbils and rats are based on the protection afforded against the lethal effects of global ischemia. HU-211 gave over 30% protection, by i.v. administration. The optimal dose ranges of HU-211 were between 5 and 10 mg/kg i.v. In gerbils we used a transient ischemia model induced by occlusion (10 min) of the bilateral common carotid arteries (BCCA). HU-211, 8 mg/kg i.v., gave a significantly (p < or = 0.05) better in vivo performed than a control group over three days following ischemia. Histology performed in gerbil model also resulted in significantly (p < 0.001) diminished degeneration area of CA1 in the hippocampus after treatment of HU-211. In the rat model, after four vessel occlusion (4VO) (20 min), HU-211 treatment significantly (p < 0.01) improved neurobehavior scoring. These results show that the new synthetic cannabinoid can protect against hippocampal neuron damage due to selective brain injury induced by cerebral global ischemia in gerbils or rats.

Animals↗
PubMed1994

Loteprednol etabonate: comparison with other steroids in two models of intraocular inflammation.

Loteprednol etabonate (LE) is a novel steroid with a low tendency to raise IOP. It is metabolized in the eye to an inactive metabolite. The current study was undertaken to assess the intra-ocular anti-inflammatory activity of LE in two models of experimental uveitis in rabbits. In the endotoxin induced rabbit model, LE was effective at reducing measures of inflammation, but less so that either fluorometholone (FML) or dexamethasone. In the Freunds adjuvant chronic uveitis model, FML was also very effective with LE and dexamethasone showing similar activity. The data demonstrate that LE is effective at reducing intra-ocular inflammation.

Androstadienes↗
PubMed1990

Inhibition of the activity of human leukocyte elastase by lipids particularly oleic acid and retinoic acid.

The effect of various natural hydrophobic lipids on the in vitro and in vivo activity of human leukocyte elastase has been examined. In vitro studies using 2 different substrates indicated that fatty acids inhibit human leukocyte elastase activity, with maximum inhibition observed with oleic acid. Triolein, cholesterol, and beta-carotene caused little inhibition. The presence of a carboxyl group appears important since retinoic acid but not retinol also inhibited activity. In vivo studies of an emphysema model in mice indicated that intrapulmonary instillation of oleic or retinoic acid reduced lung injury caused by human leukocyte elastase. The possibility of using these compounds to diminish elastolytic damage in emphysema is raised.

Animals↗
PubMed1988

Inhibition of human neutrophil elastase by bacterial polyanions.

We previously demonstrated that pneumococcal extracts contain a highly specific inhibitor of human neutrophil elastase (HNE). We now show that the active inhibitor in these extracts is a high-molecular-weight, heat-stable substance that appears to be RNA, since inhibitory activity of pneumococcal extracts is decreased by incubation with ribonuclease but not by incubation with deoxyribonuclease or proteinase K. Moreover, metabolically labeled ([3H]uridine) pneumococcal RNA, isolated by phenol extraction followed by ethanol precipitation, strongly inhibits HNE. Pneumococcal capsular polysaccharide, although polyanionic, is only weakly inhibitory toward HNE and is not a major source of elastase-inhibitory activity in pneumococcal extracts. On the other hand, the capsule of Haemophilus influenzae type b contains polyribosylribitol phosphate. This highly charged polyanion possesses HNE-inhibitory activity, but only under special circumstances to be discussed below. Pneumococci (type I, type II smooth, type II rough) and H. influenzae (type b) all release HNE-inhibitory activity into their culture medium during growth. By contrast, Klebsiella pneumoniae and Staphylococcus aureus release little (if any) stable HNE-inhibitory activity during growth. We propose that some bacterial pneumonias may spare host tissue because polyanions released by the invading microorganisms (e.g. RNA from autolysing pneumococci) inhibit elastase released from inflammatory neutrophils and thereby modulate accompanying tissue proteolysis. Pneumonias caused by microorganisms that do not release stable polyanionic inhibitors of HNE (e.g., Staphylococcus and Klebsiella) may be correspondingly more injurious to the lung.

Haemophilus influenzae↗
PubMed1988

Inhibition of human neutrophil elastase by polyguanylic acid and other synthetic RNA homopolymers.

Human neutrophils contain large amounts of a neutral serine protease, human neutrophil elastase (HNE), which has been implicated as a mediator of acute and chronic lung injury. We found that this enzyme is effectively inhibited, at physiological ionic strength, by several synthetic non-base-paired polyribonucleotides. Among the most active of these is polyguanylic acid (poly G). Inhibitory activity is greatest with high-molecular-weight poly G fractions, but poly G fractions even as low as 60K Mr (app) are effective. Both amidolysis of synthetic elastase substrates, such as succinyl-ala-ala-ala-p-nitroanilide, and proteolysis of elastin are blocked. Poly G inhibits elastin proteolysis even when subsequently added to mixtures of elastin and HNE that have first been preincubated together for 10 min. Under these conditions, polyribosylribitol phosphate, a polyanion derived from Haemophilus influenzae capsular polysaccharide, is not inhibitory. Complex formation between HNE and poly G is dependent on ionic rather than covalent interactions, since it is blocked by 0.6 M NaCl but not by inactivation of the enzyme's catalytic-site serine residue with diisopropylfluorophosphate. However, nonspecific ionic interactions alone cannot explain complex formation, since pancreatic elastase and cathepsin G, an even more basic serine protease from human neutrophils, do not form complexes with poly G, even at low ionic strength. Moreover, in the presence of the amphiphiles taurocholic acid and glycocholic acid, HNE is much less effectively blocked by poly G. Peptide chloromethyl ketone-inactivate HNE (which has its extended substrate-binding pocket occupied by the peptidyl inactivator) also fails to form complexes with poly G. These results indicate that HNE may utilize both hydrophobic and ionic binding sites to couple with poly G, and suggest that these sites may be close to or within the extended substrate-binding pocket of the enzyme.

Amino Acid Chloromethyl Ketones↗
PubMed1986

Partial amino acid sequence of porcine elastase II. Active site and the activation peptide regions.

The partial amino acid sequence of porcine elastase II, isolated from crude trypsin Type II, was determined. The enzyme consists of two polypeptide chains, a light chain composed of 11 residues, and a heavy chain (Mr = 23 500) with four intrachain disulfide bridges; the two chains are held together by one interchain disulfide bond. Elastase II was fragmented into several peptides by chemical cleavages with CNBr at the two methionine residues, 99 and 180 (chymotrypsinogen numbering), and with hydroxylamine at the peptide bond following DIP-Ser195. About 50% of the sequence was determined and the positions of 120 amino acids were located, including the light chain residues and most of the active site residues. The partial sequence shows 64% difference between porcine elastase II and elastase I and only 26% difference between porcine elastase II and bovine chymotrypsin B.

Amino Acid Sequence↗
PubMed1985

Digestion of elastin by porcine pancreatic elastase I and elastase II.

Elastin was fully solubilized by digestion with elastase I or elastase II. Each digest was separated into high-molecular weight and low-molecular weight fractions that were characterized by the correspondence to their amino acid content, N-terminal sequence and C-terminal amino acids. It was found that although the relative amount of amino acids in the low-molecular weight fraction obtained by digestion with elastase I was lower than in digestion with elastase II, no major difference in the type of bonds cleaved in the low- or high-molecular weight fractions of each digest could be seen. There is, however, a remarkable difference in the type of bond cleaved by the two enzymes. While elastase I cleaves mostly Ala-Ala and also Ala-Gly bonds, elastase II hydrolyzes Leu-Ala, Leu-Gly, Phe-Ala, Phe-Gly and Tyr-Ala, Tyr-Gly bonds. Theoretical calculations led us to suggest both digests are composed of cross-linked peptides that vary not only in the molecular size but also in the number of cross-links found in peptides of the same size.

Amino Acid Sequence↗
PubMed1985

Subcellular localization and further characterization of a new elastase inhibitor from pneumococci.

Streptococcus pneumoniae contains an inhibitor of human neutrophil elastase. The agent does not inhibit other proteases, including neutrophil cathepsin G and pancreatic elastase. It is active in the presence of insoluble elastin as well as synthetic elastase substrates. The inhibitor is present in the pneumococcal cell membrane. [125I]elastase binding studies and inhibition experiments with intact bacterial autoplasts suggest that this agent has its elastase-binding site(s) exposed on the outside of the bacterial cell membrane. Native and randomized membrane vesicles also show equal inhibitory activity. Active inhibitor can be solubilized from pneumococcal membranes by treatment with a dipolar ionic detergent and can then be reconstituted, in active form, within artificial liposomes. Complex formation between the neutrophil elastase inhibitor and neutrophil elastase may involve noncovalent associations. Although elastase containing a covalently bound substrate analog no longer binds the pneumococcal inhibitor, the present study shows that complex formation is nevertheless independent of neutrophil elastase catalytic activity. Specific inhibitor activity and inhibitor release during bile salt-stimulated autolysis are greater in a nonnecrotizing pneumococcal strain (type I) than they are in a necrotizing strain (type III) or in Klebsiella pneumoniae. These results may help explain the frequent resolution of some pneumococcal pneumonias, despite the presence in the early pneumonic exudate of many neutrophils containing an elastolytic protease capable of injuring lung connective tissue.

Autolysis↗