Annexins are peripheral membrane-binding proteins implicated in a number of membrane-related events (for a review see refs. 1, 2). Of particular interest within this family is annexin A2, since it can exist in two forms possibly showing... more
Annexins are peripheral membrane-binding proteins implicated in a number of membrane-related events (for a review see refs. 1, 2). Of particular interest within this family is annexin A2, since it can exist in two forms possibly showing different modes of membrane interaction, the ...
The coronavirus outbreak in recent times has created a terrific pandemic situation in the universe. We aim to identify the specific domain in the viral particle responsible for binding into the host cell and for finding any anti-viral... more
The coronavirus outbreak in recent times has created a terrific pandemic situation in the universe. We aim to identify the specific domain in the viral particle responsible for binding into the host cell and for finding any anti-viral drug that could inhibit the binding interaction. Using pharmacophore-based drug modelling for drug molecule that can inhibit the spike protein interaction is targeted. Spike protein of a viral body (SARS-CoV-2) represents a structure that acts as the ligand that binds with the host, made up of several repeats of Beta sheets acts as the substrate-binding domain part. The anti-viral drug or the antibody inhibit the interaction between the spike and the receptor, are predicted via receptor-ligand interaction of the desired or predictable drug molecule. Common and trusted anti-viral strategies directed to S-protein consist of mitigation of host recognition by acting on S1-RBD (Spike Protein Receptor Binding Domain) coupled with inhibition of fusion process by acting at the level of S2 sub-unit has been explored. Drugs like Favipiravir and Barcitinib are in use to reduce viral entry in the host cells, along with several developing vaccines.
This study was done to arrive at a fast and reliable protocol for assessment of fractional volumes of immunohistochemically stained dendritic cells in lymph nodes. Twenty axillary lymph nodes of patients with locally advanced breast... more
This study was done to arrive at a fast and reliable protocol for assessment of fractional volumes of immunohistochemically stained dendritic cells in lymph nodes. Twenty axillary lymph nodes of patients with locally advanced breast cancer were immuno‐histochemically stained with an S100 antibody. Fractional volumes of dendritic cells were assessed by stereology based quantitative immunohistochemistry using an interactive video overlay system including an automated microscope. The gold standard percentage of dendritic cells was the fractional volume of S100 stained cells in 500 fields systematically spread over the whole lymph node. Then, in a computer simulation, different sample sizes (1–200 fields of vision) were tested and the coefficient of variation (CV) for each sample size was calculated. The CV dropped with increasing sample size. A sample size of 100 fields of vision appeared to be optimal. Intra‐ and interobserver reproducibility appeared to be good (correlation coefficie...
Some authors suggest common origin of gastrointestinal stromal tumors from stem cells, which may show diverse differentiation. There are reports in which cells morphologically identical to the interstitial cells of Cajal are found in deep... more
Some authors suggest common origin of gastrointestinal stromal tumors from stem cells, which may show diverse differentiation. There are reports in which cells morphologically identical to the interstitial cells of Cajal are found in deep leiomyomas. The aim of this study was to demonstrate CD117 positive cells in superficial gastrointestinal (GI) leiomyomas and to find other cells that would suggest diverse differentiation in histologically typical leiomyoma. We analyzed 8 cases of superficial leiomyomas and one deep leiomyoma, received in our institutions as endoscopically or surgically obtained material. The tumor sections were immunohistochemicaly stained with CD117, CD34, NF, S100, αSMA, desmin, caldesmon and mast cell antigen. All leiomyomas showed diffuse positivity for αSMA, caldesmon and desmin. All of them had CD117 and CD34 positive cells morphologically identical to the interstitial cells of Cajal between smooth muscle fibers, 5 had S-100 and NF positive cells and 2 show...
Study design:Cervical spondylotic myelopathy (CSM) represents the most commonly acquired cause of spinal cord dysfunction among individuals over 55 years old. The pathophysiology of the disease involves static and dynamic mechanical... more
Study design:Cervical spondylotic myelopathy (CSM) represents the most commonly acquired cause of spinal cord dysfunction among individuals over 55 years old. The pathophysiology of the disease involves static and dynamic mechanical factors, which are the result of chronic degeneration. The clinical course of the disease remains unpredictable. In the past, many experimental animal models have been developed to study the
Immunohistochemical (IHC) assays performed on formalin-fixed paraffin-embedded (FFPE) tissue sections traditionally have been semi-quantified by pathologist visual scoring of staining. IHC is useful for validating biomarkers discovered... more
Immunohistochemical (IHC) assays performed on formalin-fixed paraffin-embedded (FFPE) tissue sections traditionally have been semi-quantified by pathologist visual scoring of staining. IHC is useful for validating biomarkers discovered through genomics methods as large clinical repositories of FFPE specimens support the construction of tissue microarrays (TMAs) for high throughput studies. Due to the ubiquitous availability of IHC techniques in clinical laboratories, validated IHC biomarkers may be translated readily into clinical use. However, the method of pathologist semi-quantification is costly, inherently subjective, and produces ordinal rather than continuous variable data. Computer-aided analysis of digitized whole slide images may overcome these limitations. Using TMAs representing 215 ovarian serous carcinoma specimens stained for S100A1, we assessed the degree to which data obtained using computer-aided methods correlated with data obtained by pathologist visual scoring. ...
Skin melanoma presents the strongest metastatic capacity and the highest mortality rate of all types of skin cancer, being one of the most aggressive forms of human cancer. Although melanoma represents only 4% of skin cancers, it accounts... more
Skin melanoma presents the strongest metastatic capacity and the highest mortality rate of all types of skin cancer, being one of the most aggressive forms of human cancer. Although melanoma represents only 4% of skin cancers, it accounts for 80% of skin cancer deaths. The aim of this study was the investigation of two specific serum markers for melanoma: S100B and melanoma inhibitory activity in relation to disease development. The longitudinal study was performed on 51 patients diagnosed with skin melanoma and 72 healthy volunteers. For serum S100B and MIA measurement standard ELISA was used. The serum concentration of S100B was found significantly different from normal values only in patients in stage IV, in contrast to MIA, where significant differences occurred as early as stage II. The dynamics of the studied serum markers was in accordance with the skin melanoma evolution, especially for serum MIA. Only both increased S100B and MIA serum levels can indicate the disease evolut...
Glutaryl-CoA dehydrogenase deficiency or glutaric acidemia type I (GA I) is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of predominantly glutaric (GA) and 3-hydroxyglutaric (3OHGA) acids and... more
Glutaryl-CoA dehydrogenase deficiency or glutaric acidemia type I (GA I) is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of predominantly glutaric (GA) and 3-hydroxyglutaric (3OHGA) acids and clinically by severe neurological symptoms and structural brain abnormalities, manifested as progressive cerebral atrophy and acute striatum degeneration following encephalopathic crises, whose pathophysiology is still in debate. Considering that reactive astrogliosis
Biliary Atresia (BA) is rare and genetically complex, and the pathogenesis is elusive. The disease course is variable and can represent heterogeneity, which hinders effective disease management. Deciphering the BA phenotypic variance is a... more
Biliary Atresia (BA) is rare and genetically complex, and the pathogenesis is elusive. The disease course is variable and can represent heterogeneity, which hinders effective disease management. Deciphering the BA phenotypic variance is a priority in clinics and can be achieved by the integrative analysis of genotype and phenotype. We aim to explore the BA phenotypic features and to delineate the source of its variance. The study is a cross-sectional observational study collating with case/control association analysis. One-hundred-and-eighty-one type III non-syndromic BA patients and 431 controls were included for case-control association tests, including 89 patients (47.19% males, born June 15th, 1981 to September 17th, 2007) have detailed clinical records with follow-up of the disease course (median ~17.2 years). BA-association genes from the genome-wide gene-based association test on common genetic variants (CV) and rare copy-number-variants (CNVs) from the genome-wide survey, th...
Fetal death in the mid-trimester of pregnancy is unexplained and no reliable markers are available to identify at-risk women. We aimed to assess use of a fetoprotein and S100B concentrations in amniotic fluid as markers. We did a... more
Fetal death in the mid-trimester of pregnancy is unexplained and no reliable markers are available to identify at-risk women. We aimed to assess use of a fetoprotein and S100B concentrations in amniotic fluid as markers. We did a case-control study in 758 healthy ...
Dermatofibrosarcoma protuberans (DFSP) is an uncommon intermediate-grade soft tissue sarcoma. The tumor is found preferentially on the trunk, whereas the head and neck region are affected in only 10% to 15% of cases. We report the case of... more
Dermatofibrosarcoma protuberans (DFSP) is an uncommon intermediate-grade soft tissue sarcoma. The tumor is found preferentially on the trunk, whereas the head and neck region are affected in only 10% to 15% of cases. We report the case of a 44-year-old woman with a 5-month history of an asymptomatic, firm, yellow nodule in the mucosa of the right cheek measuring 2.5 cm. The clinical diagnosis was lipoma and an excisional biopsy was obtained. Histopathological analysis revealed a proliferation of spindle-shaped mesenchymal cells arranged in interlacing fascicles amidst fibrous stroma. Low mitotic activity (2 mitoses per field) and deep cell infiltration into adipose tissue were observed. These features led to the histopathological diagnosis of a malignant low-grade mesenchymal cell tumor. Immunohistochemical analysis revealed negative staining for α-SMA, S-100, and Bcl-2, but positive staining for Ki-67 (18%) and strong and diffuse staining for CD34. These findings were compatible wi...
Because the pulp tissue extirpated during root canal procedures might serve as a valuable resource with which to assess underlying mechanisms of persistent pain, we sought to determine whether standard Western blotting techniques could be... more
Because the pulp tissue extirpated during root canal procedures might serve as a valuable resource with which to assess underlying mechanisms of persistent pain, we sought to determine whether standard Western blotting techniques could be used to quantify neural proteins in pulp ...
The S100P protein is a member of the S100 family of calcium-binding proteins and possesses both intracellular and extracellular functions. Extracellular S100P binds to the cell surface receptor for advanced glycation end products (RAGE)... more
The S100P protein is a member of the S100 family of calcium-binding proteins and possesses both intracellular and extracellular functions. Extracellular S100P binds to the cell surface receptor for advanced glycation end products (RAGE) and activates its downstream signaling cascade to meditate tumor growth, drug resistance and metastasis. Preventing the formation of this S100P-RAGE complex is an effective strategy to treat various disease conditions. Despite its importance, the detailed structural characterization of the S100P-RAGE complex has not yet been reported. In this study, we report that S100P preferentially binds to the V domain of RAGE. Furthermore, we characterized the interactions between the RAGE V domain and Ca(2+)-bound S100P using various biophysical techniques, including isothermal titration calorimetry (ITC), fluorescence spectroscopy, multidimensional NMR spectroscopy, functional assays and site-directed mutagenesis. The entropy-driven binding between the V domai...
The cardiovascular complications of diabetes represent the leading cause of morbidity and mortality in affected subjects. The impact of hyperglycemia may be both direct and indirect: indirect consequences of elevated blood glucose lead to... more
The cardiovascular complications of diabetes represent the leading cause of morbidity and mortality in affected subjects. The impact of hyperglycemia may be both direct and indirect: indirect consequences of elevated blood glucose lead to generation of advanced glycation endproducts, the products of nonenzymatic glycation/oxidation of proteins/lipids that accumulate in the vessel wall, and are signal transduction ligands for Receptor for AGE (RAGE). Although enhanced in diabetes, AGE accumulation also occurs in euglycemia and aging, albeit to lower degrees, driven by oxidant stress and inflammation. In hyperglycemia, production of 3-deoxyglucosone, at least in part via the polyol pathway, provides an amplification loop to sustain AGE generation, oxidant stress, and vascular activation. Furthermore, recruitment of inflammatory cells bearing S100/calgranulins, also ligands for RAGE, augments vascular dysfunction. We hypothesize that activation of RAGE is a final common pathway that tr...
1. J Dermatol Sci. 2008 Dec;52(3):216-9. Epub 2008 Aug 15. Induction of a microbicidal protein psoriasin (S100A7), and its stimulatory effects on normal human keratinocytes. Niyonsaba F, Hattori F, Maeyama K, Ogawa H, Okamoto K. ...