Proteinuria in early detection of human leptospirosis

Background: Leptospirosis is an infectious disease caused by spirochetes bacteria Leptospira spp. and is reported from all over the world. As the clinical signs and symptoms of Leptospirosis often are nonspecific and the disease is early mistaken for other major infectious febrile illness, laboratory test to confirm the clinical diagnosis thus is essential for optimal treatment and patient management.Methods: Serum and urine samples were collected from patients clinically suspected cases of Leptospirosis. Preparations of urine concentrate by precipitation and centrifugation.Results: It was interesting to note that immunoglobulins are present in the urine protein concentrate of patients with Leptospirosis on the day of admission in the hospital, with urine albumin reports either positive or negative. By ELISA test it was noted that antibodies present in urine and serum were of both IgM and IgG class against the Leptospiral antigens from three pathogenic serovars and one non-pathogenicserovars. In the immunospot test which was done and compared with standard ELISA test for serum antibodies using same antigen showed that antibodies present in urine protein concentrate, which was collected on the day of admission when patients come with suspecting symptoms of Leptospirosis.Conclusions: Proteinuria is the most frequent abnormality noted in all patients at some stage of illness. This is the first report on the presence of immunoglobulins in urine samples, which were found to be of IgM and IgG classes. These findings are of significant diagnostic potential as a simple immune-spot test can be done for detecting anti-leptospiral antibodies in urine samples of suspected cases. The present attempt was aimed at developing an immunospot test, a simple and rapid diagnostic test to detect Leptospirosis using urine samples of clinically suspected patients of the infection at the earliest. It was found to be in good correlation with standard ELISA method which is being used to detect serum antibodies in Leptospira infected patients using the same antigen

DMP1 Activates Osteolytic Cycle in a Tumor Environment

Bone metastasis is one of the skeletal malignancies that could be caused by breast cancer. Dentin matrix protein 1 (DMP1) is an acidic noncollagenous protein localized specifically in the mineralized matrix of bone and dentin. It is a multifunctional protein, involved in gene regulation (within the cell) and HAP nucleation (in the ECM). DMP1 is endocytosed by preosteoblasts, triggering the calcium dependent and calcium independent signaling pathways resulting in a series of downstream events leading to osteoblast differentiation. These signaling events facilitate the activation of a calcium dependent stress-induced p38 MAP kinase and a calcium independent integrin mediated ERK1/2 MAP kinase pathway resulting in the expression of downstream target genes such as Runx2 and osteocalcin. Results from this study have shown that the osteoblast cells upon differentiation secrete receptor activator of nuclear factor kappa B ligand (RANKL) that stimulates the differentiation of precursor monocytes to osteoclasts. The study also focuses on identifying the role of DMP1 in breast cancer cells that could enhance osteoclast formation thereby accelerating bone resportion. Thus, the study reveals a new mechanism by which DMP1 can activate the vicious cycle leading to the aggressive growth and behavior of the cancer cells. To address the mechanism by which DMP1 might contribute to the osteolytic process, DMP1 was overexpressed in the metastatic cancer cell line MDA MB231. Upregulation of markers like Runx2, MMP2, MMP9, RANKL, OPN, BSP, VEGF and the activation of Smad2/3 and MAP kinase pathways (p38 and ERK1/2 pathways) were observed in overexpressed cells. Results from this study have shown that DMP1 secreted by the breast cancer cells into the extracellular environment could stimulate the differentiation of osteoblasts, leading to the secretion of factors that signal monocytes to differentiate to osteoclast thus resulting in bone metastasis. Overall, the results obtained from this study identify a new role for DMP1 in the differentiation of breast cancer tumor cells that may be directly related to their metastatic potential

Salivary Glands and Its Myriad Forms of Cancers , Diagnosis And Therapy

Salivary gland is a complex, compoundsecretory tissue seen in the oral cavity, which produces saliva and maintains oral homeostasis.Salivary gland diseases can range from swelling of the gland to Malignancies. In order to understand the localization and the diagnosis of the salivary gland diseases, it is important to understand the development, structure and function of the gland. This review article summaries the biology, diseases and the diagnostic tool available to investigate and evaluate the disease.nbs

Exososome: Potential Biomarker for Cancer

Transformation is a common phenomenon that occurs in a cancer environment. As a result of tumorogenesis, normal cells are transformed into cancer cells. Researchers have shown that multicellular vesicles known as exosomes secreted by Malignant cells have the potential to induce this normal cell transformation. Accumulating evidence indicates that exosomes play important roles in cancer. Exosomes are known to play decisive roles in tumorogenesis, growth, progression, metastasis, and drug resistance by transferring oncogenic proteins and nucleic acids that modulates the activity of recipient cells. In this review, we will unveil the role of exosomes as communication molecules in cancer. Exosome shuttle proteins and nucleic acids and so have been suggested as novel diagnostic and prognostic indicators for a variety of cancers. Currently, tumor-derived exosomes are utilized as vaccines and as carriers for drugs and small molecules in pre-clinical studies and clinical trials

DPP Activates Integrin-Mediated Anchorage-Dependent Signals in undifferentiated mesenchymal cells

DPP, a major noncollagenous protein of the dentin matrix is a highly acidic protein and binds Ca2+ avidly and thus linked to matrix mineralization. Here, we demonstrate that the RGD domain in DPP can bind to integrins on the cell surface of undifferentiated mesenchymal stem cells and pulp cells. This coupling generates intracellular signals that are channeled along cytoskeletal filaments and activates the nonreceptor tyrosine kinase FAK, which plays a key role in signaling at sites of cellular adhesion. The putative FAK autophosphorylation site Tyr397 is phosphorylated during focal adhesion assembly induced by DPP on the substrate. We further demonstrate that these intracellular signals propagate through the cytoplasm and activate anchorage-dependent ERK signaling. Activated ERK, translocates to the nucleus and phosphorylates the transcription factor ELK-1which in turn coordinate the expression of downstream target genes such as DMP1 and DSP. These studies suggest a novel paradigm which demonstrates that extracellular DPP can induce intracellular signaling which can be propagated to the nucleus and thus alter gene activities

Activation of the ERK1/2 Mitogen-Activated Protein Kinase Cascade by Dentin Matrix Protein 1 Promotes Osteoblast Differentiation

DMP1 has been shown to play many roles in osteogenesis. We recently demonstrated that calcium-mediated stress kinase activation by DMP1 leads to osteoblast differentiation. In this study we demonstrate that DMP1 can also activate the extracellular signal-regulated kinase (ERK)-MAPK pathway. This activation was mediated through the RGD integrin-binding domain in DMP1. Further, we demonstrate that Runx2, an essential transcription factor, is stimulated by the ERK-MAPK pathway. Copyright © 2011 S. Karger AG, Base

Activation of the ERK1/2 Mitogen-Activated Protein Kinase Cascade by Dentin Matrix Protein 1 Promotes Osteoblast Differentiation

DMP1 has been shown to play many roles in osteogenesis. We recently demonstrated that calcium-mediated stress kinase activation by DMP1 leads to osteoblast differentiation. In this study we demonstrate that DMP1 can also activate the extracellular signal-regulated kinase (ERK)-MAPK pathway. This activation was mediated through the RGD integrin-binding domain in DMP1. Further, we demonstrate that Runx2, an essential transcription factor, is stimulated by the ERK-MAPK pathway