Pharmacogenomics of coronary artery response to intravenous gamma globulin in kawasaki disease.

Kawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that can result in acute vasculitis. The mechanism of coronary artery aneurysms (CAA) in KD despite intravenous gamma globulin (IVIG) treatment is not known. We performed a Whole Genome Sequencing (WGS) association analysis in a racially diverse cohort of KD patients treated with IVIG, both using AHA guidelines.

Epigenetic age in African American adolescents with type 2 diabetes: A cross-sectional case-control study protocol.

Background And Aims: Type 2 diabetes (T2D) is a disease caused by a relative insulin deficiency compared to the significant insulin requirement needed by the body to achieve glycemic control. T2D in adolescence appears to be increasing in prevalence over the past several decades, necessitating studies to understand for the onset of the disease to occur early in the lifespan. Given the high burden of disease, specifically in young African American adolescents, our study chose to focus initially on feasibility of recruitment of this population.

RNA-seq analysis identifies transcriptomic profiles associated with anal cancer recurrence among people living with HIV.

Background: Chemoradiation therapy (CRT) is the standard of care for squamous cell carcinoma of the anus (SCCA), the most common type of anal cancer. However, approximately one fourth of patients still relapse after CRT.

Methods: We used RNA-sequencing technology to characterize coding and non-coding transcripts in tumor tissues from CRT-treated SCCA patients and compare them between 9 non-recurrent and 3 recurrent cases.

Discrimination between G/C Binding Sites by Olivomycin A Is Determined by Kinetics of the Drug-DNA Interaction.

Olivomycin A (OA) exerts its cytotoxic potency due to binding to the minor groove of the G/C-rich DNA and interfering with replication and transcription. Screening of the complete set of tetranucleotide G/C sites by electrophoretic mobility gel shift assay (EMSA) revealed that the sites containing central GC or GG dinucleotides were able to bind OA, whereas the sites with the central CG dinucleotide were not. However, studies of equilibrium OA binding in solution by fluorescence, circular dichroism and isothermal titration calorimetry failed to confirm the sequence preference of OA, indicating instead a similar type of complex and comparable affinity of OA to all G/C binding sites.

Establishment and characterization of immortalized mouse ameloblast-like cell lines.

Objectives: Enamel organ epithelium (EOE) gives rise to the major epithelial-derived cell types of tooth including the ameloblasts. The formation of enamel, termed amelogenesis, occurs through the cytodifferentiation of ameloblasts, ultimately leading to apoptosis and necrosis of these cells with eruption. Therefore, studies regarding enamel matrix formation and bioengineering have been limited.

Gene-Expression Analysis Identifies IGFBP2 Dysregulation in Dental Pulp Cells From Human Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder affecting osteoblast differentiation, chondrocyte maturation, skeletal morphogenesis, and tooth formation. Dental phenotype in CCD include over-retained primary teeth, failed eruption of permanent teeth, and supernumerary teeth. The underlying mechanism is unclear.

Divalent cations are dispensable for binding to DNA of a novel positively charged olivomycin A derivative.

The current model of binding of the antitumor antibiotic olivomycin A (1) to GC-rich DNA regions presumes that coordination of the magnesium divalent cation with drug dimers is necessary for binding of 1 into the minor groove of the DNA duplex. Previously we have synthesized the derivatives of 1 termed 'short acid' (2) and its N,N-dimethylaminoethylamide (3). The latter compound demonstrated an improved tolerance in vivo compared to 1 and good therapeutic potency in animal models.

Light-induced oxidation of the telomeric G4 DNA in complex with Zn(II) tetracarboxymethyl porphyrin.

Structure-specific ligands are convenient tools for the recognition, targeting or probing of non-canonical DNA structures. Porphyrin derivatives exhibit a preference for interaction with G-quadruplex (G4) structures over canonical duplex DNA and are able to cause photoinducible damage to nucleic acids. Here, we show that Zn(II) 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium)porphyrin ( ZNP1: ) interacts with different conformations of the telomeric sequence d(TAGGG(TTAGGG)) at submicromolar concentrations without any detectible disturbance of the particular fold.

Effects of FGFR Signaling on Cell Proliferation and Differentiation of Apert Dental Cells.

The Apert syndrome is a rare congenital disorder most often arising from S252W or P253R mutations in fibroblast growth factor receptor (FGFR2). Numerous studies have focused on the regulatory role of Apert FGFR2 signaling in bone formation, whereas its functional role in tooth development is largely unknown. To investigate the role of FGFR signaling in cell proliferation and odontogenic differentiation of human dental cells in vitro, we isolated dental pulp and enamel organ epithelia (EOE) tissues from an Apert patient carrying the S252W FGFR2 mutation.

Reduced Dentin Matrix Protein Expression in Camurati-Engelmann Disease Transgenic Mouse Model.

Unlabelled: Overexpression of transforming growth factor-β1 (TGF-β1) has been shown to lead to mineralization defects in both the enamel and dentin layers of teeth. A TGFB1 point mutation (H222D), derived from published cases of Camurati-Engelmann disease (CED), has been shown to constitutively activate TGF-β1, leading to excess bone matrix production. Although CED has been well documented in clinical case reports, there are no published studies on the effect of CED on the dentition.

[Stimulation of DNA molecules association with amphiphilic derivatives of 1,3-diazaadamantane containing hydrophobic side chanins].

Earlier, a new class of compounds--amphiphilic derivatives of 1,3-diazaadamantanes, capable of facilitating the strand exchange in the system of short oligonucleotides was revealed. Longer hydrophobic side chains of 1,3-diazaadamantanes promoted stronger acceleration of the reaction. In this study, interaction with DNA of two 1,3-diazaadamantane derivatives containing different side chains was investigated by use of optical methods.

Preferential DNA photocleavage potency of Zn(II) over Ni(II) derivatives of carboxymethyl tetracationic porphyrin: the role of the mode of binding to DNA.

The porphyrin-based photosensitizers capable of binding to DNA are perspective drug candidates. Here we report the interactions with calf thymus DNA of 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium)porphyrin (P1) and its derivatives containing Zn(II) or Ni(II) in the coordination sphere. These interactions were studied with absorption and circular dichroism spectroscopy.

Establishment of Singleton-Merten syndrome pulp cells: evidence of mineralization dysregulation.

Singleton-Merten syndrome (SMS) is a rare disease with a phenotype of dental dysplasia. Currently, the underlying mechanism of this disease is unknown. In order to investigate the functional mechanism of the SMS tooth phenotypes, we isolated dental pulp tissue and established SMS primary pulp cells.

Novel multi-targeting anthra[2,3-b]thiophene-5,10-diones with guanidine-containing side chains: interaction with telomeric G-quadruplex, inhibition of telomerase and topoisomerase I and cytotoxic properties.

Novel generations of antitumor anthraquinones are expected to be advantageous over the conventional chemotherapeutic agents. Previous structure-activity relationship studies demonstrated an importance of the positively charged side chains conjugated to anthra[2,3-b]thiophene-5,10-dione scaffolds. Exploring a role of individual side chain moieties in binding to the duplex and G-quadruplex DNA, modulation of telomerase and topoisomerase I activities, intracellular accumulation and cytostatic potency, we herein analyzed a series of reported and newly synthesized guanidine-containing derivatives of anthra[2,3-b]thiophene-5,10-dione.

[Complexes of antiparallel telomeric G-quadruplex d(TTAGGG)4 with carboxymethyl tetracationic porphyrins].

Porphyrins comprise a chemical class widely used in drug design. Cationic porphyrins may bind to DNA guanine quadruplexes. We report the parameters of binding of 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium)porphyrin (P1) and 5,10,15,20-tetrakis(N-etoxy-carbonylmethyl-4-pyridinium)porphyrin (P2) to antiparallel telomeric G-quadruplex formed by d(TTAGGG)4 sequence (TelQ).

Adenovirus gene transfer to amelogenesis imperfecta ameloblast-like cells.

To explore gene therapy strategies for amelogenesis imperfecta (AI), a human ameloblast-like cell population was established from third molars of an AI-affected patient. These cells were characterized by expression of cytokeratin 14, major enamel proteins and alkaline phosphatase staining. Suboptimal transduction of the ameloblast-like cells by an adenovirus type 5 (Ad5) vector was consistent with lower levels of the coxsackie-and-adenovirus receptor (CAR) on those cells relative to CAR-positive A549 cells.

Differential enamel and osteogenic gene expression profiles in odontogenic tumors.

Odontogenic tumors occur within the jaw bones and may be derived from odontogenic epithelium or ectomesenchyme or contain active components of both tissue types. We investigated the gene expression profile of enamel matrix proteins (EMPs), genes related to osteogenesis, and the mineralization process in odontogenic tumor cell populations focusing on an ameloblastoma (AB-1), a keratocystic odontogenic tumor (KCOT-1), and a calcifying epithelial odontogenic tumor (CEOT-1). All cell populations were shown to be epithelial in origin by CK14 expression.

α-Galactosidase A expressed in the salivary glands partially corrects organ biochemical deficits in the fabry mouse through endocrine trafficking.

Fabry disease is caused by an X-linked deficiency of the lysosomal enzyme α-galactosidase A (GLA) and has been treated successfully with enzyme replacement therapy (ERT). Gene therapy has been proposed as an alternative to ERT due to the presumed advantages of continuous, endogenous production of the therapeutic enzyme. GLA production in the liver and its therapeutic efficacy in the Fabry mouse have been demonstrated previously with various viral vector systems.

Calcium/calmodulin-dependent kinase II regulates notch-1 signaling in prostate cancer cells.

Notch signaling is associated with prostate osteoblastic bone metastases and calcium/calmodulin-dependent kinase II (CaMKII) is associated with osteoblastogenesis of human mesenchymal stem cells. Here we show that prostate cancer cell lines C4-2B and PC3, both derived from bone metastases and express Notch-1, have all four isoforms of CaMKII (alpha, beta, gamma, delta). In contrast, prostate cancer cell lines LNcaP and DU145, which are not derived from bone metastases and lack the Notch-1 receptor, both lack the alpha isoform of CaMKII.

Colorectal cancer and hypercholesterolemia: review of current research.

Aim: In spite of ample research about a high level of cholesterol in the blood of patients with colorectal cancer (CRC), the relationship between factors causing hypercholesterolemia and factors leading to CRC development is not fully investigated. The purpose of this article is to provide a review of the current research about the risk factors leading to the development of hypercholesterolemia and CRC, and to show the relationship between these factors, hypercholesterolemia and CRC with the implication for CRC preventive and treatment practices.

Methods: A systematic search of MEDLINE and PUBMED databases between 1990 and 2005 was conducted to locate the studies that investigated the risk factors causing CRC and hypercholesterolemia.