Squid leucophore-inspired engineering of optically dynamic human cells.

Cephalopods (e.g., squids, octopuses, and cuttlefishes) possess remarkable dynamic camouflage abilities and therefore have emerged as powerful sources of inspiration for the engineering of dynamic optical technologies.

Diagnostic Capabilities of Islet Autoantibodies in Children with New-Onset Type 1 Diabetes Mellitus and Healthy Siblings.

Unlabelled: is to determine the diagnostic utility of several islet autoantibodies and their combinations in order to identify individuals susceptible to type 1 diabetes mellitus (T1DM) among healthy siblings in the pediatric population within the scope of the development of a screening program.

Materials And Methods: A total of 424 children were evaluated, 260 children with new-onset T1DM and 164 healthy children with brothers and/or sisters with T1DM.Blood tests for a complex of autoantibodies to insulin (IAA), tyrosine phosphatase (IA-2A), zinc transporter 8 (ZnT8A), pancreatic β-cells (ICA), and glutamate decarboxylase (GADA) were conducted in all the subjects with the enzyme immunoassay method.

Phase III, placebo-controlled, randomized, double-blind trial of tableted, therapeutic TB vaccine (V7) containing heat-killed administered daily for one month.

Objective: Immunotherapy of tuberculosis (TB) to shorten treatment duration represents an unmet medical need. Orally delivered, tableted TB vaccine (V7) containing heat-killed (NCTC 11659) has been demonstrated in prior clinical studies to be safe and fast-acting immune adjunct.

Methods: The outcome of Phase III trial of V7 containing 10 µg of hydrolyzed was evaluated in 152 patients randomized at 2:1 ratio: V7 ( = 100), placebo ( = 52).

Double-blind, placebo-controlled, 1:1 randomized Phase III clinical trial of Immunoxel honey lozenges as an adjunct immunotherapy in 269 patients with pulmonary tuberculosis.

Aim: Safer and shorter antituberculosis treatment (ATT) regimens represent the unmet medical need.

Patients & Methods: The patients were randomly assigned into two arms: the first (n = 137) received once-daily sublingual honey lozenge formulated with botanical immunomodulator Immunoxel and the second (n = 132) received placebo lozenges along with conventional ATT. Immunoxel and placebo arms were demographically similar: 102 versus 106 had drug-susceptible TB; 28 versus 20 multidrug-resistant TB (MDR-TB); 7 versus 7 extensively drug-resistant TB (XDR-TB); and 22 versus 20 TB-HIV.

Association of interleukins genes polymorphisms with multi-drug resistant tuberculosis in Ukrainian population.

Introduction: Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined.

ATP-gated P2X3 receptors constitute a positive autocrine signal for insulin release in the human pancreatic beta cell.

Extracellular ATP has been proposed as a paracrine signal in rodent islets, but it is unclear what role ATP plays in human islets. We now show the presence of an ATP signaling pathway that enhances the human beta cell's sensitivity and responsiveness to glucose fluctuations. By using in situ hybridization, RT-PCR, immunohistochemistry, and Western blotting as well as recordings of cytoplasmic-free Ca(2+) concentration, [Ca(2+)](i), and hormone release in vitro, we show that human beta cells express ionotropic ATP receptors of the P2X(3) type and that activation of these receptors by ATP coreleased with insulin amplifies glucose-induced insulin secretion.

Corticosteroids and montelukast: effects on airway epithelial and human umbilical vein endothelial cells.

Our primary objective was to investigate the possible contribution of controller medications to asthmatic airway remodeling, by (1) comparing the apoptotic and necrotic effects of several corticosteroids and montelukast on cultured airway human bronchial surface epithelial (16HBE) and submucosal (Calu3) cells; (2) measuring epithelial shedding potential and desmosome length in response to a cytokine challenge, with or without co-administered corticosteroids; and (3) studying corticosteroids and montelukast effects on inter-cellular adhesion molecule (ICAM) expression in both 16HBE and human umbilical vein endothelial cells (HUVEC). For this purpose, apoptosis, necrosis, and ICAM expression were quantified by flow cytometry, with 16HBE cells sensitive to both the apoptotic and necrotic effects of dexamethasone and montelukast; Calu3 cells sensitive only to budesonide. Transmission electron microscopy revealed decreased desmosome length in the presence of cytokines (TNF-alpha and INF-gamma), with corticosteroids counteracting this reduction.

Possible role of an ischemic preconditioning-like response mechanism in K(ATP) channel opener-mediated protection against streptozotocin-induced suppression of rat pancreatic islet function.

Potassium channel openers (KCOs) decrease insulin secretion from beta-cells. Some KCOs also protect against damage to beta-cell function and type 1 diabetes in animal models. Previously we have found that the KCO NNC 55-0118 counteracted islet cell dysfunction, and this was associated with a lowering of the mitochondrial membrane potential (Deltapsi).

Transforming growth factor-beta-activated protein kinase 1-binding protein (TAB)-1alpha, but not TAB1beta, mediates cytokine-induced p38 mitogen-activated protein kinase phosphorylation and cell death in insulin-producing cells.

Previous studies have indicated that the p38 MAPK participates in signaling events that lead to the death of the insulin-producing beta-cell. The aim of the present study was to elucidate the role of the TGF-beta-activated protein kinase 1-binding protein 1 (TAB1) in the cytokine-induced activation of p38. Levels of TAB1 mRNA and protein were analyzed by real-time PCR and immunoblotting, and TAB1 expression in mouse and human islet cells was down-regulated using lipofection of diced-small interfering RNA.

Role of TAB1 in nitric oxide-induced p38 activation in insulin-producing cells.

The aim of present study was to elucidate the role of TAB1 in nitric oxide-induced activation of p38 MAPK. For this purpose we over-expressed TAB1 in insulin-producing beta-TC6 cells. We observed in cells transiently over-expressing TAB1 that p38 activation was enhanced in response to DETA/NONOate.

Imatinib mesylate (Gleevec) protects against streptozotocin-induced diabetes and islet cell death in vitro.

The tyrosine kinase inhibitor imatinib mesylate (Gleevec) has been demonstrated to protect various cell types from death by inhibition of Abelson tyrosine kinase (c-Abl). The aim of the present study was to establish whether imatinib protects the insulin producing beta-cell from the different apoptosis promoting agents in vitro and whether imatinib counteracts streptozotocin-induced diabetes in NMRI mice. We observe that imatinib attenuated the actions of several different death promoting substances.

Role of MKK3 and p38 MAPK in cytokine-induced death of insulin-producing cells.

The aim of the present investigation was to elucidate further the importance of p38 MAPK (mitogen-activated protein kinase) in nitric oxide- and cytokine-induced beta-cell death. For this purpose, isolated human islets were treated with d-siRNA (diced small interfering RNA) and then exposed to the nitric oxide donor DETA/NONOate [2,2'-(hydroxynitrosohydrazono)bis-ethanamine]. We observed that cells treated with p38alpha-specific d-siRNA, but not with d-siRNA targeting GL3 (a firefly luciferase siRNA plasmid) or PKCdelta (protein kinase Cdelta), were protected against nitric oxide-induced death.

Effect of cytokines on ICAM-1 and ZO-1 expression on human airway epithelial cells.

The presence of adhesion molecules on airway epithelial cells may be important in recruiting leukocytes to the epithelium. The study aimed at investigating the effects of interleukin (IL)-4, IL-8, IL-13 and interferon-gamma (IFN-gamma) on cell viability and intracellular adhesion molecule (ICAM)-1 and zonula occludens protein (ZO)-1 expression on cultured human basal and columnar airway epithelial cells. Cycloheximide (CHX) induced cell death in both cell lines.

Distinct organization of the candidate tumor suppressor gene RFP2 in human and mouse: multiple mRNA isoforms in both species- and human-specific antisense transcript RFP2OS.

In the present study, we describe the human and mouse RFP2 gene structure, multiple RFP2 mRNA isoforms in the two species that have different 5' UTRs and a human-specific antisense transcript RFP2OS. Since the human RFP2 5' UTR is not conserved in mouse, these findings might indicate a different regulation of RFP2 in the two species. The predicted human and mouse RFP2 proteins are shown to contain a tripartite RING finger-B-box-coiled-coil domain (RBCC), also known as a TRIM domain, and therefore belong to a subgroup of RING finger proteins that are often involved in developmental and tumorigenic processes.

[Fundamental and applied aspects of comparative genomics of vertebrates].

The Human Genome Project stimulated the development of efficient strategies and relevant hardware for complete genome sequencing. The comparative genomic approach extends the possibilities of using the sequencing data to identify new genes or conserved regulatory regions by means of nucleotide sequence alignment of the particular regions of the mouse and human genomes, or to trace the evolutionary events resulting in the genome structure of modern mammals. The review focuses on the use of new molecular cytogenetic methods along with computer-aided analysis of the genomes in vertebrates.

Overexpression of the Shb SH2 domain-protein in insulin-producing cells leads to altered signaling through the IRS-1 and IRS-2 proteins.

Background: Overexpression of the Src homology 2 domain protein Shb in beta-cells of transgenic mice has been shown to promote an increased beta-cell mass. To investigate the mechanisms by which Shb controls the beta-cell mass, we have presently studied the effects of Shb overexpression on the IRS-1-induced signaling pathway in mouse islet beta-cells and in insulin-producing RINm5F cells and correlated these effects to growth and death patterns.

Materials And Methods: Shb overexpression was achieved in RINm5F cells by selection of stable clones or by FACS purification of transiently transfected cells.

[Transcription map of the 13q14 region, frequently deleted in B-cell chronic lymphocytic leukemia patients].

Deletions in the region located between the STS markers D13S1168 and D13S25 on chromosome 13 are the most frequent genomic changes in patients with B-cell chronic lymphocytic leukemia (B-CLL). After sequencing of this region, two novel candidate genes were identified: C13orf1 (chromosome 13 open reading frame 1) and PLCC (putative large CLL candidate). Analysis of the repeat distribution revealed two subregions differing in composition of repetitious DNA and gene organization.

Comparative sequence analysis of a region on human chromosome 13q14, frequently deleted in B-cell chronic lymphocytic leukemia, and its homologous region on mouse chromosome 14.

Previous studies have indicated the presence of a putative tumor suppressor gene on human chromosome 13q14, commonly deleted in patients with B-cell chronic lymphocytic leukemia (B-CLL). We have recently identified a minimally deleted region encompassing parts of two adjacent genes, termed LEU1 and LEU2 (leukemia-associated genes 1 and 2), and several additional transcripts. In addition, 50 kb centromeric to this region we have identified another gene, LEU5/RFP2.

[The use of xenon irradiator in otology].

Xenon irradiator " " (Yakhont-F) has been used in combined treatment of chronic purulent diseases of the external and middle ear in 50 patients. The unit is supplied with flexible multifiber light guides which can operate in the sites not easily accessible for other instruments. Such radiation leads to good bactericidal, antiinflammatory and antiedema effects.

[Effect of captopril and reserpine on the activity of certain neuropeptide metabolism enzymes].

Chronic consumption of the highly specific angiotension-converting enzyme inhibitor captopril was found to decrease the activity of the enzyme in the rat hypothalamus and striatum and to enhance it in the pituitary and blood serum. The agent also increased the activity of carboxypeptidase N in the serum and that of carboxypeptidase H in the pituitary. Reserpine, a catecholaminergic blocking agent, reduces the pituitary and serum activities of angiotensin-converting enzyme and activates soluble carboxypeptidase H in the pituitary and striatum and membrane-bound carboxypeptidase in the hypothalamus and striatum.

[Diagnostic informative value of enzyme tests in the detection of pancreatic involvement in systemic scleroderma].

Thirty-three patients with systemic scleroderma were examined using a complex of enzymatic tests to detect pancreatic involvement. The diagnostic informative value of these tests was found to be not inferior to that of acknowledged instrumental methods of examination: pancreatic involvement was detected in 25 of the 33 patients with systemic scleroderma.

[Use of helium-neon laser device LTM-01 in the treatment of patients with chronic suppurative otitis media].

The all-purpose small-sized portable helium-neon laser unit LTM-I has been tested in a clinic. The unit is constructed on the basis of a quantum generator of 0.5-1.