pan-filoviral cytotoxic t-cell: Topics by WorldWideScience.org

Decreased semen quality in a male infected with malaria.

Autoreactive cytotoxic CD8 T-cells (CTLs) play a key pathogenic role in the destruction of insulin-producing beta-cells resulting in type 1 diabetes. However, knowledge regarding their targets is limited, restricting the ability to monitor the course of the disease and immune interventions. In a multi-step discovery process to identify novel CTL epitopes in human preproinsulin (PPI), PPI was digested with purified human proteasomes, and resulting COOH-fragments aligned with algorithm-predicted HLA-binding peptides to yield nine potential HLA-A1, -A2, -A3 or -B7-restricted candidates. An UV-exchange method allowed the generation of a repertoire of multimers including low-affinity HLA-binding peptides. These were labeled with quantum dot-fluorochromes and encoded in a combinatorial fashion, allowing parallel and sensitive detection of specific, low-avidity T-cells. Significantly increased frequencies of ...

2011-05-31

Ophthalmic abnormalities in patients with cutaneous T-cell lymphoma.

A 33-year-old male of proven fertility suffered six attacks of malaria while resident in an African country. For this he received anti-malarial drugs. Semen analysis performed after the fourth attack, and repeated during the following 2 years after his return to Israel, revealed severe oligozoospermia, necrozoospermia and occasionally even azoospermia. Immunological examination of the patient revealed an inverse ratio of T-cell subsets and mast cell degranulation in response to palludrin. Twenty-five months after the last attack of malaria a significant improvement was found in semen quality and there was an increase in the ratio of T-helper to T-suppressor cytotoxic cells. These observations indicate that although malaria and its treatment may affect spermatogenesis, recovery may be expected eventually. PMID:3500921

1987-10-01

Cytotoxic Sesquiterpenoid from the Seeds of Amomum xanthioides

PURPOSE: To determine the frequency of ophthalmic abnormalities in patients with cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome) and T-cell lymphoma involving the skin and...Full Text Available

1998-01-01

KoreaScience (Korea)

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2011-03-01

Interaction of an immunodominant epitope with Ia molecules in T-cell activation

DEFF Research Database (Denmark)

Udgivelsesdato: 1988-Jul

1988-01-01

Inhibitor of DNA synthesis is present in normal chicken serum

Genetic heterogeneity in human T-cell leukemia/lymphoma virus type II.

The authors have found that heat-inactivated serum (57/sup 0/C for 1 hour) from normal chickens reduces the proliferation of mitogen-stimulated chicken and murine splenocytes as well as some transformed mammalian lymphoblastoid cell lines. Greater than a 50% reduction in /sup 3/H-thymidine incorporation was observed when concanavalin A (Con A)-activated chicken splenocytes that were cultured in the presence of 10% autologous or heterologous serum were compared to mitogen-stimulated cells cultured in the absence of serum. Normal chicken serum (10%) also caused greater than 95% suppression of /sup 3/H-thymidine incorporation by bovine (EBL-1 and BL-3) and gibbon ape (MLA 144) transformed lymphoblastoid cell lines. The only cell line tested that was not inhibited by chicken serum was an IL-2-dependent, murine cell line. Chicken serum also inhibited both /sup 3/H-thymidine incorporation and IL-2 synthesis by Con A-activated murine splenocytes. Suppression was caused by actions other than ...

1986-03-05

Epidermal keratinocytes do not activate peripheral T-cells: interleukin-10 as a possible regulator

DNA from the peripheral blood mononuclear cells of 17 different individuals infected with human T-cell lymphoma/leukemia virus type II (HTLV-II) was successfully amplified by the polymerase chain reaction...Full Text Available

1993-03-01

The mitogenic activity of human T-cell leukemia virus type I is T-cell associated and requires the CD2/LFA-3 activation pathway.

The immunogenicity of allogeneic cultured human epidermal keratinocytes (cHEKs) has been studied in several models with contradictory results. We studied human T-cell activation in an in vitro...Full Text Available

2008-11-01

Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers.

The presence of a high number of activated T cells in the bloodstream and spontaneous proliferation of peripheral blood mononuclear cells in vitro are striking characteristics of human T-cell leukemia...Full Text Available

1993-06-01

Chimeric Matrix Proteins Encoded by Defective Proviruses with Large Internal Deletions in Human T-Cell Leukemia Virus Type 1-Infected Humans

Although human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), the role of viral gene expression in the progression to and maintenance of the...Full Text Available

1992-04-01

Intracellular Calcium Concentration in the Glutamate-induced Cytotoxicity in PCl2 Cell

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other diseases....Full Text Available

2000-05-01

KoreaScience (Korea)

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2002-12-01

Imaging immune response in vivo

Mutagenic and cytotoxic activity of doxorubicin and daunorubicin derivatives on prokaryotic and eukaryotic cells.

PurposeClinical trials have commenced to evaluate the feasibility of targeting malignant gliomas with genetically engineered cytolytic T-cells (CTLs) delivered directly...Full Text Available

2008-06-15

Special regulatory T-cell review: A rose by any other name: from suppressor T cells to Tregs, approbation to unbridled enthusiasm

The mutagenic and cytotoxic activity of two newly synthesized doxorubicin derivatives and of one daunorubicin derivative were studied in V79 Chinese hamster cells and bacteria (Salmonella typhimurium...Full Text Available

1984-07-01

Reduced expression of a human V beta 6.1 T-cell receptor allele.

In the early 1970s a spate of papers by research groups around the world provided evidence for a negative regulatory role of thymus-derived lymphocytes (T cells). In 1971, Gershon and Kondo published...Full Text Available

2008-01-01

Evaluation of T-cell receptor gene rearrangements in patients with recurrent patch/plaque (T2) CTCL (mycosis fungoides).

We have previously described an allelic polymorphism in the V beta 6.1 T-cell receptor gene. The V beta 6.1B allele is associated with disease in a subgroup of patients with juvenile rheumatoid arthritis....Full Text Available

1993-05-15

Clinical and laboratory experience of vorinostat (suberoylanilide hydroxamic acid) in the treatment of cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma is typically a clonal neoplasm of epidermotropic CD4+ T-lymphocytes that includes the entity mycosis fungoides (MF). After identification of patients with recurrent MF treated...Full Text Available

1999-11-01

Autocrine regulation of T-cell activation by ATP release and P2X₇ receptors

The most common cutaneous T-cell lymphomas (CTCLs) – mycosis fungoides (MF) and Sézary Syndrome – are characterised by the presence of clonally expanded, skin-homing helper-memory...Full Text Available

2006-12-01

Setting the standard in T-cell-depleted haploidentical transplantation and beyond

T-cell activation requires the influx of extracellular calcium, although mechanistic details regarding such activation are not fully defined. Here, we show that P2X₇ receptors play a key...Full Text Available

2009-06-01

British Library Electronic Table of Contents (United Kingdom)

Much progress has been made in the clinical, biological and technical aspects of the T-cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT). Our experience demonstrates that infusing a megadose of extensively T-cell-depleted hematopoietic peripheral blood stem cells after an immuno-myeloablative conditioning regimen in acute leukemia patients ensures sustained engraftment with minimal GvHD without the need of any post-transplant immunosuppressive treatment. Since our first successful pilot study, our efforts have concentrated on developing new conditioning regimens, optimizing the graft processing and improving the post-transplant immunological recovery. The results we have so far achieved in high risk acute leukemia patients show that haploidentical transplantation ...

2011-01-01

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Hepatosplenic T-cell lymphoma is a distinct rare entity: Diagnosis by fine-needle aspiration cytology

British Library Electronic Table of Contents (United Kingdom)

Abstract In this brief report, we have described the fine-needle aspiration cytology (FNAC) of a hepatosplenic T-cell lymphoma (HSTCL) in a 60-year-old female patient. The patient complained of fever and heaviness of left upper abdomen. Ultrasound-guided FNAC of the spleen showed immature lymphoid cells, and a diagnosis of primary non-Hodgkin lymphoma of spleen was offered. Subsequently, the patient underwent splenectomy and wedge biopsy of liver that confirmed the cytological diagnosis. The lymphoma cells were positive for CD3 immunostain. Primary hepatosplenic T-cell lymphoma is a rare entity and may often pose diagnostic problems on FNAC. Diagn. Cytopathol. 2010. 2010 Wiley-Liss, Inc.

2011-01-01

Transcriptomic analysis supports similar functional roles for the two thymuses of the tammar wallaby

The influence of MHC polymorphism on the selection of T-cell determinants of FMDV in cattle.

BackgroundThe thymus plays a critical role in the development and maturation of T-cells. Humans have a single thoracic thymus and presence of a second thymus is considered an anomaly....Full Text Available

The Structure of the Dust Mite Allergen Der p 7 Reveals Similarities to Innate Immune Proteins

There is a quest for the development of a new generation of vaccines consisting of well-defined subunit antigens. For a number of practical reasons it is attractive to develop vaccines on the basis...Full Text Available

1995-01-01

Ia-antigen-T-cell interactions for a thymus-independent antigen composed of D amino acids.

BackgroundSensitization to house dust mite allergens is strongly correlated with asthma. Der p 7 elicits strong IgE antibody and T-cell responses in mite allergic...Full Text Available

2010-04-01

Evaluation of Two Homologous Proline-Rich Proteins of Coccidioides posadasii as Candidate Vaccines against Coccidioidomycosis?

Synthetic polypeptide antigens of L amino acids, although bearing repeating sequences, are thymus-dependent (L-TD), whereas the same polymers composed of D amino acids are thymus-independent (D-TI),...Full Text Available

1993-02-01

Early inflammatory markers in elicitation of allergic contact dermatitis

Evaluation of the protective efficacy of recombinant T-cell-reactive proteins of Coccidioides posadasii in a murine model of coccidioidomycosis has led to the discovery of potential...Full Text Available

2007-12-01

Breakdown of the Blood-Brain Barrier during Tick-Borne Encephalitis in Mice Is Not Dependent on CD8⁺ T-Cells

BackgroundAllergic Contact Dermatitis (ACD) is regarded as a T-cell-mediated delayed-type hypersensitivity reaction. We studied the kinetics of the expression of CS-1 fibronectin,...Full Text Available

Novel Cytotoxic Vectors Based on Adeno-Associated Virus

Tick-borne encephalitis (TBE) virus causes severe encephalitis with serious sequelae in humans. The disease is characterized by fever and debilitating encephalitis that can progress to chronic illness...Full Text Available

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positive primary PymT breast cancer cells in primary co-cultured tumor tissue, suggesting target specificity of

Neuroprotective Effects of Methanol Extracts of Jeju Native Plants on Hydrogen Peroxide-induced Cytotoxicity in SH-SY5Y Human Neuroblastoma Cells

KoreaScience (Korea)

Full Text Available

2007-10-01

Alpha-toxin of Staphylococcus aureus.

Coir fibre toxicity: in vivo and in vitro studies.

Alpha-toxin, the major cytotoxic agent elaborated by Staphylococcus aureus, was the first bacterial exotoxin to be identified as a pore former. The protein is secreted as a single-chain, water-soluble...Full Text Available

1991-12-01

Photobiological activity of marmesin (5-B-hydroxyisopropyl-4-5 dihydrofurocoumarin) in Chinese hamster V79 cells

The biological activity of coir fibre, coir ash and their components were investigated in vitro by measuring the haemolytic activity and macrophage cytotoxicity. In vivo studies carried out by injecting guinea pigs intratracheally with coir fibres resulted in resolving granulomas. The observed haemolytic activity and macrophage cytotoxicity was more marked with coir ash compared with coir fibres. Chemical analysis of coir ash revealed the presence of toxic chemical constituents in appreciable amounts. PMID:6283694

1982-03-01

B chain is a functional subunit of beta-bungarotoxin for inducing apoptotic death of human neuroblastoma SK-N-SH cells.

Marmesin was isolated from the medicinal plant, Afraegle paniculata. Its cytotoxicity and mutagenicity in Chinese hamster V79 cells when sensitized to near ultraviolet (NUV) and long wavelength ultraviolet light or black light (BL) were assayed. Marmesin was extremely cytotoxic in the dark. This cytotoxicity was photoenhanced in NUV and BL; the photoenhanced lethality being higher in NUV than in BL. The LD/sub 50/ of marmesin under NUV and BL photosensitization were 0.002 ..mu..M and (0.012 ..mu..M), respectively. In the absence of NUV and BL, marmesin's LD/sub 50/ was 0.013 ..mu..M.NUV and BL without marmesin were not significantly cytotoxic at the fluence rates of 0.29 W/m/sup 2/ and 4.2 W/m/sup 2/, respectively, for up to 20 min. In contrast to the observed high cytotoxicity of marmesin, its mutagenicity at the HGPRT locus (Asub(z)Gsup(r)) was weak. The implication of ...

1983-10-01

Strategies to optimize the outcome of children given T-cell depleted HLA-haploidentical hematopoietic stem cell transplantation

beta-Bungarotoxin (beta-Bgt), a presynaptic phospholipase A(2) (PLA(2)) neurotoxin isolated from the venom of Bungarus multicinctus, consists of A chain and B chain. The goal of the present study is to explore the functional contribution of the two subunits to the toxicity of beta-Bgt. beta-Bgt was found to induce apoptotic death of SK-N-SH cells via elevating intracellular Ca(2+) and intracellular ROS production. Moreover, an activation of p38 MAPK was associated with the cytotoxicity of beta-Bgt. SB202190 (p38 MAPK inhibitor), N-acetylcysteine (antioxidant reagent), 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid (BAPTA) (Ca(2+) chelator) and the inhibitors of Ca(2+) release from intracellular depots (ruthenium red and 2-aminoethoxydiphenyl borate) effectively attenuated the cytotoxicity of beta-Bgt. In sharp contrast to the inability of A chain, B chain was able to induce cytotoxic effects on SK-N-SH cells as ...

2007-10-13

British Library Electronic Table of Contents (United Kingdom)

The most advanced frontier of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is represented by the use of an HLA-partially matched relative as donor. In this type of transplantation, donor-derived natural killer (NK) cells, which are alloreactive towardtoward recipient cells, significantly contribute to the eradication of leukemia blasts. Alloreactive NK cells may also kill host dendritic cells and T lymphocytes, thus preventing graft-versus-host disease and graft rejection, respectively. Sophisticated strategies of adoptive infusion of T-cell lines/clones specific for the most life-threatening pathogens (namely cytomegalovirus, Epstein-Barr virus, Aspergillus and Adenovirus) have been envisaged, and successfully tested in a few pilot trials, to protect the recipient in the...

2011-01-01

Identification of a functional nuclear export signal in the green fluorescent protein asFP499

Herpesvirus saimiri infection of rhesus macaques: A model for acute rhadinovirus-induced t-cell transformation and oncogenesis

The green fluorescent protein (GFP) asFP499 from Anemonia sulcata is a distant homologue of the GFP from Aequorea victoria. We cloned the asFP499 gene into a mammalian expression vector and showed that this protein was expressed in the human lymphoblast cell line Ramos RA1 and in the embryonic kidney 293T cell line (HEK 293T). In HEK 293T cells, asFP499 was localized mainly in the cytoplasm, suggesting that the protein was excluded from the nucleus. We identified _1_9_4LRMEKLNI_2_0_1 as a candidate nuclear export signal in asFP499 and mutated the isoleucine at position 201 to an alanine. Unlike the wildtype form, the mutant protein was distributed throughout the cytoplasm and nucleus. This is First report of a GFP that contains a functional NES.

2006-04-21

British Library Electronic Table of Contents (United Kingdom)

Abstract Herpesvirus saimiri (HVS) causes acute lymphoma and leukemia upon experimental infection of various monkey species. HVS strain C488 is also capable of transforming human T-lymphocytes to stable growth in culture. The most susceptible species for oncogenesis are New World primates, in particular the cottontop tamarin (Saguinus oedipus). However, Old World monkeys such as macaques are the most used animal model for the close-to-human situation. The limited data on HVS infection in Old World monkeys prompted us to investigate susceptibility to infection and disease induction by HVS in macaques. After having established that rhesus macaques can be infected productively, and that rhesus T-cells can be transformed in vivo by HVS, we observed induction of lymphoma in all inoculated anima...

2011-01-01

Low cytotoxicity effect of dendrosome as an efficient carrier for rotavirus VP2 gene transferring into a human lung cell line

British Library Electronic Table of Contents (United Kingdom)

The efficiency of dendrosome (a gene porter) was assessed in transferring recombinant human rotavirus VP2 cDNA into A549, a human lung cell line. After gene transferring, transmission electron microscopy showed core-like particles (CLPs) formation in the transfected cells both with dendrosome and lipofectamine porters. In addition, western blotting analysis showed that the expression of VP2 gene was almost equal in the dendrosome and lipofectamine-transfected cells. Also, the cytotoxicity studies revealed that dendrosome had a lower cytotoxicity than lipofectamine. Therefore, our study may introduce dendrosome as a possible carrier for gene transferring into the human lung cell line, especially, for intranasally administration of DNA vaccines.

2009-01-01

Regulatory compliance | Mott MacDonald

Wastenet

...broad range of experience in designing and building research and development laboratories for products such as vaccines, blood and sera, biological products, medical devices, solid dosage forms , highly potent products and cytotoxic material. We also have experience in a range of modular laboratories for TSE research, ...

Osteoblast response to dimethacrylate composites varying in composition, conversion and roughness using a combinatorial approach

Novel platinum(II) complexes of long chain aliphatic diamine ligands with oxalato as the leaving group: Comparative cytotoxic activity relative to chloride precursors

Dimethacrylate polymers and composites are seeing increased usage in orthopedics. As these applications require the material to integrate with the surrounding tissues, direct contact cytotoxicity...Full Text Available

2009-09-01

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Non-cytotoxic, In Situ Gelable Hydrogels Composed of N-carboxyethyl Chitosan and Oxidized Dextran

Platinum complexes play an important role in the development of anticancer drugs. Their cytotoxicity can be influenced by the nature of the leaving ligands, due to the hydrolysis reaction that occurs prior to the binding of the platinum complex to DNA. Also, non-leaving groups such as lipophilic diamines may affect cellular uptake. In this work, we describe the synthesis of platinum(II) complexes having oxalato and long chain aliphatic N-alkyl ethylenediamines as ligands. The products were characterized by elemental analyses, infrared spectroscopy and {sup 1}H, {sup 13}C and {sup 195}Pt NMR spectroscopy. Biological activity was assessed against tumor cell lines (A{sub 549}, B16-F1, B16-F10, MDA-MB-231) and non-tumor cell lines (BHK-21 and CHO). The length of the carbon chain affects the cytotoxicity and the oxalato complexes were less cytotoxic than the respective chloride-containing analogues. (author)

2010-07-01

Mechanism of cell death resulting from DNA interstrand cross-linking in mammalian cells

A series of in situ gelable hydrogels were prepared from oxidized dextran (Odex) and N-carboxyethyl chitosan (CEC) without any extraneous crosslinking agent. The gelation readily...Full Text Available

2008-10-01

Malignant Catarrhal Fever of Cattle Is Associated with Low Abundance of IL-2 Transcript and a Predominantly Latent Profile of Ovine Herpesvirus 2 Gene Expression

DNA interstrand cross-links (ICLs) are critical cytotoxic lesions produced by cancer chemotherapeutic agents such as the nitrogen mustards and platinum drugs; however, the exact mechanism of ICL-induced...Full Text Available

2011-08-01

Identification of Genes Affecting the Toxicity of Anti-Cancer Drug Bortezomib by Genome-Wide Screening in S. pombe

BackgroundMalignant catarrhal fever (MCF) is a lethal disease of cattle, characterized by vasculitis, necrosis, and accumulation of activated, dysregulated cytotoxic lymphocytes...Full Text Available

Development and cytotoxicity evaluation of SiAlONs ceramics

Bortezomib/PS-341/Velcade, a proteasome inhibitor, is widely used to treat multiple myeloma. While several mechanisms of the cytotoxicity of the drug were proposed, the actual mechanism remains elusive....Full Text Available

Dengue virus protein recognition by virus-specific murine CD8+ cytotoxic T lymphocytes.

SiAlONs are ceramics with high potential as biomaterials due to their chemical stability, associated with suitable mechanical properties, such as high fracture toughness and fracture resistance. The objective of this work was to investigate the mechanical properties and the cytotoxicity of these ceramic materials. Three different compositions were prepared, using silicon nitride, aluminum nitride and a rare earth oxide mixture as starting powders, yielding Si_3N_4-SiAlON composites or pure SiAlON ceramics, after hot-pressing at 1750 deg. C, for 30 min. The sintered samples were characterized by X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM). Furthermore, hardness and fracture toughness were determined using the Vicker's indentation method. The biological compatibility was evaluated by in vitro cytotoxicity tests. Ceramic with elevated hardness, ranging between 17 and 21 GPa, and high fracture toughness of 5 to 6 MPa ...

2007-01-01

Cytotoxicity of Atriplex confertifolia

The identification of the protein targets for dengue virus-specific T lymphocytes may be useful for planning the development of subunit vaccines against dengue. We studied the recognition by murine...Full Text Available

1993-02-01

Cytoprotective Activity of Glycyrrhizae radix Extract Against Arsenite-induced Cytotoxicity

The search for cancer treatment continues to be a global effort. As part of this global effort, many natural products have been tested against cancer cell lines, mostly from tropically located plants....Full Text Available

2010-01-01

Comparison of a Commercial Multiplex Real-Time PCR to the Cell Cytotoxicity Neutralization Assay for Diagnosis of Clostridium difficile Infections?

Licorice, Glycyrrhizae radix, is one of the herbal medicines in East Asia that has been commonly used for treating various diseases, including stomach disorders. This study investigated...Full Text Available

2008-06-01

Cerebellar cell surface antigens of mouse brain.

A commercial multiplex real-time PCR assay (Cepheid Xpert C. difficile assay) for the diagnosis of Clostridium difficile infection was evaluated. The sensitivity and...Full Text Available

2009-11-01

Capacity of deoxycytidine to selectively antagonize cytotoxicity of 5-halogenated analogs of deoxycytidine without loss of antiherpetic activity.

Reaggregated cells from 6- to 8-day-old mouse cerebella have been used to raise antibodies in rabbits. The interaction of these antibodies with cerebellar cell surface components was assessed by cytotoxicity...Full Text Available

1975-10-01

Activation of Cytotoxic and Regulatory Functions of NK Cells by Sindbis Viral Vectors

Enzyme kinetic studies from this laboratory (M. Dobersen and S. Greer, Biochemistry 17:920-928, 1978) suggested that deoxycytidine could antagonize the toxicity of 5-halogenated analogs of deoxycytidine...Full Text Available

1982-09-01

Ab binding alters gene expression in Cryptococcus neoformans and directly modulates fungal metabolism

Oncolytic viruses (OVs) represent a relatively novel anti-cancer modality. Like other new cancer treatments, effective OV therapy will likely require combination with conventional treatments. In order...Full Text Available

A Substructure Combination Strategy to Create Potent and Selective Transthyretin Kinetic Stabilizers that Prevent Amyloidogenesis and Cytotoxicity

Abs facilitate humoral immunity via the classical mechanisms of opsonization, complement activation, Ab-dependent cellular cytotoxicity, and toxin/viral neutralization. There is also evidence that some...Full Text Available

2010-04-01

A Humanin Derivative Reduces Amyloid Beta Accumulation and Ameliorates Memory Deficit in Triple Transgenic Mice

Transthyretin aggregation-associated proteotoxicity appears to cause several human amyloid diseases. Rate-limiting tetramer dissociation and monomer misfolding of transthyretin (TTR) occur before...Full Text Available

2010-02-03

Viral suppression of multiple escape mutants by de novo CD8⁺T cell responses in a human immunodeficiency virus-1 Infected elite suppressor

Humanin (HN), a 24-residue peptide, was identified as a novel neuroprotective factor and shows anti-cell death activity against a wide spectrum of Alzheimer's disease (AD)-related cytotoxicities, including...Full Text Available

Vaccination response to tetanus toxoid and 23-valent pneumococcal vaccines following administration of a single dose of abatacept: a randomized, open-label, parallel group study in healthy subjects

Elite suppressors or controllers (ES) are HIV-1 infected patients who maintain undetectable viral loads without treatment. While HLA-B*57-positive ES are usually infected with virus that is unmutated...Full Text Available

SIV antigen immunization induces transient antigen-specific T cell responses and selectively activates viral replication in draining lymph nodes in retroviral suppressed rhesus macaques

The effect of abatacept, a selective T-cell co-stimulation modulator, on vaccination has not been previously investigated. In this open-label, single-dose, randomized, parallel-group, controlled study,...Full Text Available

2007-01-01

Mapping of TH1 helper T-cell epitopes on major secreted mycobacterial antigen 85A in mice infected with live Mycobacterium bovis BCG.

BackgroundHIV infection causes a qualitative and quantitative loss of CD4⁺T cell immunity. The institution of anti-retroviral therapy (ART) restores CD4⁺T...Full Text Available

Long-Term Specific Immune Responses Induced in Humans by a Human Immunodeficiency Virus Type 1 Lipopeptide Vaccine: Characterization of CD8⁺-T-Cell Epitopes Recognized

TH1 cytokine secretion was examined in response to synthetic peptides of the 85A component of the major secreted, fibronectin-binding antigen 85 complex from Mycobacterium tuberculosis in seven different...Full Text Available

1994-02-01

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Helper T-Cell Epitopes Encoded by the Babesia bigemina rap-1 Gene Family in the Constant and Variant Domains Are Conserved among Parasite Strains

We studied the effect of booster injections and the long-term immune response after injections of an anti-human immunodeficiency virus type 1 (HIV-1) lipopeptide vaccine. This vaccine was injected alone...Full Text Available

2003-10-01

Extracorporeal Photochemotherapy as a Challenging Treatment for Cutaneous T-Cell Lymphoma, Acute and Chronic Graft-versus-Host Disease, Organ Rejection and T-Lymphocyte-Mediated Autoimmune Diseases

Among important candidates for babesial vaccines are apical complex proteins, including rhoptry-associated protein 1 (RAP-1) from Babesia bovis and B. bigemina, which...Full Text Available

1998-04-01

Differentiation associated regulation of microRNA expression in vivo in human CD8⁺T cell subsets

Summary20 years ago, in 1987, Edelson and co-workers published their first report on the effectiveness of a new procedure, called extracorporeal photochemotherapy (ECP), in patients...Full Text Available

2008-01-01

Differential Specificity and Immunogenicity of Adenovirus Type 5 Neutralizing Antibodies Elicited by Natural Infection or Immunization?

BackgroundThe differentiation of CD8⁺T lymphocytes following priming of naïve cells is central in the establishment of the adaptive immune response. Yet, the...Full Text Available

CD5 Is Dissociated from the B-Cell Receptor in B Cells from Bovine Leukemia Virus-Infected, Persistently Lymphocytotic Cattle: Consequences to B-Cell Receptor-Mediated Apoptosis

A recent clinical trial of a T-cell-based AIDS vaccine delivered with recombinant adenovirus type 5 (rAd5) vectors showed no efficacy in lowering viral load and was associated with increased risk of...Full Text Available

2010-01-01

Diffusion-weighted MRI suggests the coexistence of cytotoxic and vasogenic oedema in a case of deep cerebral venous thrombosis

Bovine leukemia virus (BLV), a retrovirus related to human T-cell leukemia virus types 1 and 2, can induce persistent nonneoplastic expansion of the CD5⁺ B-cell population, termed...Full Text Available

2001-02-01

Oleuropein aglycon prevents cytotoxic amyloid aggregation of human amylin.

We report a 20-year-old woman who suffered headaches before presenting with a state of fluctuating vigilance. MRI showed diffuse high signal in the basal ganglia bilaterally on diffusion- and T2-weighted images, which had areas of both low and high apparent diffusion coefficient, presumed to correspond to cytotoxic and vasogenic oedema. MR venography showed no flow in the deep cerebral veins or straight sinus. Heparin was given, with clinical recovery. On follow-up MRI, the appearances became normal. (orig.)

2000-10-01

In vitro toxicity of silica nanoparticles in human lung cancer cells

Pancreatic amyloid deposits of amylin are a hallmark of Type II diabetes and considerable evidence indicates that amylin oligomers are cytotoxic to beta-cells. Many efforts are presently spent to find out naturally occurring molecules, or to design synthetic ones, able to hinder amylin aggregation or to protect cells against aggregate cytotoxicity. In this context, a protective effect of some polyphenols against amyloid cytotoxicity was reported. Actually dietary polyphenols are endowed with multiple health benefits, and extra virgin olive oil is attracting increasing interest as a source of these substances. Here, we investigated the effects on amylin aggregation and cytotoxicity of the secoiridoid oleuropein aglycon, the main phenolic component of extra virgin olive oil. We found that oleuropein, when present during the aggregation of amylin, consistently prevented its ...

2009-07-18

Genotoxicity of 2-alkylcyclobutanones, markers for an irradiation treatment in fat-containing food--Part I: cyto- and genotoxic potential of 2-tetradecylcyclobutanone

The cytotoxicity of 15-nm and 46-nm silica nanoparticles was investigated by using crystalline silica (Min-U-Sil 5) as a positive control in cultured human bronchoalveolar carcinoma-derived cells. Exposure to 15-nm or 46-nm SiO_2 nanoparticles for 48 h at dosage levels between 10 and 100 #mu#g/ml decreased cell viability in a dose-dependent manner. Both SiO_2 nanoparticles were more cytotoxic than Min-U-Sil 5; however, the cytotoxicities of 15-nm and 46-nm silica nanoparticles were not significantly different. The 15-nm SiO_2 nanoparticles were used to determine time-dependent cytotoxicity and oxidative stress responses. Cell viability decreased significantly as a function of both nanoparticle dosage (10-100 #mu#g/ml) and exposure time (24 h, 48 h, and 72 h). Indicators of oxidative stress and cytotoxicity, including total reactive oxygen species (ROS), glutathione, malondialdehyde, ...

2006-12-15

Cytotoxic evaluation of N-isopropylacrylamide monomers and temperature-sensitive poly(N-isopropylacrylamide) nanoparticles

Previous experiments had indicated a slight genotoxic potential both in rat and in human colon cells of a sample of 2-dodecylcyclobutanone, a compound formed by irradiation of food containing palmitic acid in its triglycerides. Up to date, there is no evidence that 2-alkylcyclobutanones occur in non-irradiated foodstuffs, consequently it is prudent to test several members of the class of 2-alkylcyclobutanones which are produced by treatment of fat-containing food with ionising radiation. In this work, 2-tetradecylcyclobutanone (derived from stearic acid) has been tested for its cytotoxic and genotoxic potential. Human colon tumor cell lines, i.e. HT 29 and HT 29 clone 19A, were employed as models for in vitro experiments for cytotoxicity and genotoxicity tests. Cytotoxicity was measured by tetrazolium salt reduction assays (MTT and WST-1) and genotoxicity by determining DNA damage using the Comet Assay. Neither ...

2002-03-01

Total skin electron beam and total nodal irradiation for treatment of patients with cutaneous T-cell lymphoma

The objective of this research project is to investigate the biocompatibility of N-isopropylacrylamide (NIPAAm) monomers and poly(N-isopropylacrylamide) (PNIPAAm) nanoparticles in vitro. PNIPAAm nanoparticles of different sizes were synthesized and characterized by transmission electron microscopy and dynamic light scattering. Cytotoxicity studies using MTS assays were conducted on fibroblasts, smooth muscle cells, and endothelial cells. In addition, the concentration of NIPAAm monomers remaining on PNIPAAm nanoparticles was determined using bromination and spectrophotometry. The cytotoxicity results did not show a significant difference in cell survival when cells were exposed to different particle sizes (100, 300, and 500 nm). Dose studies showed that all three cell types exposed to 100 nm PNIPAAm nanoparticles at concentrations less than or equal to 5 mg/mL were compatible, while cells exposed to NIPAAm monomers exhibited toxicity even at ...

2009-08-15

Human T-cell lymphotropic virus type III infection of the central nervous system: a preliminary in situ analysis

Sixteen patients with advanced cutaneous T-cell lymphoma (CTCL) with or without lymph node involvement, but without evidence of extranodal manifestations, were treated with a combination of total skin electron beam therapy (TSEB) and total nodal irradiation (TNI). Fourteen (87%) patients achieved a complete response (CR) lasting from 1 to 84+ months (median, 8+ months) from the completion of treatment. The best results occurred in 6 patients with pretumorous intracutaneous CTCL (Stages IB and IIA) where the CR has lasted in all patients from 8 to 84+ months (median about 27+ months). Radiotherapy was well tolerated with the major toxicity being bone marrow suppression. The authors conclude that combined TSEB and TNI is a relatively safe and effective treatment for patients with CTCL prior to the development of lymph node involvement. Long-term follow-up is needed to assess the curative potential of this treatment.

1985-06-01

Dual-field rotational (DFR) technique for total-skin electron-beam therapy (TSEBT)

Patients with acquired immunodeficiency syndrome (AIDS) are subject to a spectrum of central nervous system (CNS) disorders. Recent evidence implicates the human T-cell lymphotropic virus type III (HTLV-III) in the pathogenesis of some of these illnesses, although the cells infected by the virus have yet to be identified. Using in situ hybridization, the authors examined brain tissue from two patients with AIDS encephalopathy for the presence of HTLV-III RNA. In both cases, viral RNA was detected and concentrated in, though not limited to, the white matter. The CNS cells most frequently infected included macrophages, pleomorphic microglia, and multinucleated giant cells. Less frequently, cells morphologically consistent with astrocytes, oligodendroglia, and rarely neurons were also infected. The findings strengthen the association of HTLV-III with the pathogenesis of AIDS encephalopathy. In situ hybridization can be applied to routinely prepared biopsy tissue in ...

1986-11-07

Liposome encapsulation of lipophilic N-alkyl-propanediamine platinum complexes: impact on their cytotoxic activity and influence of the carbon chain length

Comparison of dosimetry measured in a noncylindrical Rando-Alderson phantom by two-field, four-field, and six-field total-skin electron-beam therapy (TSEBT) techniques with our dual-field rotational (DFR) technique reveals a superior dosimetry for the latter. Our technique of dual-field rotational DFR-TSEBT is described in detail, and its advantages and indications for the primary management of cutaneous T-cell lymphoma (CTCL) and Kaposi's sarcoma (KS) are discussed.

1987-08-01

Genetical approach to oxygen toxicity. [Saccharomyces cerevisiae

Antitumor platinum(II) complexes derived from N-alkyl-propanediamine differing in the length of their carbon chain (C8, C10, C12 and C14) were incorporated in liposomes and the cytotoxic activity of these formulations was evaluated against tumor (A{sub 549}, MDA-MB-231, B16-F1 and B16-F10) and non-tumor (BHK-21 and CHO) cell lines. Stable and monodisperse liposome suspensions incorporating the platinum complexes were obtained from the lipid composition consisting of distearoyl-sn-glycero-3-phosphocholine, cholesterol and 1,2-distearoyl-sn-glycero- 3-phosphoethanolamine-N-(methoxy(polyethylene glycol)-2000) at 5:3:0.3 molar ratio. The entrapment efficiency (EE%) of the platinum complexes in liposomes increased with the carbon chain length. EE% was higher than 80% in C12- and C14-derivatives. The effect of liposome encapsulation on the cytotoxic activity of the complexes was found to depend on the carbon chain length. These data indicate that the ...

2010-07-01

Evaluation of heavy-metal ion toxicity in fish cells using a combined stress protein and cytotoxicity assay

The role of intermediate products of dioxygen reduction in cytotoxic effects ascribed to oxygen molecules was studied in vivo using various yeast mutants with changed response to oxygen stress. It has been documented that superoxide radical exerts its deleterious effects on yeast cells directly and the role of other oxygen species derived from it is hardly detectable. Yeast Saccharomyces cerevisiae, however, cannot be considered as a typical eukaryotic organism due to its inability of synthesizing polyunsaturated fatty acids (pufa). These fatty acids are known as main target molecules during oxidative stress and their peroxidation leads to cytotoxic effects. As fatty acid content could be easily manipulated in yeast, this organism was used to evaluate the contribution of pufa peroxidation process to the cytotoxic effects of oxygen. Results obtained show, that yeast cells containing linolenic acid as the main constituent of ...

1986-01-01

Enhanced cadmium cytotoxicity in A549 cells with reduced glutathione levels is due to neither enhanced cadmium accumulation nor reduced metallothionein synthesis

All organisms, from bacteria and yeast to humans, respond to physical and chemical stressors by increasing the synthesis of a small group of cellular stress proteins.'' The authors have developed a simple in vitro system for quickly screening environmentally relevant stressors to detect stress-induced proteins that are good candidates for biomarkers. Polyacrylamide gel electrophoresis was used to detect stressor-induced, concentration-dependent changes in cellular stress protein levels in two fish cell culture systems, whereas simultaneous in vitro neutral red uptake cytotoxicity assays measured the stressors effect on cellular physiology. There was a direct concentration-dependent relationship between sublethal cytotoxic effects and the increases in stress protein levels. Increases of 50 to 200% were detected in stress proteins from desert topminnow, Poeciliopsis lucida, hepatoma-derived cell cultures exposed to cadmium or ...

1994-08-01

Cytotoxic effects of WR-2721 on mouse testicular cells

Glutathione (GSH) depletion sensitizes human lung carcinoma (A549-T27) cells to the cytotoxic effects of Cd++. The effects of GSH depletion on Cd++ accumulation and Cd++-induced metallothionein (MT) content were investigated to determine the possible role of these Cd++ responses in the sensitization process. Cellular GSH was depleted to 20% to 25% of control levels with buthionine sulfoximine (BSO), or diethyl maleate (DEM), respectively. Neither treatment significantly affected Cd++-induced accumulation of exogenous 35s-cysteine into intracellular MT in a dose-dependent fashion. The results indicate that neither enhanced Cd++ accumulation nor reduced MT synthesis plays a primary role in affecting enhanced Cd++ cytotoxicity in A549 cells with reduced GSH levels. Although BSO inhibition of GSH synthesis enhanced MT synthesis, it sensitized the cells to Cd++, which suggests an additive effect of GSH and MT in cadmium cytoprotection. This ...

Cytotoxic Naphtho--pyrones from the Mangrove Endophytic Fungus Aspergillus tubingensis (GX1-5E)

WR-2721 (S-2-(3-aminopropylamino)ethylphosphorothioic acid) has been demonstrated to be cytotoxic to stem spermatogonia in the mouse. Five and 10 injections of 300 mg/kg killed sufficient numbers of stem cells to reduce sperm production 56 days after treatment by 16 and 43%, respectively. Single injections of 300 or 400 mg/kg of WR-2721 given 15 min after irradiation produced negligible toxicity to stem cells as measured by counts of repopulated tubules; 600 mg/kg reduced stem cell survival by 47%. Four daily injections of 300 mg/kg given 4, 3, 2, and 1 days prior to irradiation reduced stem cell survival by about 60%. The cytotoxic effects of WR-2721 on testicular stem cells at least partially explains the reduced protection factors observed in the testis with low doses of radiation and during fractionated treatments involving multiple injections of drug.

1984-09-01

British Library Electronic Table of Contents (United Kingdom)

Abstract Four new dimeric naphtho--pyrones, named rubasperone D (1), rubasperone E (2), rubasperone F (3), and its atropisomer rubasperone G (4), together with four known monomeric naphtho--pyrones, TMC 256 A1 (5), rubrofusarin B (6), fonsecin (7), and flavasperone (8), were isolated from the mangrove endophytic fungus Aspergillus tubingensis (GX1-5E) cultivated in solid rice medium. Their structures were elucidated by spectroscopic methods, including IR, 1D- and 2D-NMR, and MS. In the in vitro cytotoxicity assays, 5 displayed inhibitory activities against tumor cell lines of MCF-7, MDA-MB-435, Hep3B, Huh7, SNB19, and U87-MG with IC50 values between 19.92 and 47.98-M. Compounds 1, 6, and 8 also showed mild cytotoxic activity.

2011-01-01

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Expression of bacterial luciferase in eukaryotic cells

Preparation of biodegradable PLA/PLGA membranes with PGA mesh and their application for periodontal guided tissue regeneration

Expression of Bacterial luciferase enzyme (lux) in mammalian cells would be a powerful bioreporter protein system for in vivo imaging because eukaryotic luciferases need expensive substrates. However, only a few efforts have been made to express bacterial luciferase enzyme in mammalian cells. As the result of this, we attempted to construct bicistronic vector including two bacterial luciferase genes (LuxA and LuxB) for assessing the potential to be visualized in vitro or in vivo by optical imaging system after transfection to mammalian cells. We designed and synthesized luxA and luxB genes from Photorhabdus Luminescens. To co-express both luxA and luxB genes from a single promoter, we cloned as a bicistronic transcript fused with an internal ribosomal entry site (IRES). This bicistronic transcript was transfected by Superfect to HEK 293T cell line. We also transfected lux A and lux B vector to HEK 293T ...

2005-11-18

Non-toxigenic Clostridium sordellii: Clinical and microbiological features of a case of cholangitis-associated bacteremia

A biodegradable polylactic acid (PLA)/poly(glycolide-co-lactide) copolymer (PLGA) membrane with polyglycolic acid (PGA) mesh was prepared to aid the effective regeneration of defective periodontal tissues. The microporous membrane used in this study consists of biodegradable polymers, and seems to have a structure to provide appropriate properties for periodontal tissue regeneration. Based on the albumin permeation test, it is known that the biodegradable membrane exhibits the suitable permeability of nutrients. The membrane maintained its physical integrity for 6-8 weeks, which could be sufficient to retain space in the periodontal pocket. Cell attachment and cytotoxicity tests were performed with respect to the evaluation of biocompatibility of the membrane. As a result, the membrane did not show any cytotoxicity. The safety and therapeutic efficacies of the biodegradable membranes were confirmed in animal tests.

2009-10-01

British Library Electronic Table of Contents (United Kingdom)

Toxigenic Clostridium sordellii strains are increasingly recognized to cause highly lethal infections in humans that are typified by a toxic shock syndrome (TSS). Two glucosylating toxins, lethal toxin (TcsL) and hemorrhagic toxin (TcsH) are believed to be important in the pathogenesis of TSS. While non-toxigenic strains of C. sordellii demonstrate reduced cytotoxicity in vitro and lower virulence in animal models of infection, there are few data regarding their behavior in humans. Here we report a non-TSS C. sordellii infection in the context of a polymicrobial bacterial cholangitis. The C. sordellii strain associated with this infection did not carry either the TcsL-encoding tcsL gene or the tcsH gene for TcsH. In addition, the strain was neither cytotoxic in vitro nor lethal in a murine...

2011-01-01

In vitro evaluation of mineral cytotoxicity and inflammatory activity

Cancer-cell-specific cytotoxicity of non-oxidized iron elements in iron core-gold shell NPs

Health risks associated with inhalation of mineral dusts have been identified to a great extent through epidemiology studies, but also have been assessed by conducting subchronic and chronic inhalation studies typically on rodents. However, in vivo studies are softly, time-consuming, requiring complex technologies, and may not yield information on cellular and molecular mechanisms of response. As a result, the use of in vitro cell culture systems has played an important role in studying the toxicology of mineral dusts and providing insight into action mechanisms. This article reviews selected in vitro approaches that are used to investigate the cytotoxic and inflammatory properties of mineral particles and fibers. In addition key findings as they relate to understanding the toxicology of mineral dusts are presented. 165 refs., 1 fig., 5 tab.

1993-12-31

British Library Electronic Table of Contents (United Kingdom)

Gold-coated iron nanoparticles (NPs) selectively and significantly (P <0.0001) inhibit proliferation of oral- and colorectal-cancer cells in vitro at doses as low as 5 mg/mL, but have little adverse effect on normal healthy control cells. The particle treatment caused delay in cell-cycle progression, especially in the S-phase. There was no significant difference in the NP uptake between cancer and control cells, and cytotoxicity resulted primarily from the iron core, before oxidation, rather than from the Fe ions released from the core. In contrast with magnetic NPs that usually serve as drug carriers, diagnostic probes or hyperthermia media, the iron, before oxidation, in the NPs selectively suppressed cancer cell growth and left healthy control cells unaffected in vitro and in vivo. This...

2011-01-01

Antiprotozoal and cytotoxic activities in vitro of Colombian Annonaceae

British Library Electronic Table of Contents (United Kingdom)

Ethnobotanical and chemotaxonomical studies for antiparasitic activity of Colombian Annonaceae were carried out. In vitro antiprotozoal activity of 36 extracts obtained from six different species was determined against promastigotes of three Leishmania species, epimastigotes of Trypanosoma cruzi and both chloroquine sensitive (F32) and resistant (W2) Plasmodium falciparum. Cytotoxic activity was evaluated in U-937 cells. Active extracts were selected according their selectivity index (SI). Extracts from Annona muricata, Rollinia exsucca, Rollinia pittieri and Xylopia aromatica were active against Leishmania spp. and Trypanosoma cruzi showing IC50 values lower than 25mg/ml. Hexane extract from Rollinia pittieri leaves was the most selective against Trypanosoma cruzi and Leishmania spp. (IS=...

2007-01-01

Studies with 1,2-dithiole-3-thione as a chemoprotector of hydroquinone-induced toxicity to DBA/2-derived bone marrow stromal cells.

Relationship between O6-alkylguanine-DNA alkyltransferase activity and N-methyl-N'-nitro-N-nitrosoguanidine-induced mutation, transformation, and cytotoxicity in C3H/10T1/2 cells expressing exogenous alkyltransferase genes.

Stromal cells from DBA/2 mouse bone marrow have been shown to be susceptible to cytotoxicity induced by several redox-active metabolites of benzene, including hydroquinone (HQ). Treatment with HQ also...Full Text Available

1993-06-01

NPM-ALK and the JunB transcription factor regulate the expression of cytotoxic molecules in ALK-positive, anaplastic large cell lymphoma

While a great deal of evidence has directly implicated the importance of O6-alkylation of guanine in the mutagenicity of alkylating agents, evidence demonstrating the oncogenic potential of this lesion...Full Text Available

1992-12-01

Monoclonal antibodies to ovine SBU-T8 and SBU-T6 bind analogous molecules on bovine lymphocytes.

Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive non-Hodgkin lymphoma of T/null immunophenotype that is most prevalent in children and young adults. The...Full Text Available

2011-02-15

Induction of an abortive and futile DNA repair process in E. coli by the antitumor DNA bifunctional intercalator, ditercalinium: role in polA in death induction.

Monoclonal antibodies (mAb) to ovine T-lymphocyte molecules SBU-T8 (Maddox, Mackay & Brandon, 1985), the cytotoxic T lymphocyte, human CD8 equivalent, and SBU-T6 (Mackay et al., 1985), the immature...Full Text Available

1989-06-01

Biodegradable Tri-Block Copolymer Poly(lactic acid)-poly(ethylene glycol)-poly(l-lysine)(PLA-PEG-PLL) as a Non-Viral Vector to Enhance Gene Transfection

Ditercalinium, an antitumor bifunctional intercalator which forms a high affinity reversible complex with DNA, was found to be specifically cytotoxic for polA and lig7 E. coli strains. In the polA strain,...Full Text Available

1988-02-11

Antitumor and Antiviral Activity of Colombian Medicinal Plant Extracts

Low cytotoxicity and high gene transfection efficiency are critical issues in designing current non-viral gene delivery vectors. The purpose of the present work was to synthesize the novel biodegradable...Full Text Available

Scientific Electronic Library Online (English)

Abstract in english Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity) and antiherpetic activity. MTT (Tetrazolium blue) and Neutral Red colorimetric assays were used to evaluate the reduction of viability of cell cultures in presence and absence of the extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type (more) 2 (HSV-2). The 50% cytotoxic concentration (CC50) and the 50% inhibitory concentration of the viral effect (EC50) for each extract were calculated by linear regression analysis. Extracts from Annona muricata, A. cherimolia and Rollinia membranacea, known for their cytotoxicity were used as positive controls. Likewise, acyclovir and heparin were used as positive controls of antiherpetic activity. Methanolic extract from Annona sp. ...

1999-07-01

AQ4N: an alkylaminoanthraquinone N-oxide showing bioreductive potential and positive interaction with radiation in vivo.

??⁺ T-Lymphocyte Cytotoxicity against Envelope-Expressing Target Cells Is Unique to the Alymphocytic State of Bovine Leukemia Virus Infection in the Natural Host

AQ4N (1,4-bis([2-(dimethylamino-N-oxide)ethyl]amino)5,8-dihydroxy- anthracene-9,10-dione) is a novel alkylaminoanthraquinone N-oxide which, on reduction, forms a stable DNA affinic cytotoxic compound...Full Text Available

1995-07-01

Zebrafish embryo extracts promote sphere-forming abilities of human melanoma cell line

Bovine leukemia virus (BLV) is a complex B-lymphotrophic retrovirus of cattle and the causative agent of enzootic bovine leukosis. Serum antibody in infected animals does not correlate with protection...Full Text Available

2000-09-01

British Library Electronic Table of Contents (United Kingdom)

Sphere-forming abilities in culture condition are considered a hallmark of cancer stem-like cells, which represents tumor cell invasiveness and stem-like characteristics. We aimed to show that the sphere-forming subpopulation of human malignant melanoma cell line WM-266-4 acts differently to zebrafish embryo extracts compared with their bulk counterpart. Spheres were maintained in neural stem cell culture conditions. The embryos of zebrafish at specific developmental stages were collected and the extracts were purified under 100 kDa. Spheres were treated with embyo extracts and proliferation assay and immunocytochemistry were conducted. Spheroid cells expressed nestin and epidermal growth factor receptor (EGFR) but not melanoma antigen recognized by T-cells (MART)1, indicating their stem-l...

2009-01-01

Treatment of hematological malignancies with nonmyeloablative, HLA-haploidentical bone marrow transplantation and high dose, post-transplantation cyclophosphamide

British Library Electronic Table of Contents (United Kingdom)

Hematopoietic stem cell transplantation provides the only potential curative option in many patients with hematological malignancies. Finding a suitably matched donor in a timely manner is often difficult. However, most patients have a partially HLA-mismatched (HLA-haploidentical) first-degree relative readily available. Historically, HLA-haploidentical bone marrow transplantation (BMT) has been considered extremely high risk due to high rates of life-threatening graft-versus-host disease (GVHD) and non-relapse mortality (NRM). Modifications of the stem cell graft, such as T-cell depletion, have resulted in poor rates of engraftment. We have recently completed a phase II clinical trial of nonmyeloablative HLA-haploidentical hematopoietic BMT followed by post-transplantation high-cyclophosp...

2011-01-01

Role of regulatory T cell populations in controlling graft vs host disease

British Library Electronic Table of Contents (United Kingdom)

Immune function is critical in health and disease. The control and regulation of immune reactions is an area of intense investigation that has important implications for allogeneic hematopoietic cell transplantation. Immune reactions are regulated in a number of important ways. Compartmentalization of immune responses and the production of both pro-inflammatory and anti-inflammatory cytokines play a major role. More recently several populations of T cells that regulate immune responses termed regulatory T cells have been identified. This manuscript will focus on CD4^+CD25^+FoxP3^+ natural regulatory T cells (T"r"e"g) and @a@bTCR^+CD4^+NK1.1^+ natural killer T (NK-T) cells which both suppress graft vs host disease but appear to function by distinct mechanisms.

2011-01-01

Nickel induced structural and functional alterations in mouse Leydig cells in vitro

British Library Electronic Table of Contents (United Kingdom)

The present study was aimed at investigating effects of nickel (NiCl2) on secretion of testosterone (T), cell viability, ultrastructure and apoptosis in mouse Leydig cells. Testosterone release was measured after 48h of culture with 15.67, 31.25, 62.5, 125, 250, 500 and 1000mmol/L NiCl2 or without NiCl2 using radioimmunoassay. Cell viability was assessed by a MTT (metabolic activity assay). Quantification of apoptotic cells was performed using TUNEL assay and the ultrastructural changes were analyzed using transmission electron microscopy. The viability was decreased after addition of >=250mmol/L NiCl2. A concentration-dependent depression of T production was observed. The percentage of apoptotic cells was significantly increased only after addition of 125, 250 and 1000mmol/L NiCl2. After ...

2011-01-01

100

Estimates of quantitative genetic parameters of immunological traits in the chicken.

A novel BMT technique for treatment of various currently intractable diseases

Three in vivo assays were used to measure the immunocompetence of chickens in two generations of a selection experiment. The obtained data were used to estimate the variance components for sire and dam for antibody production to Pasteurella multocida and Mycoplasma gallisepticum vaccines, for T-cell-mediated immunity evaluated by a phytohemagglutinin wing web assay, and for clearance of foreign particles from the circulatory system. Heritabilities of and genetic correlations among these immunological traits were calculated from the sire variance components. Heritability estimates of the immunological traits based on the sire component of variance ranged from .06 to .53, and genetic correlations among immunological traits were generally negative. PMID:1956847

1991-10-01

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British Library Electronic Table of Contents (United Kingdom)

A recently-developed BMT method combines a ''Perfusion Method'' (PM) for collecting bone marrow cells (BMCs) with the Intra-Bone Marrow (IBM) injection of BMCs (IBM-BMT). As distinct from the conventional aspiration method (AM), the PM allows rapid (within 1 h) collection of BMCs without T cell contamination (T cells < 10%). Therefore, no GvHD occurs. Moreover, the burden on donors, such as back pain, bleeding and infection, can be reduced. Full chimerism can be achieved even with only mild conditioning regimens if IBM-BMT is carried out, since IBM-BMT replaces not only the recipient's hemopoietic stem cells (HSCs) but also mesenchymal stem cells (MSCs) with donor-derived HSCs and MSCs. Using this method, we show that most currently intractable diseases are HSC or MSC disorders, and that t...

2011-01-01

102

Structure determination and investigation on cytotoxicity of potassium dichlorido(l-prolinato)platinate(II) versus chlorido(dimethyl sulfoxide)(l-prolinato)platinum(II) complex -In vitro antitumor deactivation by Cl^-/dmso ligand exchange

British Library Electronic Table of Contents (United Kingdom)

Potassium dichlorido(l-prolinato)platinate(II), K[PtCl"2(l-pro"?"H)] (1), and chlorido(dimethyl sulfoxide)(l-prolinato)platinum(II), [PtCl(l-pro"?"H)(dmso)] (2), were synthesized by ligand substitution reactions. Both complexes were characterized by ^1H, ^1^3C, and ^1^9^5Pt NMR spectroscopy, elemental analysis, and HR-ESI-MS. The molecular structures of 1 and 2 were determined by single crystal X-ray diffraction, proving bidentate coordinated l-prolinato ligand and SP-4-4 configuration of 2a. With the help of DFT calculations stability of possible isomers of 1 and 2 was studied. A considerable difference in the in vitro cytotoxicity of 1 versus 2a (exchange of one chlorido ligand by dmso) against four human cancer cell lines was found.

2011-01-01

103

Stereospecific ligands and their complexes. Part VII. Synthesis, characterization and in vitro antitumoral activity of platinum(II) complexes with O,Oprime-dialkyl esters of (S,S)-ethylenediamine-N,Nprime-di-2-(4-methyl)pentanoic acid

British Library Electronic Table of Contents (United Kingdom)

Platinum(II) complexes (1-4) with bidentate N,Nprime-ligands, O,Oprime-dialkyl esters (alkyl = ethyl, n-propyl, n-butyl and n-pentyl), of (S,S)-ethylenediamine-N,Nprime-di-2-(4-methyl)pentanoic acid were synthesized and characterized by IR, 1H NMR and 13C NMR spectroscopy and elemental analysis. DFT calculations were performed for the complexes and it was found that only one diastereoisomer could be formed. Cytotoxic activity of complexes 1-4 was determined against chronic lymphocytic leukemia cells (CLL) and compared to the activity of ligand precursors L12HCl-L42HCl and corresponding palladium(II) complexes, [PdCl2L] (L = L1-L4). The complexes were found to exhibit significantly higher antitumor activities than cisplatin on CLL cells. Cytotoxic effect of platinum(II) complexes on CLL cel...

2011-01-01

104

Cellular uptake of Aib-containing amphipathic helix peptide.

Biological Research for Radiation Protection

Cell-penetrating peptides (CPPs) are useful tools for the delivery of hydrophilic bioactive molecules, such as peptides, proteins, and oligonucleotides, across the cell membrane. To realize the delivery of therapeutic macromolecules by CPPs, the CPPs are required to show resistance to protease and no cytotoxicity. In order to produce potent non-toxic and protease-resistant CPPs with high cellular uptake, we designed an amphipathic helix peptide using ?-aminoisobutyric acid (Aib, U) and named it MAP(Aib). In the MAP(Aib) molecule, five Aib residues are aligned on the hydrophobic face of the helix and five lysine (K) residues are aligned on the hydrophilic face. MAP(Aib) showed potent resistance to trypsin and pronase compared with MAP, an amphipathic helix peptide formed by usual amino acids. Fluorescein-labeled MAP(Aib) efficiently traversed the A549 cell membrane, diffusing into the cytoplasm and slightly into the nucleus without exerting any ...

2011-08-11

105

A DC-81-indole conjugate agent suppresses melanoma A375 cell migration partially via interrupting VEGF production and stromal cell-derived factor-1a-mediated signaling

The work scope of 'Biological Research for the Radiation Protection' had contained the research about ornithine decarboxylase and its controlling proteins, thioredoxin, peroxiredoxin, S-adenosymethionine decarboxylase, and glutamate decarboxylase 67KD effect on the cell death triggered ionizing radiation and H_2O_2(toxic agents). In this study, to elucidate the role of these proteins in the ionizing radiation (or H_2O_2)-induced apoptotic cell death, we utilized sensesed (or antisensed) cells, which overexpress (or down-regulate) RNAs associated with these proteins biosynthesis, and investigated the effects of these genes on the cytotoxicity caused by ionizing radiation and H_2O_2(or paraquat). We also investigated whether genisteine(or thiamine) may enhance the cytotoxic efficacy of tumor cells caused by ionizing radiation (may enhance the preventing effect radiation or paraquat-induced damage) because such compounds are able to potentiate the ...

106

British Library Electronic Table of Contents (United Kingdom)

Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) chemicals are antitumor antibiotics inhibiting nucleic acid synthesis. An indole carboxylate-PBD hybrid with six-carbon spacer structure (IN6CPBD) has been previously demonstrated to induce melanoma cell apoptosis and reduce metastasis in mouse lungs. This study aimed at investigating the efficacy of the other hybrid compound with four-carbon spacer (IN4CPBD) and elucidating its anti-metastatic mechanism. Human melanoma A375 cells with IN4CPBD treatment underwent cytotoxicity and apoptosis-associated assays. Transwell migration assay, Western blotting, and ELISA were used for mechanistic study. IN4CPBD exhibited potent melanoma cytotoxicity through interrupting G1/S cell cycle progression, increasing DNA fragmentation and hypodipoidic DNA contents, a...

2011-01-01

107

Silencing of SARS-CoV spike gene by small interfering RNA in HEK 293T cells

Development of radiological emergency preparedness technology

Two candidate small interfering RNAs (siRNAs) corresponding to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike gene were designed and in vitro transcribed to explore the possibility of silencing SARS-CoV S gene. The plasmid pEGFP-optS, which contains the codon-optimized SARS-CoV S gene and expresses spike-EGFP fusion protein (S-EGFP) as silencing target and expressing reporter, was transfected with siRNAs into HEK 293T cells. At various time points of posttransfection, the levels of S-EGFP expression and amounts of spike mRNA transcript were detected by fluorescence microscopy, flow cytometry, Western blot, and real-time quantitative PCR, respectively. The results showed that the cells transfected with pEGFP-optS expressed S-EGFP fusion protein at a higher level compared with those transfected with pEGFP-S, which contains wildtype SARS-CoV spike gene sequence. The green fluorescence, mean fluorescence intensity, and ...

2004-11-26

108

Two new paeciloxocins from a mangrove endophytic fungus Paecilomyces sp.

Large-scale field tracer experiments have been conducted on Ulchin, Wolsung and Daeduk sites for the purpose of validating FADAS and of analyzing the environmental characteristics around the nuclear sites. The most influential factor in atmospheric dispersion is the meteorological condition. During the experiment, meteorological data were measured on the release point and the selected positions among sampling points. Once radioactive materials are released to the atmosphere, members of public may be exposed through the environmental media such as air, soil and foods. Therefore, to protect the public, adequate countermeasures should be taken at due time for those exposure pathways. both processes, of justification and optimization are applied to a countermeasure simultaneously for decision-making. The work scope of Biological research for the radiation protection had contained the search of biological microanalytic methods for assessing the health effect by {gamma}-radiation and toxic ...

2000-04-01

109

British Library Electronic Table of Contents (United Kingdom)

Paeciloxocins A and B (2-(1-hydroxy-3-methylbutyl)- and 2-(1-acetoxy-3-methylbutyl)- 11-hydroxy-9-methyl-1-methoxy-5H,7H-dibenzo[b,g]-1,5-dioxocin-5-ones), viz., two new metabolites, were isolated from the mangrove fungus Paecilomyces sp. collected from the Taiwan Strait. Their structures were elucidated by spectral methods. Paeciloxocin A exhibited strong cytotoxicity against the hepG2 cell line.

2010-01-01

110

Topoisomerases of kinetoplastid parasites: why so fascinating?

British Library Electronic Table of Contents (United Kingdom)

Summary DNA topoisomerases are the key enzymes involved in carrying out high precision DNA transactions inside the cells. However, they are detrimental to the cell when a wide variety of topoisomerase-targeted drugs generate cytotoxic lesions by trapping the enzymes in covalent complexes on the DNA. The discovery of unusual heterodimeric topoisomerase I in kinetoplastid family added a new twist in topoisomerase research related to evolution, functional conservation and their preferential sensitivity to Camptothecin. On the other hand, structural and mechanistic studies on kinetoplastid topoisomerase II delineate some distinguishing features that differentiate the parasitic enzyme from its prokaryotic and eukaryotic counterparts. This review summarizes the recent advances in research in kin...

2006-01-01

111

Synthesis and Biophysical Characterization of Chlorambucil Anticancer Ether Lipid Prodrugs

DEFF Research Database (Denmark)

The synthesis and biophysical characterization of four prodrug ether phospholipid conjugates are described. The lipids are prepared from the anticancer drug chlorambucil and have C16 and C18 ether chains with phosphatidylcholine or phosphatidylglycerol headgroups. All four prodrugs have the ability to form unilamellar liposomes (86-125 nm) and are hydrolyzed by phospholipase A2, resulting in chlorambucil release. Liposomal formulations of prodrug lipids displayed cytotoxicity toward HT-29, MT-3, and ES-2 cancer cell lines in the presence of phospholipase A2, with IC50 values in the 8-36 ?M range.

2009-01-01

112

Solid-phase synthesis and pharmacological evaluation of novel nucleoside-tethered dinuclear platinum(II) complexes

British Library Electronic Table of Contents (United Kingdom)

Three novel inosine-based dinuclear platinum complexes have been synthesized via a solid-phase strategy. In these compounds, the metal is linked both to the N-7 of the purine nucleus and to the terminal amine group of a hexylamine side chain installed on N-1. Cis- or trans- diamine as well as ethylenediamine ligands are coordinated to platinum along with a chloride. The synthesised complexes were tested against four different human tumor cell lines. One of these complexes proved to be more cytotoxic than cisplatin against the MCF7 cancer cell line in a short-term exposure assay.

2011-01-01

113

Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

Surgical adjuvant therapy in colon carcinoma: a human tumor spheroid model for evaluating radiation sensitizing agents

The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of /sup 3/H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes.

1987-11-01

114

Inhalation of tobacco smoke induces increased proliferation of urinary bladder epithelium and endothelium in female C57BL/6 mice

HT-29 human colon tumor cells growing as spheroids have been evaluated as a model system for measuring the response of human colon tumor cell to antineoplastic agents. HT-29 cells have been capacity to form spheroids up to 1 mm or more in diameter when grown in spinner culture. The multicellular HT-29 spheroids develop hypoxic centers reflecting the cellular conditions found in human cancer treatment, i.e., nutritionally deficient hypoxic cells that are felt to be a significant source of both radiation and chemotherapy clinical treatment failures. Spheroids of increasing size were radiated and then dispersed into single cells for colony survival assay. Compared with irradiated single cell suspensions, the spheroid cells demonstrated a significant increase in radioresistance. Growing spheroids developed a complex radiation survival curve which was variable with respect to size of the spheroid. The drug 5-Fu was studied to examine in a preliminary fashion its interaction with these ...

115

A?(1-42) Aggregates into non-Toxic Amyloid Assemblies in the Presence of the Natural Polyphenol Oleuropein Aglycon.

Cigarette smoking is the major environmental risk factor for bladder cancer in humans. Aromatic amines, potent DNA-reactive bladder carcinogens present in cigarette smoke, contribute significantly. However, increased cell proliferation, caused by direct mitogenesis or in response to cytotoxicity, may also play a role since urothelial hyperplasia has been observed in human cigarette smokers. We examined the urothelial effects of cigarette smoke (whole body inhalation exposure (Teague) system) in female C57BL/6 mice at various times in two studies, including reversibility evaluations. In both studies, no urothelial hyperplasia was observed by light microscopy in any group. However, in study 1, the Ki-67 labeling index (LI) of the urothelium was significantly increased in the smoke exposed group compared to controls through 3 months, but was not present at 6, 9 or 12 months even with continued exposures. In the groups that discontinued smoke exposure, it returned to ...

2007-11-20

116

Regulatory role of neuron-restrictive silencing factor in expression of TRPC1

Amyloid aggregation starts with the initial misfolding of peptide/protein precursors, with subsequent structural rearrangement into oligomers and protofibrils; the latter eventually organize into fibrils with shared basic structural features, found deposited in amyloid diseases. Mounting evidence indicates early oligomers as the most toxic amyloid species; accordingly, the search of inhibitors of their growth is considered a promising target to prevent amyloid toxicity. We recently showed that oleuropein aglycon, a polyphenol abundant in the extra virgin olive oil, interferes with the aggregation of amylin (involved in type-2 diabetes), eliminating its cytotoxicity. Here we report that oleuropein aglycon also hinders amyloid aggregation of A?(1-42) and its cytotoxicity, suggesting a general effect of such polyphenol. In particular, by using a wide panel of different spectroscopic, immunologic, cell viability and imaging techniques we provide a ...

2011-05-18

117

Development of radiological emergency preparedness and biological dosimetry technology

Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca"2"+ channel (SOCC)-mediated Ca"2"+ entry. Transfection of TRPC1 into primary cardiomyocytes increased NFAT activity, indicating a major role for TRPC1 in NFAT ...

2006-12-22

118

Detection of constitutive heterodimerization of the integrin Mac-1 subunits by fluorescence resonance energy transfer in living cells

Large-scale field tracer experiments have been conducted on Ulchin and Wolsung nuclear sites for the purpose of validating FADAS and of analyzing the environmental characteristics around the nuclear site. The most influential factor in atmospheric dispersion is the meteorological condition. During the experiment, meteorological data were measured on the release point and the selected positions among sampling points. Once radioactive materials are released to the atmosphere, members of public may be exposed through the environmental media such as air, soil and foods. Therefore, to protect the public, adequate countermeasures should be taken at due time for those exposure pathways. Both processes of justification and optimization are applied to a countermeasure simultaneously for decision-making. The work scope of biological research for the radiation protection had contained the search of biological microanalytic methods for the assessment of health effect by radiation and toxic agents, ...

1999-04-01

119

An evaluation of the pendulum technique of electron beam therapy

Macrophage differentiation antigen associated with complement three receptor function (Mac-1) belongs to #beta#_2 subfamily of integrins that mediate important cell-cell and cell-extracellular matrix interactions. Biochemical studies have indicated that Mac-1 is a constitutive heterodimer in vitro. Here, we detected the heterodimerization of Mac-1 subunits in living cells by means of two fluorescence resonance energy transfer (FRET) techniques (fluorescence microscopy and fluorescence spectroscopy) and our results demonstrated that there is constitutive heterodimerization of the Mac-1 subunits and this constitutive heterodimerization of the Mac-1 subunits is cell-type independent. Through FRET imaging, we found that heterodimers of Mac-1 mainly localized in plasma membrane, perinuclear, and Golgi area in living cells. Furthermore, through analysis of the estimated physical distances between cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP) fused to Mac-1 subunits, we ...

2006-08-04

120

Tumor necrosis factor-? is associated with positive lymph node status in patients with recurrence of colorectal cancer?indications for anti-TNF-? agents in cancer treatment

Electron beam therapy of lesions such as cutaneous metastatic carcinoma and reticulum cell sarcoma is performed via multiple portals for a wide irradiation field. However, the dose distribution in border areas is generally uneven, resulting in hot and cold dose areas depending on the intervals of the portals. We performed electron irradiation by the pendulum technique, especially on curved areas, and evaluated the technique in various respects. Pendulum electron beam irradiation is indicated when the length of the cone must be reduced in order to deliver the target volume near the skin surface as well as to avoid the occurrence of hot spots deep in the body. We prepared a 15cm rotating cone by cutting a 30cm fixed irradiation cone. The modification posed no disadvantages in terms of extent and flatness of the beam, or stability during rotation. After determining the relationship between the rotation speed and the dose, the technique was successfully applied to a patient with adult ...

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121

British Library Electronic Table of Contents (United Kingdom)

Introduction The progressive growth of malignancies is accompanied by a decline in the immune response through mechanisms which are poorly understood. Apoptosis and induction of inflammation by tumor released cytokines as tumor escape mechanisms have been proposed to play an important role in colorectal carcinogenesis. Methods Expression of Tumor necrosis factor-alpha (TNF-?) was analyzed in colorectal cancer specimen and the cancer cell line HT-29 by immunohistochemistry and RT-PCR. TNF-? expression on protein and mRNA level were correlated with clinical characteristics and impact on survival. TNFR-1 was co-labelled with TNF-? and CD8+ cytotoxic T cells in immunofluorescence double staining experiments. Results: 94% (n?=?98/104) of the patients with CRC expressed TNF-?. High TNF-? express...

2011-01-01

122

The expression profile of TLR9 mRNA and CpG ODNs immunostimulatory actions in the teleost gilthead seabream points to a major role of lymphocytes

British Library Electronic Table of Contents (United Kingdom)

Abstract. The potential effects of synthetic unmethylated oligodeoxynucleotides (ODN) containing CpG motifs, mimicking bacterial DNA, has never been evaluated on the immune response in the teleost fish gilthead seabream (Sparus aurata), the most important fish species in Mediterranean aquaculture. First, binding and competition studies have demonstrated that binding is saturated and promiscuous, suggesting the participation of several receptors. Moreover, leucocyte cytotoxic (NCC) activity, production of ROIs (reactive oxygen intermediates), and expression of immune-relevant genes was greatly primed by ODNs. Focusing on the mechanism, the TLR9 gene is widely distributed in seabream tissues and differently regulated in vitro by several stimuli. Moreover, and for the first time in fish, TLR9...

2008-01-01

123

Stress-induced martensitic transformation of metastable #beta#-titanium alloy

Resveratrol Potentiates the Cytotoxic Oxidative Stress Induced by Chemotherapy in Human Colon Cancer Cells

The constituent phases and associated deformed microstructure of the quenched Ti-xNb-(0.5-1.5) at.% Si alloy consisting of non-cytotoxicity elements, where x = 24-30 at.%, were investigated to provide pseudoelasticity for biomedical and sensor applications. Optical microscopy revealed that stress-induced martensitic transformation takes place during the deformation in the present alloys. It is confirmed from the X-ray diffraction results of the deformed specimens that the crystal structure of the stress-induced martensite phase is the orthorhombic so-called #alpha#'' structure. Within the alloys having #beta#(bcc) phase studied Nb-poor region appeared to exhibit a dominant behavior for stress-induced martensitic transformation than Nb-rich region. This result suggests that metastable #beta# phase is superior to stable #beta# phase for the occurrence of stress-induced martensitic transformation in the present alloy system.

2007-03-25

124

British Library Electronic Table of Contents (United Kingdom)

Abstract The treatment of advanced colorectal cancer with 5-fluorouracil has two major problems: development of tumor resistance and toxicity toward normal tissues. The aim of this study was to investigate the possible advantages of combining 5-fluorouracil (5-FU) with resveratrol (trans-3, 4prime, 5-trihydroxystilbene) for treating HT-29 and SW-620 colorectal carcinoma cell lines. Since combined treatment using 5-FU with resveratrol resulted in a significant decrease in long-term cell survival, we investigated the possible basis of this synergistic interaction at a molecular level, focusing on oxidative stress as a possible mediator of cell death. Resveratrol established interactions with the mitochondria of cancer cells and induced an imbalance in cellular antioxidant activities, leading...

2011-01-01

125

Report on NCI symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. II. Cellular and animal models

Premnalatifolin A, a novel dimeric diterpene from Premna latifolia Roxb

The point at which the common final pathway for induction of cancer by chemical carcinogens and ionizing radiation has not been identified. Although common molecular targets are suggested by recent findings about the role of oncogenes, the mechanism by which the deposition of radiation energy and the formation of adducts or other DNA lesions induced by chemicals affects the changes in the relevant targets may be quite different. The damage to DNA that plays no part in the transformation events, but that influences the stability of the genome, and therefore, the probability of subsequent changes that influence tumorigenesis may be more readily induced by some agents than others. Similarly, the degree of cytotoxic effects that disrupt tissue integrity and increase the probability of expression of initiated cells may be dependent on the type of carcinogen. Also, evidence was presented that repair of the initial lesions could be demonstrated after exposure to low-LET ...

1984-05-20

126

British Library Electronic Table of Contents (United Kingdom)

Premnalatifolin A (1), a unique icetexane diterpene dimer was isolated from the stem-bark of Indian medicinal plant, Premna latifolia. Its structure and relative stereochemistry were elucidated on the basis of detailed spectroscopic analysis, including HRESIMS and 2D NMR (COSY, HSQC, HMBC, and NOESY) spectra. The compound has dimeric carbon skeleton composed of two icetexane skeletal diterpenes linked via ether bond. Further, premnalatifolin A (1) was also evaluated for its cytotoxicity against cancer cell lines (HT-29, A-431, MCF-7, Hep-G2, PC-3, A-549, B-16 F10, and ACHN), which displayed potent activity against HT-29 and MCF-7 cell lines with the IC50 values of 12.15 and 1.11mg/mL, respectively.

2011-01-01

127

Ovis aries CR4 is involved in Mannheimia haemolytica leukotoxin-induced cytotoxicity

British Library Electronic Table of Contents (United Kingdom)

Pneumonia caused by Mannheimia haemolytica is an important disease of domestic sheep (DS, Ovis aries) and cattle (BO). M. haemolytica is a normal commensal of the upper respiratory tract in ruminants, but during stress and viral infection it breaches the host innate mucosal defense and descents into lungs causing fibrinous pleuropneumonia. Leukotoxin (Lkt) produced by M. haemolytica is cytolytic to all subsets of ruminant leukocytes. Earlier, we and others have shown that DS and BO LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) can mediate Lkt-induced cytolysis. It is not clear whether CR4 (CD11c/CD18), which is involved in chemotaxis, phagocytosis and regulates host immune response can also mediate Lkt-induced cytolysis in ruminants. The host innate immune response to M. haemolytica is poorly ...

2010-01-01

128

Inflammatory Biomarkers of Sulfur Mustard Analog 2-Chloroethyl Ethyl Sulfide-Induced Skin Injury in SKH-1 Hairless Mice

British Library Electronic Table of Contents (United Kingdom)

Sulfur mustard (HD) is an alkylating and cytotoxic chemical warfare agent, which inflicts severe skin toxicity and an inflammatory response. Effective medical countermeasures against HD-caused skin toxicity are lacking due to limited knowledge of related mechanisms, which is mainly attributed to the requirement of more applicable and efficient animal skin toxicity models. Using a less toxic analog of HD, chloroethyl ethyl sulfide (CEES), we identified quantifiable inflammatory biomarkers of CEES-induced skin injury in dose- (0.05-2 mg) and time- (3-168 h) response experiments, and developed a CEES-induced skin toxicity SKH-1 hairless mouse model. Topical CEES treatment at high doses caused a significant dose-dependent increase in skin bi-fold thickness indicating edema. Histopathological e...

2009-01-01

129

Differential immunotoxic effects of inorganic and organic mercury species in vitro

British Library Electronic Table of Contents (United Kingdom)

Despite the fact that humans are exposed to multiple forms of mercury (elemental, inorganic, and organic), most research on mercury toxicity has focused on methylmercury (MeHg) and on neurotoxic outcomes and mechanisms. Recent work has indicated that the immunotoxic effects of mercury compounds may be significant contributors to human disease as well as mechanistically relevant to other target organ toxicities. In this study, we compared the effects of inorganic Hg (iHg) to organic Hg species (MeHg and ethylmercury, EtHg) in human peripheral blood mononuclear cells (PBMCs) in vitro at sub-cytotoxic concentrations, using methods developed to characterize response of human PBMCs to iHg in vitro. PBMCs were isolated from six volunteer blood donors (three males and three females) and cultured ...

2010-01-01

130

Anthracenedione derivatives as anticancer agents isolated from secondary metabolites of the mangrove endophytic fungi.

A variable gene delivery carrier-biotinylated chitosan/polyethyleneimine

In this article, we report anticancer activity of 14 anthracenedione derivatives separated from the secondary metabolites of the mangrove endophytic fungi Halorosellinia sp. (No. 1403) and Guignardia sp. (No. 4382). Some of them inhibited potently the growth of KB and KBv200 cells, among which compound 6 displayed strong cytotoxicity with IC(50) values of 3.17 and 3.21 microM to KB and KBv200 cells, respectively. Furthermore, we demonstrate that the mechanism involved in the apoptosis induced by compound 6 is probably related to mitochondrial dysfunction. Additionally, the structure-activity relationships of these compounds are discussed. PMID:20479985

2010-04-23

131

A new method for quantifiable and controlled dosage of particulate matter for in vitro studies: The electrostatic particulate dosage and exposure system (EPDExS)

A variable gene delivery system has been developed based on conjugating chitosan to biotin through a functionalized poly(ethylene glycol) (PEG) spacer, which can be used to further bind different molecules on the outer layer of a polymer/DNA complex by streptavidin (SA)-biotin linkage. In this study, TAT-conjugated SA was used as the model molecule to prove the conjugation function of the prepared complex. In addition, low-molecular-weight poly(ethyleneimine) (PEI) was added into the polymer/DNA complex to increase the transfection efficiency. The results of the luciferase assay show that the transfection efficiency of the prepared complex was significantly correlated with the amount of PEI and was further enhanced when TAT was conjugated to the complex by SA-biotin linkage. Considered to have negligible cytotoxic effects, the variable gene delivery complex prepared in this study would be of considerable potential as carriers for in vitro applications.

2010-12-01

132

British Library Electronic Table of Contents (United Kingdom)

An exposure chamber is described for the quantifiable addition of fine and ultrafine aerosol particulate matter directly to cells and used to demonstrate the in vitro cytotoxicity of fine 1,4-naphthoquinone particles to murine lung epithelial cells. The electrostatic particulate dosage and exposure system (EPDExS) operates on the principle of electrostatic precipitation and is shown to deposit fine and ultrafine aerosol particles directly to cells with 100% efficiency for particle diameters in the range of 40-530nm. This range is not limited by the EPDExS, but rather by the aerosolization method used for this study. Numbers of particles deposited onto the cells are counted with a condensation particle counter, negating any need to calculate or estimate particle exposure. The process of par...

2008-01-01

133

A comparison of hepatic in vitro metabolism of T-2 toxin in rats, pigs, chickens, and carp

British Library Electronic Table of Contents (United Kingdom)

T-2 toxin, a highly toxic member of the type-A trichothecenes, is produced by various Fusarium moulds that can potentially affect human health. It is strongly cytotoxic for human hematopoietic progenitors. Alimentary toxic aleukia (ATA), a disease typically associated with human, is primarily induced by T-2 toxin. A comparison of the metabolism of T-2 toxin incubated with hepatocytes of rats, piglets, chickens, and the hepatic subcellular fractions (microsomes and cytosol) of piglets, chickens, rats, and carp (common carp and grass carp) was carried out. The activities of the recombinant pig CYP3A29 on the transformation of T-2 and HT-2 toxins were preliminary studied. Metabolites were identified by novel LC/MS-IT-TOF. Qualitative similarities and differences across the species were observ...

2011-01-01

134

A Hypothesis: Supplementation with Mushroom-Derived Active Compound Modulates Immunity and Increases Survival in Response to Influenza Virus (H1N1) Infection.

Increased oxidative stress and antioxidant expression in mouse keratinocytes following exposure to paraquat

We hypothesize that the mushroom-derived active compound may be a potential strategy for increasing survival in response to influenza virus (H1N1) infection through the stimulation of host innate immune response. The validity of the hypothesis can be tested by immune response to influenza infection as seen through survival percentage, virus clearance, weight loss, natural killer cell cytotoxicity, Tumor Necrosis Factor-? (TNF-?) and Interferon-gamma (IFN-?) levels, lytic efficiency in the spleens of mice and inducible nitric oxide synthase mRNA expressions in RAW 264.7 murine macrophage cells. The hypothesis may improve people's quality of life, reduce the medical cost of our healthcare system and eliminate people's fears of influenza outbreak. PMID:21660092

2011-03-20

135

Effective use of optimized, high-dose (50 kGy) gamma irradiation for pathogen inactivation of human bone allografts.

Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is a widely used herbicide known to induce skin toxicity. This is thought to be due to oxidative stress resulting from the generation of cytotoxic reactive oxygen intermediates (ROI) during paraquat redox cycling. The skin contains a diverse array of antioxidant enzymes which protect against oxidative stress including superoxide dismutase (SOD), catalase, glutathione peroxidase-1 (GPx-1), heme oxygenase-1 (HO-1), metallothionein-2 (MT-2), and glutathione-S-transferases (GST). In the present studies we compared paraquat redox cycling in primary cultures of undifferentiated and differentiated mouse keratinocytes and determined if this was associated with oxidative stress and altered expression of antioxidant enzymes. We found that paraquat readily undergoes redox cycling in both undifferentiated and differentiated keratinocytes, generating superoxide anion and hydrogen peroxide as well as increased protein oxidation which ...

2008-09-15

136

Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-a light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides)

The safety of tissue allografts has come under increased scrutiny due to recent reports of allograft-associated bacterial and viral infections in tissue recipients. We report that 50 kGy of gamma irradiation, nearly three times the dose currently used, is an effective pathogen inactivation method when used under optimized conditions that minimize damage to the tissue. Cancellous bone dowels treated with a radioprotectant solution and 50 kGy of optimized irradiation had an ultimate compressive strength and modulus of elasticity equal to conventionally irradiated (18 kGy) and non-irradiated control bone grafts. We subjected bone dowels treated with this pathogen inactivation method to an in vitro cytotoxicity test using three different mammalian cell lines and concluded that the treated grafts were not cytotoxic. The log reduction of nine pathogens spiked into radioprotectant-treated bone irradiated to 50 kGy was also tested. We achieved 4.9 logs ...

2005-05-01

137

Rapid toxicity testing based on mitochondrial respiratory activity

Purpose: Patients with mycosis fungoides [cutaneous T-cell lymphoma (CTCL)] may benefit from adjuvant therapy after completing total skin electron beam therapy (TSEBT). We report the results for (T1(T2)) CTCL patients treated with adjuvant oral psoralen plus ultraviolet light (PUVA) with respect to overall survival (OS), disease-free survival (DFS), salvage of recurrence, and toxicity. Methods and Materials: Between 1974 and 1993, TSEBT was administered to a total of 213 patients with CTCL. Records were reviewed retrospectively, and a total of 114 patients were identified as having T1 or T2 disease. Radiotherapy was provided via a 6-MeV linac to a total of 36 Gy, 1 Gy/day, 4 days/week, for 9 weeks. Beginning in 1988, patients were offered adjuvant PUVA within 2 months of completing TSEBT. This was started at 0.5-2 J/m"2, 1-2 treatments/week, with a taper over 3-6 months. Therapy then continued once per month. There were 39 T1 and 75 T2 patients. Six T1 (15%) and ...

1997-07-15

138

Primary gonadal damage following treatment of brain tumors in childhood

The need exists for rapid and inexpensive methods to determine the health effects of environmental contaminants on biological systems. One of the current research approaches for assessing cytotoxicity is to monitor the respiratory activity of the mitochondrion, a sensitive, nonspecific subcellular target site. Detected changes in mitochondrial function after the addition of a test chemical could be correlated to toxic effects. Mitochondrial respiration can be characterized by three indices: state 3 and state 4 respiratory rates, and the respiratory control ratio (RCR). State 4, the idle or resting state, results when coupled mitochondrial respire in a medium containing inorganic phosphate and a Kreb's cycle substrate in the absence of a phosphate acceptor such as adenosine diphosphate (ADP). In the presence of ADP the respiration rate increases to a maximum (state 3), accompanied by phosphorylation of ADP to adenosine triphosphate (ATP). The ratio of state ...

1990-05-01

139

Photochemically and Pharmacological studies of Maytenus Frosskaoliana

Gonadal function was studied in two groups of children previously treated for medulloblastoma with surgery followed by postoperative craniospinal irradiation. In group 1 but not in group 2, the children also received adjuvant chemotherapy for one to two years. All children in group 1 received a nitrosourea (BCNU or CCNU), plus vincristine in four and procarbazine in three patients. The nine children in group 1 showed clinical and biochemical evidence of gonadal damage with elevated serum FSH concentrations and, in the boys, small testes for their stage of pubertal development. In group 2 (n . 8), each child had completed pubertal development normally, the boys had adult sized testes and the girls regular menses. Gonadotropin values were normal in all eight children. We conclude that nitrosoureas were responsible for the gonadal damage in the children in group 1, with procarbazine also contributing to the damage in the three children who received this drug. In view of the limited proved ...

1983-10-01

140

New Lactone and Xanthone Derivatives Produced by a Mangrove Endophytic Fungus Phoma sp. SK3RW1M from the South China Sea

Column chromatography of the petroleum ether and chloroformic extracts of Maytenus Forsskaoliana afforded four compounds: friedilin1, B-amyrin 2, B-sitosterol 3 and betulin 4. The structure of these compounds were established on bases of spectral (IR,MS,H and C-NMR)as well as physical data. Antimicrobial activity for extracts indicated weak potency (200ug/ml) while betulin4 showed a pronounced activity (MIC and MBC 20ug/ml).The cytotoxic activity of beutalin4 significantly indicated promising activity (IC50 40ug/ml) on both HeLa and Hep-2 cells. The pharmacological activity of diferent extracts showed sedative effect, slowing respiration, dose -dependent decrease in the arterial blood pressure by 40.1mm Hg (at adose 200mg /kg),decrease in the heart rate 67.3% (at a dose 50mg /kg)and decrease in the body temperature by 4.2C after 2 hrs (at a dose 200mg /kg). (author)

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141

British Library Electronic Table of Contents (United Kingdom)

A new lactone, 1,8-dihydroxy-10-methoxy-3-methyldibenzo[b,e]oxepine-6,11-dione (1), and two new xanthones, 1-hydroxy-8-(hydroxymethyl)-6-methoxy-3-methyl-9H-xanthen-9-one (2) and 1-hydroxy-8-(hydroxymethyl)-3-methoxy-6-methyl-9H-xanthen-9-one (3), were isolated from a mangrove endophytic fungus Phoma sp. SK3RW1M collected from the South China Sea. This is the first report on xanthone derivatives isolated as secondary metabolites from Phoma species. Their structures were elucidated by spectroscopic methods, mainly 1D- and 2D-NMR techniques, and the structure of compound 2 was confirmed by X-ray crystallography. Cytotoxicity assays showed that compounds 1-3 were inactive against KB and KBv200 cells.

2010-01-01

142

In vitro corrosion, cytotoxicity and hemocompatibility of bulk nanocrystalline pure iron

Highly Porous, Water-Soluble, Superparamagnetic, and Biocompatible Magnetite Nanocrystal Clusters for Targeted Drug Delivery.

Bulk nanocrystalline pure iron rods were fabricated by the equal channel angular pressure (ECAP) technique up to eight passes. The microstructure and grain size distribution, natural immersion and electrochemical corrosion in simulated body fluid, cellular responses and hemocompatibility were investigated in this study. The results indicate that nanocrystalline pure iron after severe plastic deformation (SPD) would sustain durable span duration and exhibit much stronger corrosion resistance than that of the microcrystalline pure iron. The interaction of different cell lines reveals that the nanocrystalline pure iron stimulates better proliferation of fibroblast cells and preferable promotion of endothelialization, while inhibits effectively the viability of vascular smooth muscle cells (VSMCs). The burst of red cells and adhesion of the platelets were also substantially suppressed on contact with the nanocrystalline pure iron in blood circulation. A clear size-dependent behavior from ...

2010-12-01

143

Formation of colloidal silver nanoparticles stabilized by Na+-poly(gamma-glutamic acid)-silver nitrate complex via chemical reduction process.

Magnetic particles have become very promising materials for drug delivery. However, preparation of magnetite particles with high surface area, biocompatibility, strong magnetic response, and suitable particle size still remains a major challenge. In this report, magnetite nanocrystal clusters with high surface areas were fabricated through a solvothermal process by introducing ammonium acetate as a porogen and trisodium citrate as a surface modification agent. The porosity, which was controlled by the reactant concentration, has been investigated in detail. The surface area of the nanocrystal clusters was as high as 141?m(2) g(-1) . Ibuprofen, as a model drug, was entrapped into the magnetite carriers. The interfacial interaction between the carboxylic groups on the drug molecules and the carboxylate groups on the carriers enhanced the loading efficiency. Low cytotoxicity in MCF-7 cell and in vitro constant drug release behavior combined with the high drug loading ...

2011-09-27

144

Evaluating the cytotoxicity of palladium/magnetite nano-catalysts intended for wastewater treatment

Macromolecular and polyanionic Na(+)-poly(gamma-glutamic acid) (PGA) silver nitrate complex acted as both a metal ion provider and a particle protector to fabricate nanosized silver colloids under chemical reduction by dextrose. The formation and size of particles have been characterized from transmission electron microscopy (TEM), dynamic light scattering analysis and UV-vis spectrophotometer. The results showed that the average particle size was 17.2+/-3.4 to 37.3+/-5.5 nm, apparently depending on the complex concentration. It was found that the rate constant and conversion of silver nanoparticles were proportional to the concentration of PGA. The growth mechanism of nanosized silver colloid was fully discussed. In addition, the in vitro cytotoxicity evaluated by L929 fibroblasts proliferation and antibacterial activity against Gram-positive strain (methicillin-resistant S. aureus (MRSA)) and Gram-negative strain (P. aeruginosa) bacteria have been assessed. ...

2007-05-18

145

Bip overexpression, but not CHOP inhibition, attenuates fatty-acid-induced endoplasmic reticulum stress and apoptosis in HepG2 liver cells

Palladium/magnetite nanoparticulate catalysts were developed for efficient elimination of halogenated organic pollutants from contaminated wastewater. Particle recovery from treated water can be ensured via magnetic separation. However, in worst-case scenarios, this catalyst removal step might fail, leading to particle release into the environment. Therefore, a toxicological study was conducted to investigate the impact of both pure magnetite and palladium/magnetite nanoparticle exposure upon human skin (HaCaT) and human colon (CaCo-2) cell lines and a cell line from rainbow trout gills (RTgill-W1). To quantify cell viability after particle exposure, three endpoints were examined for all tested cell lines. Additionally, the formation of reactive oxygen species was studied for the human cells. The results showed only minor effects of the particles on the tested cell systems and support the assumption that palladium/magnetite nano-catalysts can be implemented for a new wastewater ...

2010-01-01

146

British Library Electronic Table of Contents (United Kingdom)

Aims: In this study we investigated whether attenuation of endoplasmic reticulum stress (ER stress) could protect HepG2 cells from free fatty acid (FFA)-induced apoptosis. Main methods: Human liver cell line HepG2 cells were exposed to Sodium Palmitate (Pa) or Sodium Oleate (Ol). Apoptosis and ER stress of HepG2 cells were analyzed with flow cytometry, real-time RT-PCR and Western Blotting. An expression plasmid encoding for the ER chaperone immunoglobulin heavy chain-binding protein (Bip) was transfected into HepG2 cells to attenuate ER stress. Small interfering RNA siCHOP was used to knockdown the expression of C/EBP Homologous Protein (CHOP) in HepG2. Key findings: Pa led to cytotoxicity and apoptosis in HepG2 cells in a dose-dependent pattern and also induced ER stress indicated by inc...

2010-01-01

147

Antioxidant and toxicity tests of roasted noni (Morinda citrifolia) leaf infusion

British Library Electronic Table of Contents (United Kingdom)

Summary The antioxidant properties and toxicity profile of roasted noni (Morinda citrifolia L.) leaf infusion were evaluated. The 2,2-diphenylpicrylhydrazyl (DPPH) radical scavenging activity was greater than green tea infusion (81.6 +- 0.9% vs. 57.5 +- 1.8%, P < 0.001). The mean quercetin and kaempferol contents of roasted noni leaf infusion, as prepared by the consumer, were 0.24 +- 0.01 and 0.14 +- 0.01 mg mL-1, respectively. Tannic acid content was 10 +- 1 mg mL-1. The infusion was non-mutagenic in the reverse mutation test in Salmonella typhimurium and did not induce primary DNA damage in E. coli PQ37. Further, no significant primary DNA damage was induced by 5,15-dimethylmorindol, which was the only detectable anthraquinone in noni leaves. The infusion was not cytotoxic in the 24 h b...

2009-01-01

148

A new method for quantifiable and controlled dosage of particulate matter for in vitro studies: the electrostatic particulate dosage and exposure system (EPDExS).

A CD33-specific single-chain immunotoxin mediates potent apoptosis of cultured human myeloid leukaemia cells.

2008-06-08

149

Validation of immune function testing during a 4-week oral toxicity study with FK506.

A novel single-chain immunotoxin was constructed by combining a CD33-specific single chain Fv (scFv) antibody fragment with an engineered variant of Pseudomonas exotoxin A (ETA). The variant toxin carries the KDEL peptide at its C-terminus, a cellular peptide mediating improved retrograde transport to the endoplasmic reticulum. The purified recombinant fusion protein induced potent apoptosis of the human myeloid cell lines U937, HL-60 and THP-1. Up to 98% of U937 cells were eliminated after treatment for 72 h with a single dose of 500 ng/ml (c. 7 nmol/l). Killing was antigen-specific and occurred by apoptosis. A control protein, consisting of a CD19-specific scFv antibody fragment fused to the ETA-KDEL toxin, failed to induce death of the CD19-negative cell lines U937, HL-60 and THP-1. The CD33-ETA toxin also mediated apoptosis of fresh patient-derived acute myeloid leukaemia cells from bone marrow and peripheral blood. The pronounced antigen-restricted ...

2006-04-01

150

Photoaffinity labeling of ATP and NAD"+ binding sites on recombinant human interleukin 2

Assessment of the immune system's capability to respond to antigens with the generation of specific antibodies, whilst under the influence of a test article, is required in toxicity tests according to the European guideline for repeated dose toxicity testing of medicinal products. The purpose of this study in rats was to validate methodology for the determination of Keyhole Limpet Haemocyanin (KLH)-specific antibodies under the influence of an immunologically active compound. The immunosuppressant FK506, commercially available as Prograf, was administered orally (gavage) to five rats per sex per group at dosages of 0.5mg/kg per day or 3mg/kg per day, for a period of 4 weeks. On days 14 and 22, KLH was administered subcutaneously, with an adjuvant (AluGel), to the two treated groups and a control (i.e. without FK506 treatment) approximately 1h following administration of FK506. Terminal investigations included haematology parameters, titration of KLH-specific antibodies in serum ...

2004-04-01

151

Host resistance to rat cytomegalovirus (RCMV) and immune function in adult PVG rats fed herring from the contaminated Baltic Sea

Interleukin 2 (IL-2) is a T-cell-derived lymphokine critical in the activation and proliferation of T cells, B cells, and lymphokine-activated killer cells. It is a glycoprotein of #approx#15,500 daltons that is synthesized and secreted after activation by antigen or mitogen. By using the analogs 8-azidoadensoine 5'-[#gamma#-"3"2P]triphosphate ([#gamma#-"3"2P]8N_3ATP) and nicotinamide 2-azidoadenine [adenylate-"3"2P]dinucleotide ([#alpha#-"3"2P]2N_3NAD"+) as photoaffinity probes, the authors have detected specific, metal ion-requiring nucleotide binding sites on recombinant human IL-2 (rhIL-2). The specificity of these nucleotide interactions with rhIL-2 was demonstrated by saturation effects and by competition by the parent nucleotides at physiologically relevant concentrations. Saturation of photoinsertion into rhIL-2 occurred at 50 #mu#M [#gamma#-"3"2P]8N_3ATP. Saturation of photoinsertion with [#alpha#-"3"2P]2N_3NAD"+ was observed at 180 #mu#M. The extent of ...

152

The characteristics of a hydroxyapatite-chitosan-PMMA bone cement.

We carried out a feeding study in rats aimed at extending our aboservations of contaminant-induced immunosuppression in harbour seals. Two herring batches were freeze-dried, supplemented and fed to female adult PVG rats for a period of 4 1/2 months. Daily contaminant intakes of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalents (TEQ) were estimated to be 0.3 ng/kg body weight and 1.6 ng/kg in the Atlantic and Baltic groups, respectively. At the end of the feeding experiment, no contaminant-related changes in spleen CD{sub 4}{sup +}/CD{sub 8}{sup +} cellularity, natural killer cell activity, or mitogen-induced proliferative responses of thymus or spleen cells could be detected. However, total thymocyte numbers and thymus CD{sub 4}{sup +}/CD{sub 8}{sup +} ratios were reduced in the Baltic group. A novel model was established to assess the specific T-cell response to rat cytomegalovirus (RCMV). When applied to the feeding study, no differences between the ...

1996-08-01

153

Tests for the diagnosis of Clostridium difficile infection: the next generation.

In this study, we propose a new bioactive bone cement (BBC), composed of natural bone powder (hydroxyapatite; HA), chitosan powder, and the currently available polymethylmethacrylate (PMMA) bone cement, for use in orthopedic surgeries such as vertebroplasty or as bone filler. Three types of BBCs (BBC I, BBC II, and BBC III) were prepared with different composition ratios. In vitro tests and animal studies were performed with the new BBCs, and with a currently available commercial PMMA bone cement. Surface morphology, chemical composition, changes in pH over time, exothermic temperatures, intrusion, and cellular responses were investigated in vitro. Scanning electron microscopy (SEM) and radiological and histological examinations were performed in animal studies. The results showed that the major components of the BBCs were C, O, Ca, P, Cl, Si, S, Ba, and Mg. The pH values of the BBCs decreased after 1 day, but eventually recovered to 7.2-7.4. The water absorbency, weight loss, and ...

2004-11-01

154

Synthesis, characterization, and evaluation of a novel bifunctional chelating agent for the lead isotopes {sup 203}Pb and {sup 212}Pb

Clostridium difficile (C. difficile) causes 25-30% of cases of antibiotic associated diarrhea and most cases of pseudomembranous colitis. Patients presenting with diarrhea after hospitalization for 3 or more days should be tested for C. difficile. There are many options available for testing, each of which has inherent advantages and disadvantages. Most laboratories perform toxin testing using an enzyme immunoassay method. In general these tests have sensitivities ranging from 60 to 70% and specificities of 98%. When using these methods, symptomatic patients with negative tests should be tested by another more sensitive method. Until recently, cell culture cytotoxicity neutralization assays (CCNAs) were considered the gold standard in the U.S. A two-step algorithm using an EIA for glutamate dehydrogenase detection followed by testing positives using CCNA, offered an improved alternative until the availability of molecular assays. Although early studies that ...

2011-03-03

155

Synthesis, characterization, and evaluation of a novel bifunctional chelating agent for the lead isotopes "2"0"3Pb and "2"1"2Pb

Radioisotopes of Pb(II) have been of some interest in radioimmunotherapy and radioimmunoimaging (RII). However, the absence of a kinetically stable bifunctional chelating agent for Pb(II) has hampered its use for these applications. {sup 203}Pb (T{sub 1/2}=52.02 h) has application potential in RII, with a {gamma}-emission that is ideal for single photon emission computerized tomography, whereas {sup 212}Pb (T{sub 1/2}=10 h) is a source of highly cytotoxic {alpha}-particles via its decay to its {sup 212}Bi (T{sub 1/2}=60 min) daughter. The synthesis of the novel bifunctional chelating agent 2-(4-isothiocyanotobenzyl)-1,4,7,10-tetraaza-1,4,7,10-tetra-(2-carbamoyl methyl)-cyclododecane (4-NCS-Bz-TCMC) is reported herein. The Pb[TCMC]{sup 2+} complex was less labile to metal ion release than Pb[DOTA]{sup 2-} at pH 3.5 and below in isotopic exchange experiments. In addition to increased stability to Pb{sup 2+} ion release at low pH, the bifunctional TCMC ligand was ...

2000-01-01

156

Status of lead and bismuth for radioimmunoimaging and radioimmunotherapy

Radioisotopes of Pb(II) have been of some interest in radioimmunotherapy and radioimmunoimaging (RII). However, the absence of a kinetically stable bifunctional chelating agent for Pb(II) has hampered its use for these applications. "2"0"3Pb (T_1_/_2=52.02 h) has application potential in RII, with a #gamma#-emission that is ideal for single photon emission computerized tomography, whereas "2"1"2Pb (T_1_/_2=10 h) is a source of highly cytotoxic #alpha#-particles via its decay to its "2"1"2Bi (T_1_/_2=60 min) daughter. The synthesis of the novel bifunctional chelating agent 2-(4-isothiocyanotobenzyl)-1,4,7,10-tetraaza-1,4,7,10-tetra-(2-carbamoyl methyl)-cyclododecane (4-NCS-Bz-TCMC) is reported herein. The Pb[TCMC]"2"+ complex was less labile to metal ion release than Pb[DOTA]"2"- at pH 3.5 and below in isotopic exchange experiments. In addition to increased stability to Pb"2"+ ion release at low pH, the bifunctional TCMC ligand was found to have many other ...

2000-01-01

157

Relationship of DNA repair processes to mutagenesis and carcinogenesis in mammalian cells. Progress report, November 1, 1979-October 31, 1980

Tumor-targeted monoclonal antibodies (mAb) might be useful as diagnostic or therapeutic agents when linked to cytotoxic or imaging reagents. Our group is working to test this hypothesis by linking cytocidal and image-producing isotopes to mAb and testing the utility of the radioimmunoconjugates formed in animal model systems. Radioiodines were first employed for these purposes,but unfavorable nuclear properties (half-lives, #gamma#-ray and #beta#-particle energies) and chemical reactivity (deiodination in vivo) limit their utility. Labeling immunoproteins with metallic radionuclides offers more versatility in that the selection of potentially useful radiometals spans the periodic table.Of the metallic radionuclides with physical properties most suited for use with mAb in nuclear medicine, few are more available or desirable than those of bismuth ("2"1"2Bi) and lead ("2"0"3Pb, "2"1"2Pb), as listed in Table 1. "2"1"2Bi or "2"1"2Pb could serve as sources for highly ...

1990-08-26

158

Preparation of a high specific activity I-125 labeled styryl dye for leukocyte membrane labeling

The objective of this research is to determine the role of DNA repair in mutagenesis and carcinogenesis in mammalian cells. Use of the host-cell reactivation viral suicide enrichment procedure was initiated in the isolation of repair-deficient mutants. Lightly mutagenized BHK cells were infected with irradiated Herpes simplex virus (HSV); several radiation-sensitive strains were isolated among the survivors of the infection. The characterization of these strains is progressing and the enrichments are continuing. That alterations in the frequency of mutation of C3H/10T 1/2 cells, occurring as a result of holding the cells in a confluent state following treatment with ethylmethane sulfonate, parallel the alterations in the frequency of neoplastic transformation was found. The repair capabilities of BHK cells were found to be intermediate in comparison to repair-proficient and -deficient human cells with regard to the reactivation of HSV treated with various inactivating agents. The ...

159

Potent, selective and cell penetrant inhibitors of SF-1 by functional ultra-high-throughput screening.

The purpose of this work was to develop a high specific activity radioiodinated cell membrane probe for tracking lymphocytes in-vivo to replace the nucleus localizing, cytotoxic lipophilic chelates (In-111 oxine and Tc-99m HMPAO) currently used. Alkylation of parent dye 4-[2-[-N,N-didecylamino]phenyl]ethenyl pyridine with E-1-tributylstannyl-3-tosylpropene (prepared form E-1-tributylstannyl-1-propene-3-ol), gave a tributyltin precursor 1. Radiolabeled 3-[4-[2-[4-(N,N-didecylamino)phenyl]ethenyl]pyridino] E-[I-125]-1-iodopropene (2), was prepared from 1 using peracetic acid in acetonitrile/water. Labeling yields and specific activities achieved were 26% (#approx#2170 Ci/mmol), 40% (1220 Ci/mmol), and 55% (200 Ci/mmol) for nca, 0.4, and 2 nanomole carrier iodide runs respectively. Canine mixed leukocytes (0.5-1.0 x 10"8 cells) were labeled with 2 (67% and 42% yields for 200 Ci/mol and 1220 Ci/mmol preparations) and showed blood clearance similar to In 111 oxine. ...

1994-08-21

160

Pituitary gland height evaluated by MR in patients with {beta}-thalassemia major: a marker of pituitary gland function

The steroidogenic factor 1 (SF-1, also known as NR5A1) is a transcription factor belonging to the nuclear receptor superfamily. Whereas most of the members of this family have been extensively characterized, the therapeutic potential and pharmacology of SF-1 still remains elusive. Described here is the identification and characterization of selective inhibitory chemical probes of SF-1 by a rational ultra-high-throughput screening (uHTS) strategy. A set of 64,908 compounds from the National Institute of Health's Molecular Libraries Small Molecule Repository was screened in a transactivation cell-based assay employing a chimeric SF-1 construct. Two analogous isoquinolinones, ethyl 2-[2-[2-(2,3-dihydro-1,4-benzodioxin-7-ylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate (SID7969543) and ethyl 2-[2-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate and (SID7970631), were identified as potent submicromolar inhibitors, yielding IC(50) values of 760 and ...

2008-03-11

1 2 3 4 5 6 7 8 9

161

Optimizing the Protocol for Pulmonary Cryoablation: A Comparison of a Dual- and Triple-Freeze Protocol

In transfusion-dependent {beta}-thalassemia major, increased iron deposition in the pituitary gland has a cytotoxic effect leading mainly to hypogonadotropic hypogonadism. Our purpose was to assess in these patients the height of the pituitary gland and to evaluate whether it represents a marker of pituitary gland function. In 29 patients with {beta}-thalassemia major and 35 age- and gender-matched controls the pituitary gland height was evaluated in a midline sagittal scan using a spin echo T1-weighted (500/20 TR/TE) sequence. In all patients, an extensive endocrine evaluation was performed, including measurements of spontaneous and stimulated levels of gonadotropins, thyroid hormones, growth hormone, insulin-like growth factor, and adrenal hormones. The pituitary gland height was lower in thalassemic patients with hypogonadotropic hypogonadism (n=15) (mean 3.48; SD 0.46) than in the age- and gender-matched controls (mean 6.29; SD 0.77), (P<0.001). No ...

2001-12-01

162

Does tea tree oil have a place in the topical treatment of burns?

The purpose of this study was to compare a double freeze-thaw protocol to a triple freeze-thaw protocol for pulmonary cryoablation utilizing an in vivo porcine lung model. A total of 18 cryoablations were performed in normal porcine lung utilizing percutaneous technique with 9 each in a double- (10-5-10) and triple-freeze (3-3-7-7-5) protocol. Serial noncontrast CT images were obtained during the ablation. CT imaging findings and pathology were reviewed. No imaging changes were identified during the initial freeze cycle with either protocol. However, during the first thaw cycle, a region of ground glass opacity developed around the probe with both protocols. Because the initial freeze was shorter with the triple freeze-thaw protocol, the imaging findings were apparent sooner with this protocol (6 vs. 13 min). Also, despite a shorter total freeze time (15 vs. 20 min), the ablation zone identified with the triple freeze-thaw protocol was not significantly different from the double ...

2010-12-01

163

Antitumor activity of platinum(II) complexes with histamine and radioiodinated histamine in a transplantable murine adenocarcinoma model

Burnaid is a sorbalene-based cream containing 40 mg/g of tea tree oil and 1 mg/g of triclosan. This investigation was carried out to determine the effect of Burnaid, a commercial tea tree oil preparation, against Enterococcus faecalis (ATCC29212), Staphylococcus aureus (ATCC29213), Escherichia coli (ATCC25922), and Pseudomonas aeruginosa (ATCC27853), with the activity of the base product in the commercial preparation. The organisms were suspended in sterile saline (0.5 McFarland Standard) and inoculated onto horse blood agar (E. faecalis and S. aureus) or Mueller-Hinton agar (E. coli and P. aeruginosa). One hundred microliters of Burnaid unsterilized, Burnaid sterilized and the base product (Tinasolve) were placed in duplicate in wells cut into the agar plates. Sterility and inactivation cultures were also performed on the samples. None of the samples were found to be contaminated with bacteria prior to testing. Only S. aureus and E. coli showed zones of growth inhibition around the ...

1997-06-01

164