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1.
Opt Express ; 32(4): 5252-5260, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38439257

RESUMEN

Although Sc doped AlN (ScAlN) has been used extensively in micro-electro-mechanical systems (MEMS) devices and more recently in optical devices, there have not been thorough studies of its intrinsic optical losses. Here we explore the optical losses of the Sc0.30Al0.70N waveguide system by observing racetrack resonator waveguide quality factors. Using a partial physical etch, we fabricate waveguides and extract propagation losses as low as 1.6 ± 0.3 dB/cm at wavelengths around 1550 nm, mostly dominated by intrinsic material absorption from the Sc0.30Al0.70N thin film layer. The highest quality factor of the resonators was greater than 87,000. The propagation loss value is lower than any value previously published and shows that this material can be broadly used in optical modulators without significant loss.

2.
N Z Vet J ; 70(6): 340-348, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35968551

RESUMEN

CASE HISTORY: A 3-year-old, intact female mixed-breed dog, weighing 7 kg, was presented with generalised swelling of the tongue, leading to impaired deglutition and episodes of dyspnoea. From the age of 2 years, the dog had been under immunosuppressive therapy due to atopic dermatitis. CLINICAL FINDINGS AND TREATMENT: Multiple nodular lesions at the apex of the tongue were noted as well as mandibular and retropharyngeal lymph node enlargement. Serum biochemistry results showed inflammatory changes. The results of several biopsies taken over 7 months indicated persistent pyogranulomatous and necrotising glossitis despite ongoing antimicrobial treatment, first with amoxicillin/clavulanic acid and then pradofloxacin. No foreign material, acid-fast bacteria or fungal hyphae were detected throughout. The final diagnosis of Mycobacterium avium subsp. hominissuis (Mah) was reached after PCR and bacterial culture were carried out on the third biopsy sample. Therapy was initiated with rifampicin, clarithromycin and doxycycline, leading to complete remission of the lesions. DIAGNOSIS: Severe chronic pyogranulomatous and necrotising glossitis associated with infection by Mah. CLINICAL RELEVANCE: This report describes challenges in the diagnosis and therapy of a localised Mah infection in an iatrogenically immunocompromised dog. Successful treatment was only achieved with a specific combination of antibiotics administered long-term. ABBREVIATIONS: AF: Acid-fast; ALP: Alkaline phosphatase; CT: Computed tomography; MAC: Mycobacterium avium complex; Mah: Mycobacterium avium subsp. hominissuis.


Asunto(s)
Enfermedades de los Perros , Glositis , Fosfatasa Alcalina , Amoxicilina , Animales , Antibacterianos , Claritromicina , Ácido Clavulánico , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Doxiciclina , Femenino , Glositis/diagnóstico , Glositis/tratamiento farmacológico , Glositis/veterinaria , Inmunomodulación , Mycobacterium , Mycobacterium avium , Rifampin
3.
Nanotechnology ; 31(44): 445204, 2020 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-32647099

RESUMEN

Despite being known of for decades, the actual realization of memory devices based on the memristive effect is progressing slowly, due to processing requirements and the need for exotic materials which are not compatible with today's complementary-metal-oxide-semiconductor (CMOS) technology. Here, we report an experimental study on a Ge quantum wire device featuring distinct signatures of memristive behavior favorable for integration in CMOS platform technology. Embedding the quasi-1D Ge quantum wire into an electrostatically modulated back-gated field-effect transistor, we demonstrate that individual current transport channels can be addressed directly by controlling the surface trap assisted electrostatic gating. The resulting quantization of the current represents the ultimate limit of memristors with practically zero off-state current and low footprint. In addition, the proposed device has the advantage of non-destructive successive reading cycles capability. Importantly, our findings provide a framework towards fully CMOS compatible ultra-scaled Ge based memristors.

4.
Int J Med Microbiol ; 308(7): 899-911, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29937390

RESUMEN

In 2011, Germany was struck by the largest outbreak of hemolytic uremic syndrome. The highly virulent E. coli O104:H4 outbreak strain LB226692 possesses a blended virulence profile combining genetic patterns of human adapted enteroaggregative E. coli (EAEC), rarely detected in animal hosts before, and enterohemorrhagic E. coli (EHEC), a subpopulation of Shiga toxin (Stx)-producing E. coli (STEC) basically adapted to the ruminant host. This study aimed at appraising the relative level of adaptation of the EAEC/EHEC hybrid strain LB226692 to humans and cattle. Adherence and invasion of the hybrid strain to intestinal (jejunal and colonic) epithelial cells (IEC) of human and bovine origin was compared to that of E. coli strains representative of different pathovars and commensal E. coli by means of light and electron microscopy and culture. Strain-specific host gene transcription profiles of selected cytokines and chemokines as well as host-induced transcription of bacterial virulence genes were assessed. The release of Stx upon host cell contact was quantified. The outbreak strain's immunomodulation was assessed by cultivating primary bovine macrophages with conditioned supernatants from IEC infection studies with E. coli, serving as model for the innate immunity of the bovine gut. The outbreak strain adhered to IEC of both, human and bovine origin. Electron microscopy of infected cells revealed the strain's particular affinity to human small IEC, in contrast to few interactions with bovine small IEC. The outbreak strain possessed a high-level of adhesive power, similar to human-associated E. coli strains and in contrast to bovine-associated STEC strains. The outbreak strain displayed a non-invasive phenotype, in contrast to some bovine-associated E. coli strains, which were invasive. The outbreak strain provoked some pro-inflammatory activity in human cells, but to a lower extent as compared to other pathotypes. In contrasts to bovine-associated E. coli strains, the outbreak strain induced marked pro-inflammatory activity when interacting with bovine host cells directly (IEC) and indirectly (macrophages). Among stx2-positive strains, the human-pathogenic strains (LB226692 and EHEC strain 86-24) released higher amounts of Stx compared to bovine-associated STEC. The findings imply that the outbreak strain is rather adapted to humans than to cattle. However, the outbreak strain's potential to colonize IEC of both host species and the rather mixed reaction patterns observed for all strains under study indicate, that even STEC strains with an unusual genotype as the EHEC O104:H4 outbreak strain, i.e. with an EAEC genetic background, may be able to conquer other reservoir hosts.


Asunto(s)
Infecciones por Escherichia coli/epidemiología , Escherichia coli O104/patogenicidad , Síndrome Hemolítico-Urémico/epidemiología , Inflamación/inmunología , Mucosa Intestinal/microbiología , Animales , Bovinos , Línea Celular , Chlorocebus aethiops , Colon/citología , Colon/microbiología , Brotes de Enfermedades , Células Epiteliales/microbiología , Infecciones por Escherichia coli/microbiología , Escherichia coli O104/inmunología , Escherichia coli O104/aislamiento & purificación , Alemania/epidemiología , Síndrome Hemolítico-Urémico/microbiología , Interacciones Huésped-Patógeno/fisiología , Humanos , Mucosa Intestinal/citología , Yeyuno/citología , Yeyuno/microbiología , Macrófagos/microbiología , Toxina Shiga/biosíntesis , Células Vero , Virulencia
5.
Nanotechnology ; 26(47): 475701, 2015 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-26535785

RESUMEN

Recently, focused electron beam-induced deposition has been employed to prepare functional magnetic nanostructures with potential in nanomagnetic logic and sensing applications by using homonuclear precursor gases like Fe(CO)5 or Co2(CO)8. Here we show that an extension towards the fabrication of bi-metallic compounds is possible by using a single-source heteronuclear precursor gas. We have grown CoFe alloy magnetic nanostructures from the HFeCo3(CO)12 metal carbonyl precursor. The compositional analysis indicates that the samples contain about 80 at% of metal and 10 at% of carbon and oxygen. Four-probe magnetotransport measurements are carried out on nanowires of various sizes down to a width of 50 nm, for which a room temperature resistivity of 43 µΩcm is found. Micro-Hall magnetometry reveals that 50 nm × 250 nm nanobars of the material are ferromagnetic up to the highest measured temperature of 250 K. Finally, the transmission electron microscopy (TEM) microstructural investigation shows that the deposits consist of a bcc Co-Fe phase mixed with a FeCo2 O4 spinel oxide phase with nanograins of about 5 nm diameter.

6.
Br J Cancer ; 109(6): 1570-8, 2013 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-23942071

RESUMEN

BACKGROUND: Antibody drug conjugates (ADCs) and immunotoxins (ITs) are promising anticancer immunotherapeutics. Despite their encouraging performance in clinical trials, both ADCs and ITs often suffer from disadvantages such as stoichiometrically undefined chemical linkage of the cytotoxic payload (ADCs) and the potential immunogenicity of toxins derived from bacteria and plants (ITs). METHODS: Human microtubule-associated protein tau (MAP) was cloned in-frame with human EGF, expressed in E. coli and purified by standard chromatographic methods. The in vitro activity was confirmed by flow cytometry, cell viability assays and tubulin polymerisation assay. The in vivo efficacy was demonstrated using noninvasive far-red in vivo imaging. RESULTS: The EGF-MAP selectively induced apoptosis in EGFR-overexpressing proliferating cancer cells through stabilisation of microtubules. Nonproliferating cells were not affected, demonstrating superior selectivity of EGF-MAP for cancer cells. The EGF-MAP was well tolerated at high doses in mice compared with the ETA'-based control. The in vivo efficacy of EGF-MAP was demonstrated in a tumour xenograft mouse model. CONCLUSION: Our data indicate the general mechanism of action for a new class of human immunotherapeutic reagents suitable for the treatment of cancer. This approach combines the binding specificity of targeting ligands with the selective cytotoxicity of MAP towards proliferating cells.


Asunto(s)
Factor de Crecimiento Epidérmico/farmacología , Proteínas Recombinantes de Fusión/farmacología , Proteínas tau/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Factor de Crecimiento Epidérmico/biosíntesis , Factor de Crecimiento Epidérmico/química , Factor de Crecimiento Epidérmico/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Distribución Aleatoria , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Transfección , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas tau/biosíntesis , Proteínas tau/química , Proteínas tau/genética
7.
Hautarzt ; 64(4): 283-9, 2013 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-23532505

RESUMEN

BACKGROUND: The prevalence of onychomycosis is rising worldwide. Before starting antifungal treatment, an exact mycological diagnosis should be obtained. The current laboratory diagnosis of dermatomycoses is based on the detection of the causative agent by microscopy and culture. These conventional diagnostic methods for fungal infections often are not the best solution because they are time-consuming, cultures are false-negative and direct examination identifies non-vital structures which cannot be used for speciation. PATIENTS AND METHODS: A total of 218 patients presenting in a surgical practice over 3 months with clinical signs of tinea pedis and/or onychomycosis were involved in the prospective study. All patients had predisposing factors for tinea pedis and tinea unguium, such as vascular insufficiency, diabetes mellitus, and leg ulcers. Nail specimens and skin scrapings were investigated for fungi using Blancophor® preparation, and cultured. In addition to conventional diagnostics, PCR (polymerase chain reaction) for detection of dermatophyte DNA was employed. This PCR-Elisa assay is based on the use of specific primers which target the topoisomerase II gene. This allows the highly specific molecular identification of Trichophyton (T.) rubrum, T. interdigitale, and Epidermophyton floccosum directly in clinical samples. RESULTS: 23.9 % of patients were culture-positive for dermatophytes (either T. rubrum, or T. interdigitale). With PCR, dermatophyte DNA either of T. rubrum or T. interdigitale could be detected in nail samples and skin scrapings from at least 29.9 % of all patients. Epidermophyton floccosum was not found in this study, neither by cultivation nor by PCR. The diagnostic sensitivity of the PCR-Elisa assay was calculated as 79.0% ; the diagnostic specificity as 85.5 %. CONCLUSION: PCR-Elisa evaluation makes possible a rapid, specific and sensitive diagnosis of dermatophytosis of the nails and skin within 24 (maximal 48) hours with identification of the involved species.


Asunto(s)
Arthrodermataceae/clasificación , Arthrodermataceae/genética , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Tipificación Micológica/métodos , Onicomicosis/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Tiña del Pie/diagnóstico , Anciano , Arthrodermataceae/aislamiento & purificación , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Onicomicosis/microbiología , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tiña del Pie/microbiología
8.
J Cyst Fibros ; 22(5): 941-943, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37045685

RESUMEN

We present the case of a girl (now 11 years and 9 months old) with cystic fibrosis (F508del homozygote), who developed pruritic rash and urticaria six days after the first dose of the CFTR modulators lumacaftor/ivacaftor. The treatment was paused and had to be interrupted due to an immediate recurrence of the urticarial rash after rechallenge. We developed a drug desensitization protocol, aligned to protocols used for desensitization against oral antibiotics. In contrast to other published protocols, it was performed by rapidly increasing the dose of lumacaftor/ivacaftor granulate at 15 min intervals. The medication was continued without interruption, the rash did not reappear during follow-up of two years. This drug desensitization protocol provides a potential new therapeutic option for patients with drug hypersensitivity reactions to CFTR modulators, especially when there are no alternative treatments. Lumacaftor/ivacaftor is available as granulate, doses can be titrated during desensitization and used for long-term treatment.


Asunto(s)
Fibrosis Quística , Exantema , Femenino , Humanos , Lactante , Fibrosis Quística/diagnóstico , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/uso terapéutico , Volumen Espiratorio Forzado , Combinación de Medicamentos , Aminofenoles/uso terapéutico , Aminopiridinas/uso terapéutico , Benzodioxoles/uso terapéutico , Tolerancia a Medicamentos , Exantema/inducido químicamente , Exantema/tratamiento farmacológico , Mutación
9.
Immunother Adv ; 3(1): ltac023, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36789295

RESUMEN

Introduction: Current treatments for asthma help to alleviate clinical symptoms but do not cure the disease. In this study, we explored a novel therapeutic approach for the treatment of house dust mite allergen Der p 1induced asthma by aiming to eliminate specific population of B-cells involved in memory IgE response to Der p 1. Materials and Methods: To achieve this aim, we developed and evaluated two different proDer p 1-based fusion proteins; an allergen-toxin (proDer p 1-ETA) and an allergen-drug conjugate (ADC) (proDer p 1-SNAP-AURIF) against Der p 1 reactive hybridomas as an in vitro model for Der p 1 reactive human B-cells. The strategy involved the use of proDer p 1 allergen as a cell-specific ligand to selectively deliver the bacterial protein toxin Pseudomonas exotoxin A (ETA) or the synthetic small molecule toxin Auristatin F (AURIF) into the cytosol of Der p 1 reactive cells for highly efficient cell killing. Results: As such, we demonstrated recombinant proDer p 1 fusion proteins were selectively bound by Der p 1 reactive hybridomas as well as primary IgG1+ B-cells from HDM-sensitized mice. The therapeutic potential of proDer p 1-ETA' and proDer p 1-SNAP-AURIF was confirmed by their selective cytotoxic activities on Der p 1 reactive hybridoma cells. The allergen-toxin demonstrated superior cytotoxic activity, with IC50 values in the single digit nanomolar value, compared to the ADC. Discussions: Altogether, the proof-of-concept experiments in this study provide a promising approach for the treatment of patients with house dust mite-driven allergic asthma.

10.
World J Urol ; 29(6): 779-86, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20640575

RESUMEN

PURPOSE: Renal cell carcinoma (RCC) is highly resistant to chemotherapy and unresponsive to radio- and immunotherapy. Recently, we have documented that the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) in combination with low-dosed interferon (IFN)-alpha significantly inhibits RCC proliferation and adhesion in vitro and in vivo. The current study investigated the effects of these compounds on gene transcription of metastatic RCC cell line Caki-1 after 3 and 5 days exposure. METHODS: To evaluate the gene expression profiles of the RCC cells, we performed microarray analysis using Affymetrix GeneChip. Selected significant genes were further validated by Real Time PCR. RESULTS: Microarray revealed that VPA altered genes that are involved in cell growth, cell survival, immune response, cell motility and cell adhesion. Combination of VPA with IFN-alpha not only enhanced the effects on gene transcription but also resulted in the expression of novel genes, which were not induced by either VPA or IFN-alpha alone. Among the up-regulated genes were chemokines (CXCL10, CXCL11, CXCL16) and integrins (ITGA2, ITGA4, ITGA5, ITGA6, ITGA7). Genes encoding for adhesion molecules (NCAM1, ICAM1, VCAM1) were also modulated. Real Time PCR approved these findings. CONCLUSION: This data provides insight into the molecular mechanism of action of the combined treatment of VPA and IFN-alpha in RCC. Implications are that the combined application of VPA and IFN-alpha may represent a more efficient alternative to existing therapy options for RCC.


Asunto(s)
Carcinoma de Células Renales/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Interferón-alfa/farmacología , Neoplasias Renales/genética , Ácido Valproico/farmacología , Carcinoma de Células Renales/patología , Adhesión Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Factores Inmunológicos/farmacología , Neoplasias Renales/patología , Análisis por Micromatrices
11.
Poult Sci ; 90(10): 2275-80, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21934010

RESUMEN

The use of protective, probiotic cultures in poultry farming may serve as a useful strategy to improve food product safety from the beginning of the food chain and thus to protect consumer health. The objective of this study was to investigate the effect of the probiotic strain Bifidobacterium longum PCB133 on innate and adaptive immune responses in turkeys beginning at 2 wk of age, under farming conditions. The vaccination efficiency against Newcastle disease virus served as the primary endpoint. At 2 wk of age, male turkeys (British United Turkey Big 6 strain) were randomly assigned to the control (n = 25) or probiotic group (n = 25). Turkeys in the probiotic group received the probiotic B. longum PCB133 (at least 3 × 10(7) cfu/d) incorporated into the daily feed ration for 5 wk, until slaughter at 7 wk of age. At the beginning of the probiotic intervention, birds in both groups were vaccinated against Newcastle disease. Birds were weighed weekly throughout the intervention period, and finally blood sera and heparinized blood were collected for immune function tests (lymphocyte proliferation, phagocytosis, respiratory burst), and for the determination of Newcastle disease virus antibody titers. No effects on BW gain and on the proliferation of blood lymphocytes were elicited by the 5-wk intervention with the probiotic. Concerning the primary endpoint of the study (i.e., specific antibody production as a response to vaccination against Newcastle disease), no adjuvant effect of the probiotic could be determined. In addition, innate immune functions tested were not significantly affected. In conclusion, first scientific evidence on the application of the probiotic strain B. longum PCB133 in turkeys beginning at 2 wk of age does not support an improvement in live performance, humoral immunity, or innate immunity.


Asunto(s)
Inmunidad Adaptativa , Bifidobacterium , Inmunidad Innata , Probióticos/administración & dosificación , Pavos/inmunología , Animales , Dieta , Activación de Linfocitos/inmunología , Masculino , Enfermedad de Newcastle/inmunología , Enfermedad de Newcastle/prevención & control , Virus de la Enfermedad de Newcastle/inmunología , Vacunación/veterinaria
12.
Gene Ther ; 17(2): 181-9, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19741732

RESUMEN

Transplantation of pigment epithelial cells in patients with age-related macular degeneration and Parkinson's disease has the potential to improve functional rehabilitation. Genetic modification of cells before transplantation may allow the delivery of neuroprotective factors to achieve functional improvement. As transplantation of cells modified using viral vectors is complicated by the possible dissemination of viral particles and severe immune reactions, we have explored non-viral methods to insert genetic material in pigment epithelial cells. Using lipofection or nucleofection ARPE-19 cells, freshly isolated and primary retinal and iris pigment epithelial (IPE) cells were transfected with plasmids encoding green fluorescent protein (GFP) and with three plasmids encoding recombinant pigment epithelium-derived factor (PEDF) and GFP. Transfection efficiency was evaluated by fluorescence microscopy and stability of protein expression by immunoblotting. Pigment epithelial cells were successfully transfected with plasmid encoding GFP. Expression of GFP in ARPE-19 was transient, but was observed for up to 1 year in IPE cells. Analysis of pigment epithelial cells transfected with PEDF plasmids revealed that PEDF fusion proteins were successfully expressed and functionally active. In conclusion, efficient transfer of genetic information in pigment epithelial cells can be achieved using non-viral transfection protocols.


Asunto(s)
Proteínas del Ojo/genética , Proteínas Fluorescentes Verdes/genética , Iris/metabolismo , Factores de Crecimiento Nervioso/genética , Epitelio Pigmentado Ocular/metabolismo , Plásmidos , Serpinas/genética , Transfección/métodos , Animales , Células Cultivadas , Electroporación , Humanos , Ratas , Porcinos
13.
Br J Dermatol ; 163(2): 279-86, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20426788

RESUMEN

BACKGROUND: Dysregulated, activated macrophages play a pivotal role in chronic inflammatory diseases such as arthritis and atopic dermatitis. These cells display increased expression of the high-affinity Fcgamma receptor (CD64), making them ideal targets for CD64-specific immunotoxins. We previously showed that a chemically linked immunotoxin, the monoclonal H22-RicinA, specifically eliminated infiltrating activated macrophages and resolved chronic cutaneous inflammation. However, several disadvantages are associated with classic immunotoxins, and we therefore followed a fusion protein strategy to express the antigen-binding site alone (scFv H22) fused to a derivative of Pseudomonas exotoxin A (ETA'). OBJECTIVES: To assess the potential effect of increased valency on efficacy, we produced monovalent [H22(scFv)-ETA'] and bivalent [H22(scFv)(2)-ETA'] versions and evaluated their potential for eliminating activated macrophages both in vitro and in vivo. METHODS: Both immunotoxins were produced by bacterial fermentation. Binding was assessed by flow cytometry on the monocytic CD64+ cell line U937. Toxicity was analysed by XTT and apoptosis induction by annexin V bioassay. The in vivo effect was tested in a human CD64 transgenic mouse model for cutaneous inflammation. RESULTS: The cytotoxic effects of both immunotoxins were clearly due to apoptosis with an IC(50) of 140 pmol L(-1) for monovalent and only 14 pmol L(-1) for the divalent version. In vivo treatment with H22(scFv)-ETA' reduced CD64+ activated macrophages to 21% of their initial numbers whereas H22(scFv)(2)-ETA' treatment reduced these cells to 4.8% (P < 0.001). CONCLUSIONS: These data clearly show increased efficacy due to increased valency of the anti-CD64 immunotoxin. Both recombinant immunotoxins have a low IC(50), making them suitable for the treatment of diseases involving dysregulated, activated macrophages.


Asunto(s)
Exotoxinas/farmacología , Inmunotoxinas/farmacología , Inflamación/fisiopatología , Macrófagos/inmunología , Receptores de IgG/inmunología , Enfermedades de la Piel/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Enfermedad Crónica , Modelos Animales de Enfermedad , Exotoxinas/inmunología , Humanos , Fragmentos de Inmunoglobulinas/inmunología , Fragmentos de Inmunoglobulinas/farmacología , Inmunotoxinas/química , Inmunotoxinas/inmunología , Macrófagos/efectos de los fármacos , Ratones , Ratones Transgénicos , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/farmacología , Enfermedades de la Piel/inmunología
15.
J Biomed Biotechnol ; 2010: 187621, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20204062

RESUMEN

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) gamma-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA). While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms.


Asunto(s)
ADP Ribosa Transferasas/administración & dosificación , Autoanticuerpos/inmunología , Toxinas Bacterianas/administración & dosificación , Exotoxinas/administración & dosificación , Inmunotoxinas/administración & dosificación , Receptores Nicotínicos/inmunología , Proteínas Recombinantes de Fusión/administración & dosificación , Rabdomiosarcoma/tratamiento farmacológico , Anticuerpos de Cadena Única/inmunología , Factores de Virulencia/administración & dosificación , ADP Ribosa Transferasas/genética , Animales , Autoanticuerpos/administración & dosificación , Autoanticuerpos/genética , Toxinas Bacterianas/genética , Procesos de Crecimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Exotoxinas/genética , Femenino , Citometría de Flujo , Humanos , Inmunotoxinas/genética , Inmunotoxinas/inmunología , Ratones , Ratones SCID , Receptores Nicotínicos/administración & dosificación , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Rabdomiosarcoma/inmunología , Rabdomiosarcoma/patología , Anticuerpos de Cadena Única/administración & dosificación , Anticuerpos de Cadena Única/genética , Factores de Virulencia/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Exotoxina A de Pseudomonas aeruginosa
16.
Pathologe ; 31 Suppl 2: 215-20, 2010 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-20730458

RESUMEN

AIMS: To improve survival of patients with advanced rhabdomyosarcomas (RMS), we aimed to adoptively transfer T-cells with redirected specificity for the fetal acetylcholine receptor (AChR), an RMS-specific cell surface antigen. METHODS: A "second generation" chimeric antigen receptor (CAR) with a combined CD28-CD3ζ signaling domain was derived from our previously described chimeric antigen receptor composed of an extracellular human anti-fAChR antibody fragment, an Fc hinge region, and the intracellular T-cell receptor zeta chain. Lymphocytes from the peripheral blood were modified by retroviral transduction and monitored by FACS analysis. Cytotoxicity of modified T-cells towards RMS cells was recorded by MTT-based viability tests; expression of co-stimulatory molecules and anti-apoptotic genes was studied by FACS and qRT-PCR analysis. RESULTS: Co-stimulatory molecules were expressed in low levels on RMS cells giving the rationale to generate a CD28-CD3ζ signalling CAR (chimeric antigen receptor) for redirecting T-cells. T-cells were successfully engineered with the "second generation" AChR-specific chimeric antigen receptor. Despite of high CAR expression engineered T-cells showed low killing efficiency towards RMS compared to redirected killing of CD20+ lymphoma or CEA-expressing adenocarcinoma cell lines when redirected by CD20- and/or CEA-specific CAR. CONCLUSIONS: Data suggest that RMS cells exhibit resistance to a T-cell attack redirected by a fAChR-specific CAR. Inhibition of anti-apoptotic pathways in those cells may improve sensitivity to conventional as well as T-cell-based therapeutics.


Asunto(s)
Inmunoterapia Adoptiva/métodos , Rabdomiosarcoma/terapia , Linfocitos T/inmunología , Línea Celular Tumoral , Quimerismo , Pruebas Inmunológicas de Citotoxicidad , Humanos , Fragmentos Fc de Inmunoglobulinas/inmunología , Fragmentos de Inmunoglobulinas/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Receptores Colinérgicos/inmunología , Rabdomiosarcoma/inmunología , Rabdomiosarcoma/patología
17.
Med Eng Phys ; 81: 125-129, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32473841

RESUMEN

Physical activity (PA) is highly recommended in the management of most chronic diseases. For these patients, the smart electric bicycle can be effective to improve adherence to this behavior. The E-bike used in this study (called VELIS) has an innovative onboard technology that allows for subject monitoring and the engine power is designed to adapt to the user's abilities. A prerequisite for the use of the VELIS with patients is to initially carry out a pilot study on healthy subjects. The objective was to evaluate the impact of the customizable settings on physiological parameters and to ensure this prototype's efficiency and safety of use. Twelve healthy participants with various profiles (physical condition, used to cycling or not) were included. They have completed four times a 14 km itinerary with various settings of the VELIS. We recorded GPS data, heart rate and perceived exertion. Based on exercise intensity, we confirm that riding an E-bike should be considered as a physical activity. Safety of the participants is ensured by the engine brake. Recordings show that it took between 1 and 3 min for the novice to become familiar with the VELIS and to get optimal assistance. The main finding of this pilot study confirms that VELIS is an easy to use and secure tool to make PA approachable, whatever the level of training in healthy subjects.


Asunto(s)
Ciclismo , Electricidad , Electrónica , Ejercicio Físico , Adulto , Anciano , Ciclismo/educación , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto
18.
J Appl Microbiol ; 107(5): 1697-710, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19457029

RESUMEN

AIMS: This study was prompted to investigate the intestinal localization and colonization of orally administered Escherichia coli Nissle 1917 (EcN) in piglets. METHODS AND RESULTS: EcN was fed to ten EcN-negative piglets (3 months) over seven consecutive days. Faecal samples were collected repeatedly and tested for EcN-DNA by a combined culture/PCR assay and for viable EcN by culture methods, respectively. EcN-DNA was detectable in faeces of all piglets within the first 24 h after it was added to the feed. After the administration of EcN had been stopped, the presence of EcN-DNA in faecal samples indicated that all piglets shedded EcN with their faeces intermittently through up to 33 days. In addition, E. coli strains indistinguishable from EcN by all markers tested (rdar colony morphotype, multiplex PCR and GEI II-PCR analyses, XbaI-pattern, K5 phage susceptibility) were isolated from faecal samples and from mucosal swabs taken at euthanasia at the end of the experiment. CONCLUSIONS: EcN colonizes the intestine and persists in conventionally reared piglets for at least 4 weeks upon oral administration. SIGNIFICANCE AND IMPACT OF THE STUDY: Results of this study have implications for efficacy and safety assessments of EcN as a probiotic strain for use in pigs.


Asunto(s)
Escherichia coli/aislamiento & purificación , Intestinos/microbiología , Probióticos/análisis , Porcinos/microbiología , Administración Oral , Animales , ADN Bacteriano/análisis , Escherichia coli/genética , Heces/microbiología , Límite de Detección , Reacción en Cadena de la Polimerasa/métodos , Sensibilidad y Especificidad
19.
J Comp Pathol ; 172: 1-4, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31690406

RESUMEN

Mycobacterium bovis is the main agent of bovine tuberculosis, but has also zoonotic potential. An 8-month-old female domestic shorthaired cat imported from Ukraine developed wound complications after abdominal surgery. A second surgery performed in Germany showed a focal, partly cystic mass within the mesentery. Despite antimicrobial treatment, the cat did not recover and was humanely destroyed. Grossly, several abdominal lymph nodes were enlarged. Histopathology revealed a mild to moderate, multifocal, granulomatous to pyogranulomatous, partially necrotizing inflammation, most prominent in the abdominal cavity. Within the lesions there were acid-fast bacilli within the cytoplasm of macrophages demonstrated by Ziehl-Neelsen staining. Further investigations revealed M. bovis SB0950 in the affected tissues.


Asunto(s)
Mycobacterium bovis/aislamiento & purificación , Herida Quirúrgica/microbiología , Tuberculosis Bovina/microbiología , Animales , Enfermedades de los Gatos/microbiología , Gatos , Bovinos , Femenino , Ganglios Linfáticos/microbiología , Ganglios Linfáticos/patología , Macrófagos/microbiología , Macrófagos/patología , Herida Quirúrgica/complicaciones , Zoonosis/microbiología
20.
BMC Res Notes ; 12(1): 311, 2019 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-31151479

RESUMEN

OBJECTIVES: The objective of this study was to establish transcriptome assemblies of Festulolium hybrids under salt stress, and identify genes regulated across the hybrids in response to salt stress. The development of transcriptome assemblies for Festulolium hybrids and cataloguing of genes regulated under salt stress will facilitate further downstream studies. RESULTS: Plants were grown at three salt concentrations (0.5%, 1% and 1.5%) and phenotypic and transcriptomic data was collected. Salt stress was confirmed by progressive loss of green leaves as salt concentration increased from 0 to 1.5%. We generated de-novo transcriptome assemblies for two Festulolium pabulare festucoid genotypes, for a single Festulolium braunii genotype, and a single F. pabulare loloid genotype. We also identified 1555 transcripts that were up regulated and 1264 transcripts that were down regulated in response to salt stress in the Festulolium hybrids. Some of the identified transcripts showed significant sequence similarity with genes known to be regulated during salt and other abiotic stresses.


Asunto(s)
Festuca/genética , Regulación de la Expresión Génica de las Plantas , Hibridación Genética/genética , Lolium/genética , Estrés Salino/genética , Transcriptoma , Festuca/crecimiento & desarrollo , Perfilación de la Expresión Génica , Genes de Plantas/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Lolium/crecimiento & desarrollo , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Transcripción Genética
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