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OBJECTIVES: Epigenetically modified fibroblasts contribute to chronicity in inflammatory diseases. Reasons for the relapsing character of large vessel vasculitis (LVV) remain obscure, including the role of fibroblasts, in part due to limited access to biopsies of involved tissue.68Ga FAPI-46 (FAPI)-PET/CT detects activated fibroblasts in vivo. In this exploratory pilot study, we tested the detection of fibroblast activation in vessel walls using FAPI-PET/CT in LVV with aortitis. METHODS: 8 LVV patients with aortitis and 8 age- and gender-matched controls were included. Distribution of FAPI uptake was evaluated in the aorta and large vessels. FAPI-uptake was compared with MRI inflammatory activity scores. Imaging results were compared with clinical parameters such as serum inflammatory markers, time of remission and medication. RESULTS: Three aortitis patients were clinically active, five in remission. Irrespective of activity, FAPI uptake was significantly enhanced in aortitis compared with controls. Patients in remission had a mean duration of remission of 2.8 years (range 1-4 years), yet significant FAPI uptake in the vessel wall was found.In remitted aortitis, MRI inflammatory scores were close to be negative, while in 4/5 patients visually identifiable FAPI uptake was observed. CONCLUSIONS: This pilot feasibility study shows significant tracer uptake in the aortic walls in LVV. FAPI positivity indicates ongoing fibroblast pathology in clinically remitted LVV.
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BACKGROUND: Contrast generation by chemical exchange saturation transfer (CEST) is a recently emerging magnetic resonance imaging (MRI) research field with high clinical potential. METHODS: This review covers the methodological principles and summarizes the clinical experience of CEST imaging studies in diagnostic oncology performed to date. RESULTS AND CONCLUSION: CEST enables the detection of lowly concentrated metabolites, such as peptides and glucose, through selective saturation of metabolite-bound protons and subsequent magnetization transfer to free water. This technology yields additional information about metabolic activity and the tissue microenvironment without the need for conventional contrast agents or radioactive tracers. Various studies, mainly conducted in patients with neuro-oncolgic diseases, suggest that this technology may aid to assess tumor malignancy as well as therapeutic response prior to and in the first follow-up after intervention. KEY POINTS: CEST-MRI enables the indirect detection of metabolites without radioactive tracers or contrast agents. Clinical experience exists especially in the setting of neuro-oncologic imaging. In oncologic imaging, CEST-MRI may improve assessment of prognosis and therapy response.
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Imagen por Resonancia Magnética , Neoplasias , Protones , Humanos , Neoplasias/diagnóstico por imagenRESUMEN
BACKGROUND: Paediatric onset multiple sclerosis (POMS) is associated with reduced brain and deep grey matter volume in comparison with that in healthy controls and individuals with adult onset multiple sclerosis (AOMS). The aim of our study was to evaluate the impact of POMS on adult brain volume with adjustment for other parameters, such as disease duration. PATIENTS AND METHODS: We recruited 20 POMS and 40 AOMS patients and 20 healthy controls matched for age and sex. All study participants were adults at the time of inclusion in the study. All study subjects underwent brain magnetic resonance imaging (MRI) to evaluate whole brain, white matter, grey matter, cortical, and deep grey matter volumes. Clinical features, such as the Expanded Disability Status Scale (EDSS) score and disease duration, were also assessed. RESULTS: Brain (pâ¯=â¯0.01), grey matter (pâ¯=â¯0.01), and deep grey matter volume (pâ¯=â¯0.03) was significantly lower in POMS patients than in AOMS patients, while no differences were detected in the volume of white matter or cortical grey matter. A multiple linear regression analysis showed a relationship between brain volume (dependent variable) and the independent variables age (pâ¯<â¯0.000) and paediatric onset (pâ¯<â¯0.001), while other independent variables, including disease duration, sex, and disability, were not significantly different among groups. There were significant differences in thalamic volume among POMS and AOMS patients and healthy controls. CONCLUSION: Our data support the previous findings that POMS patients have reduced brain and deep grey matter volume, particularly thalamic volume, compared with sex- and age-matched AOMS patients and healthy controls. These findings appear to be independent of disease duration and other clinical features.
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Encéfalo/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico por imagen , Adulto , Edad de Inicio , Encéfalo/patología , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Lateralidad Funcional , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/patología , Análisis Multivariante , Tamaño de los Órganos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Adulto JovenRESUMEN
BACKGROUND: Oligoclonal bands of IgG (OB) are proposed as an early prognostic factor of the disease. Growing attention is directed towards brain volume evaluation as a possible marker of the severity of MS. Previous studies found that MS patients lacking OB have less brain atrophy. AIM: to evaluate a possible relationship between OB and cerebral volume in a cohort of early MS patients. METHODS: Inclusion criteria were: diagnosis of relapsing-remitting MS; CSF analysis and MRI acquired simultaneously and within 12 months from clinical onset. A total of 15 healthy controls underwent MRI. RESULTS: In 20 MS patients, CSF analysis did not show OB synthesis (OB negative group). A control group of 25 MS patients in whom OB was detected was also randomly recruited (OB positive group). T test showed a significant difference in NWV between the OB positive and OB negative groups (P value = 0.01), and between the OB positive group and the healthy controls (P value = 0.001). No differences were detected between OB negative group and healthy controls. Multivariable linear regression showed a relationship between NWV and OB synthesis (P value = 0.02) controlling for age, gender, and EDSS. CONCLUSIONS: Our preliminary results suggest that OB positive patients show more atrophy of white matter since early phases of the disease, supporting the role of CSF analysis as a prognostic factor in MS.
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Encéfalo/patología , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/patología , Bandas Oligoclonales/líquido cefalorraquídeo , Sustancia Blanca/patología , Adulto , Atrofia/patología , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Pronóstico , Sustancia Blanca/diagnóstico por imagenRESUMEN
BACKGROUND: Several correlations between cognitive impairment (CI), radiologic markers and cognitive reserve (CR) have been documented in MS. OBIECTIVE: To evaluate correlation between CI and brain volume (BV) considering CR as possibile mitigating factor. METHODS: 195 relapsing MS patients underwent a neuropsychological assessment using BICAMS. BV was estimated using SIENAX to obtain normalized volume of brain (NBV), white matter (NWV), gray matter (NGV) and cortical gray matter (CGV). CR was estimated using a previously validated tool. RESULTS: Pearson test showed a correlation between the symbol digit modality test (SDMT) score and NBV (r=0.38; p<0.000) NGV(r=0.31; p<0.000), CGV (r=0.35; p<0.000) and CRI score(r=0.42; p<0.000). Linear regression (dependent variable:SDMT) showed a relationship with CR scores (p=0.000) and NGV(p<0.000). A difference was detected between cognitive impaired and preserved patients regarding mean of NBV(p=0.002), NGV(p=0.007), CGV(p=0.002) and CR Scores (p=0.007). Anova showed a association between the presence of CI (dependent variable) and the interaction term CRIQ × CGV (p=0.004) whit adjustment for age and disability evaluated by EDSS. CONCLUSIONS: Our study shows a correlation between cognition and BV, in particular gray matter volume. Cognitive reserve is also confirmed as an important element playing a role in the complex interaction to determine the cognitive functions in MS.
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Encéfalo/patología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Reserva Cognitiva/fisiología , Esclerosis Múltiple/complicaciones , Adulto , Encéfalo/diagnóstico por imagen , Trastornos del Conocimiento/diagnóstico por imagen , Evaluación de la Discapacidad , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/tratamiento farmacológico , Pruebas Neuropsicológicas , Análisis de RegresiónRESUMEN
The classification of peripheral T-cell lymphomas (PTCL) is still a matter of debate. To establish a molecular classification of PTCL, we analysed 59 primary nodal T-cell lymphomas using cDNA microarrays, including 56 PTCL and three T-lymphoblastic lymphoma (T-LBL). The expression profiles could discriminate angioimmunoblastic lymphoma, anaplastic large-cell lymphoma and T-LBL. In contrast, cases belonging to the broad category of 'PTCL, unspecified' (PTCL-U) did not share a single molecular profile. Using a multiclass predictor, we could separate PTCL-U into three molecular subgroups called U1, U2 and U3. The U1 gene expression signature included genes known to be associated with poor outcome in other tumors, such as CCND2. The U2 subgroup was associated with overexpression of genes involved in T-cell activation and apoptosis, including NFKB1 and BCL-2. The U3 subgroup was mainly defined by overexpression of genes involved in the IFN/JAK/STAT pathway. It comprised a majority of histiocyte-rich PTCL samples. Gene Ontology annotations revealed different functional profile for each subgroup. These results suggest the existence of distinct subtypes of PTCL-U with specific molecular profiles, and thus provide a basis to improve their classification and to develop new therapeutic targets.
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Perfilación de la Expresión Génica , Ganglios Linfáticos/patología , Linfoma de Células T/genética , Linfoma de Células T/patología , Humanos , Linfoma de Células T/clasificación , Linfoma de Células T/diagnóstico , Reacción en Cadena de la Polimerasa , PronósticoRESUMEN
BACKGROUND: Notoriously the treatment of multiple sclerosis (MS) is based on the use of several different drugs, characterized by a diverse mechanism of action, efficacy and safety. Recently, progress has been made towards developing new oral immunotherapies, and dimethyl fumarate is the third oral agent approved for the treatment of relapsing-remitting forms. CASE: A 24-year-old patient, affected by relapsing remitting multiple sclerosis, started treatment in December 2014 with dimethyl fumarate. The common side effects (flushing and gastrointestinal events) of dimethyl fumarate occurred at the beginning of treatment, but resolved after 1 month. Six months later, the patient presented with serious recrudescence of the gastrointestinal event. In addition to this symptom, he had developed acute omphalitis-a very rare infection in adults. CONCLUSION: The pathogenic role of dimethyl fumarate to induce this rare infection was probably related to changes in immunological surveillance as well as to the irritant effect of this agent on the gastrointestinal epithelium. Therefore, post-marketing studies in clinical practice are still needed to provide the necessary long-term safety data.
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Dimetilfumarato/efectos adversos , Inmunosupresores/efectos adversos , Infecciones/etiología , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Ombligo , Pared Abdominal/diagnóstico por imagen , Dimetilfumarato/uso terapéutico , Estudios de Seguimiento , Humanos , Inmunosupresores/uso terapéutico , Infecciones/diagnóstico por imagen , Infecciones/patología , Masculino , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/patología , Tomografía , Adulto JovenRESUMEN
BACKGROUND: High-density DNA microarrays require automatic feature extraction methodologies and softwares. These can be a potential source of non-reproducibility of gene expression measurements. Variation in feature location or in signal integration methodology may be a significant contribution to the observed variance in gene expression levels. RESULTS: We explore sources of variability in feature extraction from DNA microarrays on Nylon membrane with radioactive detection. We introduce a mathematical model of the signal emission and derive methods for correcting biases such as overshining, saturation or variation in probe amount. We also provide a quality metric which can be used qualitatively to flag weak or untrusted signals or quantitatively to modulate the weight of each experiment or gene in higher level analyses (clustering or discriminant analysis). CONCLUSIONS: Our novel feature extraction methodology, based on a mathematical model of the radioactive emission, reduces variability due to saturation, neighbourhood effects and variable probe amount. Furthermore, we provide a fully automatic feature extraction software, BZScan, which implements the algorithms described in this paper.
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Perfilación de la Expresión Génica/instrumentación , Análisis de Secuencia por Matrices de Oligonucleótidos , Algoritmos , Animales , Proteínas de Arabidopsis/genética , Sesgo , Neoplasias de la Mama/química , Ligasas de Carbono-Oxígeno/genética , Análisis por Conglomerados , ADN de Neoplasias/genética , ADN de Plantas/genética , Densitometría , Análisis Discriminante , Humanos , Procesamiento de Imagen Asistido por Computador , Ratones , Nylons , Radioisótopos de Fósforo/análisis , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , Reproducibilidad de los Resultados , Procesamiento de Señales Asistido por Computador , Programas InformáticosRESUMEN
Frequently patients are started on hemodialysis after the placement of a central venous catheter (temporary or tunneled) in the internal jugular vein (IJV). Currenty this procedure is facilitated by ultrasound probes that improve the rate of success of catheter placement in vessels and diminishes the possible complications, minimizing the gap between nephrologists with wide surgical expertise and those with limited surgical experience. Stenosis and thrombosis of the subclavia vein are well documented complications derived from the placement of the venous catheter. Internal jugular vein thrombosis is not seen very often due to scarce clinical evidence. In our paper we have been able to systematically document various extrinsic thrombotic complications outside the central venous catheter, by use of ultrasound (periluminar or related to the vessel).
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The authors describe a rare case of hepatocellular carcinoma that metastasized to the pectineal muscle of the right thigh. The patient had been treated with surgical procedures and with multiple sessions of transarterial chemoembolization, one of which was complicated by a right femoral artery hematoma at the catheter insertion site. It is unclear whether the muscle metastasis was caused by blood-borne spread or by tumor-cell seeding caused by the TACE procedure.
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Preparations of DNA from wheat (Triticum aestivum, cv Chinese Spring), barley (Hordeum vulgare, cv Betzes) and six euplasmic wheat-barley addition lines were digested to completion with restriction endonucleases and the products probed by Southern blot analysis using a cDNA-encoding barley (1-->3, 1-->4)-beta-glucanase isoenzyme II. It is shown that one of the barley (1-->3, 1-->4)-beta-glucanase genes is located on chromosome 1.
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An immunological assay has been used to investigate the synthesis of (1-->3,1-->4)-beta-glucanase (EC 3.2.1.73) isoenzymes from isolated barley aleurone layers and scutella. Enzyme release from both tissues is enhanced by 1 micromolar gibberellic acid and 10 millimolar Ca(2+), although increases induced by gibberellic acid are observed only in the presence of Ca(2+). Isoenzyme I is synthesized predominantly in the scutellum, while isoenzyme II is synthesized exclusively in the aleurone. A third, putative isoenzyme III has been detected in significant proportions in scutellar secretions and may also be secreted from aleurone layers. Both gibberellic acid and Ca(2+) appear to preferentially enhance isoenzyme II secretion from the aleurone and isoenzyme III secretion from scutella. The patterns of isoenzyme secretion are suggestive of tissue-specific differences in expression of the genes which code for (1-->3,1-->4)-beta-glucanase isoenzymes. Qualitatively similar results were obtained with barley cultivars harvested in Australia and North America.
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Immunoglobulin (Ig) A and IgG are the principal immune effector molecules at mucosal surfaces and in blood, respectively. Mucosal IgA is polymeric and bound to secretory component, whereas serum IgG is monomeric. We have now produced IgA2/IgG1 hybrid antibodies that combine the properties of IgA and IgG. Antibodies with Calpha3 at the end of the IgG H chain resemble IgA and form polymers with J chain that bind the polymeric Ig receptor. Like IgG, the hybrid proteins activated complement and bound FcgammaRI and protein A. Though the hybrid proteins contained both Cgamma2 and Cgamma3, they have a short in vivo half-life. Surprisingly, this decreased half-life correlated with a higher avidity than that of IgG for murine FcRn. Interestingly, antibodies with Calpha1 replacing Cgamma1 were resistant to extremes of pH, suggesting that Calpha1 increases antibody stability. These results provide insights into engineering antibodies with novel combinations of effector functions.