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141.
Boers-Sonderen MJ Desar IM Blokx W Timmer-Bonte JN van Herpen CM 《Anti-cancer drugs》2012,23(7):761-764
In melanoma, the RAS/RAF/MEK/ERK pathway is frequently activated by mutations in BRAF and NRAS. Selumetinib (AZD6244) is an oral, selective, non-ATP-competitive inhibitor of MEK1/2. Here, we describe a patient with metastatic melanoma (T1N2cM1a) with a BRAF V600E mutation. She is currently being treated with selumetinib 75 mg twice daily in a phase I trial and has shown complete response for the past 4 years. This case report raises questions regarding treatment schedule, treatment duration and management of adverse events. 相似文献
142.
143.
Blokx WA Andriessen MP van Hamersvelt HW van Krieken JH 《The American Journal of dermatopathology》2002,24(5):414-422
Primary cutaneous posttransplantation B-cell lymphoproliferative disorder is rare. The few previously reported patients were all treated with surgery, radiotherapy, or lowering of immunosuppression. We describe a 65-year-old woman presenting with an intermammary skin ulcer 21 years after renal transplantation, proving on biopsy to be an Epstein Barr virus (EBV)-related posttransplantation B-cell lymphoproliferative disorder. A few weeks later, the skin ulcer showed complete clinical regression. Hematologic staging evaluation showed no evidence of extracutaneous involvement. Despite continuation of immunosuppression, the patient stayed free of disease until 18 months after initial diagnosis, when she developed a progressive hemiparesis and died of acute myocardial infarction. At autopsy, a recurrent B-cell posttransplantation lymphoproliferative disorder in the left side of the thalamus region (measuring 1 x 0.8 cm) was established. The long interval between the primary cutaneous lesion and the localized brain recurrence supports primary skin posttransplantation lymphoproliferative disorder, especially because the patient was not treated for her posttransplantation lymphoproliferative disorder. Review of the literature on primary cutaneous posttransplantation B-cell lymphoproliferative disorder and this case gives the impression that cutaneous posttransplantation B-cell lymphoproliferative disorders of B-cell lineage behave in a more benign manner than identical lesions arising extracutaneously. Because of the rare occurrence of posttransplantation B-cell lymphoproliferative disorder primarily involving the skin, extracutaneous origin should be excluded. If B-cell lineage can be established, EBV is present, alterations in oncogenes or tumor suppressor genes associated with malignant lymphoma are absent, and bcl-6 gene mutation associated with progression is absent, initially aggressive treatment might be avoided. However, long-term clinical follow-up with prolonged maintenance therapy (reduction of immunosuppression or antiviral therapy) for prevention of recurrent posttransplantation lymphoproliferative disorder seems indicated, as is demonstrated by the case reported in the current study. 相似文献
144.
de Jongh GJ Zeeuwen PL Kucharekova M Pfundt R van der Valk PG Blokx W Dogan A Hiemstra PS van de Kerkhof PC Schalkwijk J 《The Journal of investigative dermatology》2005,125(6):1163-1173
Recently, it was shown that lesional skin of atopic dermatitis patients expresses low levels of some antimicrobial peptides, compared with psoriasis patients. Here we performed microarray analysis on mRNA from purified lesional epidermal cells of patients with chronic plaque psoriasis and chronic atopic dermatitis, to investigate whether this is a general phenomenon for host defense proteins, and how specific it is for this class of molecules. Microarray data were confirmed on a selected set of genes by quantitative PCR and at the protein level by immunohistochemistry. We found overexpression of many antimicrobial proteins in keratinocytes from psoriatic skin compared with atopic dermatitis skin. Interestingly, we observed that markers of normal differentiation and the activated/hyperproliferative epidermal phenotype were expressed at equal levels. Chronic lesions of psoriasis and atopic dermatitis patients are remarkably similar with respect to cellular proliferation. We conclude that psoriatic epidermis expresses high levels of host defense proteins compared with atopic dermatitis epidermis, and this phenomenon appears to be specific for these proteins. It remains to be investigated whether this is caused by genetic polymorphisms in pathways leading to an epidermal antimicrobial response, or by differences in the cellular infiltrate in psoriasis compared with atopic dermatitis. 相似文献
145.
Zhang W Walboomers XF Van Kuppevelt TH Daamen WF Van Damme PA Bian Z Jansen JA 《Journal of tissue engineering and regenerative medicine》2008,2(2-3):117-125
An increasing number of investigations supports that adult stem cells have the potential to differentiate into matured cell types beyond their origin, a property defined as plasticity. Previously, the plasticity of stem cells derived from dental pulp (DPSC) has been confirmed by culturing cells in lineage-specific media in vitro. In the current study, the in vivo differentiation or maturation potential of DPSC was further analysed, by transplanting human DPSC/collagen scaffold constructs into subcutaneous tissue of immunocompromised mice. Cells received odontogenic, adipogenic or myogenic pre-induction, whereas control samples received no stimulation. Also blank collagen scaffolds were implanted. The results indicated that seeded cells produced tissue within the implanted constructs after 3 weeks of implantation. According to morphological and phenotypical changes, the pre-induced DPSC showed the ability to further differentiate along odontogenic, myogenic and adipogenic pathways in vivo. Moreover, DPSC without pre-treatment were able to spontaneously differentiate along odontogenic and adipogenic directions in vivo. However, only limited mature morphological changes were detected in histology. In summary, stem cells derived from human dental pulp form a suitable source for tissue engineering and cell-mediated therapy, although additional analyses should be considered. 相似文献
146.
Gibbons HM Hughes SM Van Roon-Mom W Greenwood JM Narayan PJ Teoh HH Bergin PM Mee EW Wood PC Faull RL Dragunow M 《Journal of neuroscience methods》2007,166(1):89-98
Microglia and astrocytes play vital roles in normal human brain function and in neurological disorders. To study their physiological and pathological roles it is desirable to establish in vitro systems that are derived from the adult human brain. Although several groups have successfully cultured cells from the human brain, the composition of these cultures remains controversial. Using morphological criteria, immunocytochemical analysis and a BrdU incorporation assay we demonstrate the presence of poorly proliferative microglia and astrocytes in cultures derived from epilepsy biopsy tissue. In addition, we characterized a third cell type as fibronectin and prolyl 4-hydroxylase immunopositive fibroblast-like cells, which are highly proliferative and become the predominant cell type after successive sub-culturing. Therefore, although cultures from adult human brain tissue provide an excellent resource for studying human glial cells, careful consideration must be given to their cellular composition when performing studies using these methods. 相似文献
147.
Willeke P Gaubitz M Schotte H Becker H Mickholz E Domschke W Schlüter B 《Rheumatology (Oxford, England)》2007,46(3):479-483
OBJECTIVES: To analyse the prevalence of alpha-fodrin antibodies in patients with primary (pSS) and secondary Sj?gren's syndrome (sSS) and the relation to clinical, serological and immunological features. METHODS: Serum IgA and IgG antibodies to the 120 kDa alpha-fodrin were determined by ELISA technique in 62 pSS patients and 28 sSS patients. Results were correlated with clinical symptoms and laboratory findings as well as with the HLA-DR genotype. Additionally, antibody concentrations were correlated with the numbers of peripheral blood mononuclear cells (PBMCs) secreting interleukin (IL)-6, IL-10, interferon-gamma (INF)-gamma, and tumour necrosis factor-alpha determined by ELISPOT analysis. Lymphocytes and monocytes were examined flow-cytometrically for the expression of activation markers. Healthy age- and sex-matched volunteers served as controls. RESULTS: The sensitivity of IgA and IgG alpha-fodrin antibodies was 35 and 31%, respectively, in pSS patients. In sSS patients, the sensitivity was 29 and 21%, respectively. In pSS patients with IgG antibodies, recurrent parotid swelling was significantly more prevalent. Also the number of INF-gamma secreting PBMCs and the percentage of CD4/CD71+ lymphocytes as well as CD14/HLA-DR+ monocytes were significantly increased in this group compared with alpha-fodrin-negative patients or with controls. Interestingly, these patients also had a shorter disease duration. No association of alpha-fodrin antibodies with the HLA-DR genotype was found. CONCLUSION: Due to the low prevalence, serum antibodies to alpha-fodrin turned out to be of limited diagnostic value in our study. However, our data suggest that IgG antibodies to alpha-fodrin are indicative of clinical and immunological activity in pSS especially in patients with shorter disease duration and may thus serve as a marker of disease activity. 相似文献
148.
BACKGROUND: Platelet (PLT) storage lesions might depend on the total PLT count in the storage container and also on the PLT pooling system, especially the storage container, that is used for preparation of PLT concentrates (PCs). In this study, the PLT capacity of four commercially available PLT pooling systems was studied. MATERIALS AND METHODS: Four PCs were prepared in pooling systems of Baxter, Fresenius, Terumo, or Pall. The PCs were pooled and divided with various total PLT counts over the four storage containers (<225 × 109, 225 × 109‐324 × 109, 325 × 109‐424 × 109, and >424 × 109 PLTs). Volumes were kept equal by adding plasma to PCs with less than 425 × 109 PLTs until a same volume as for PCs with more than 424 × 109 PLTs was reached. PCs were stored at room temperature and tested for various in vitro variables on Days 1, 3, 5, 7, and 9. Paired experiments were repeated for each system five times. RESULTS: In vitro variables remained good for 9 days, that is, swirling score of 2 or more, pH value of 6.8 or more, glucose level of 10 mmol per L or more, lactate level of less than 25 mmol per L, and CD62p expression of less than 50 percent, for PCs in Baxter systems with more than 225 × 109 PLTs, for PCs in Fresenius and Terumo systems with 225 × 109 to 424 × 109 PLTs, and for PCs in Pall systems with fewer than 425 × 109 PLTs. CONCLUSION: PLT capacity depended on the PLT pooling systems used. All systems provide acceptable storage conditions. The Baxter system was the only system with capacity for more than 424 × 109 PLTs per PC. 相似文献
149.
Heidi V. N. Küsters-Vandevelde Ilse A. C. H. van Engen-van Grunsven Benno Küsters Marcory R. C. F. van Dijk Patricia J. T. A. Groenen Pieter Wesseling Willeke A. M. Blokx 《Acta neuropathologica》2010,120(6):755-764
The histological differential diagnosis between melanotic schwannoma, primary leptomeningeal melanocytic lesions and cellular
blue nevus can be challenging. Correct diagnosis of melanotic schwannoma is important to select patients who need clinical
evaluation for possible association with Carney complex. Recently, we described the presence of activating codon 209 mutations
in the GNAQ gene in primary leptomeningeal melanocytic lesions. Identical codon 209 mutations have been described in blue nevi. The aims
of the present study were to (1) perform a histological review of a series of lesions (initially) diagnosed as melanotic schwannoma
and analyze them for GNAQ mutations, and (2) test the diagnostic value of GNAQ mutational analysis in the differential diagnosis with leptomeningeal melanocytic lesions. We retrieved 25 cases that were
initially diagnosed as melanotic schwannoma. All cases were reviewed using established criteria and analyzed for GNAQ codon 209 mutations. After review, nine cases were classified as melanotic schwannoma. GNAQ mutations were absent in these nine cases. The remaining cases were reclassified as conventional schwannoma (n = 9), melanocytoma (n = 4), blue nevus (n = 1) and lesions that could not be classified with certainty as melanotic schwannoma or melanocytoma (n = 2). GNAQ codon 209 mutations were present in 3/4 melanocytomas and the blue nevus. Including results from our previous study in leptomeningeal
melanocytic lesions, GNAQ mutations were highly specific (100%) for leptomeningeal melanocytic lesions compared to melanotic schwannoma (sensitivity
43%). We conclude that a detailed analysis of morphology combined with GNAQ mutational analysis can aid in the differential diagnosis of melanotic schwannoma with leptomeningeal melanocytic lesions. 相似文献
150.
Dumas EM Versluis MJ van den Bogaard SJ van Osch MJ Hart EP van Roon-Mom WM van Buchem MA Webb AG van der Grond J Roos RA;TRACK-HD investigators 《NeuroImage》2012,61(3):558-564
Increased iron in subcortical structures in patients with Huntington's Disease (HD) has been suggested as a causal factor of neuronal degeneration. The present study examines iron accumulation, measured using magnetic resonance imaging (MRI), in premanifest gene carriers and in early HD patients as compared to healthy controls. In total 27 early HD patients, 22 premanifest gene carriers and 25 healthy controls, from the Leiden site of the TRACK-HD study, underwent 3T MRI including high resolution 3D T(1)- and T(2)-weighted and asymmetric spin echo (ASE) sequences. Magnetic Field Correlation (MFC) maps of iron levels were constructed to assess magnetic field inhomogeneities and compared between groups in the caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, accumbens nucleus, and thalamus. Subsequently the relationship of MFC value to volumetric data and disease state was examined. Higher MFC values were found in the caudate nucleus (p<0.05) and putamen (p<0.005) of early HD compared to controls and premanifest gene carriers. No differences in MFC were found between premanifest gene carriers and controls. MFC in the caudate nucleus and putamen is a predictor of disease state in HD. No correlation was found between the MFC value and volume of these subcortical structures. We conclude that Huntington's disease patients in the early stages of the disease, but not premanifest gene carriers, have higher iron concentrations in the caudate nucleus and putamen. We have demonstrated that the iron content of these structures relates to disease state in gene carriers, independently of the measured volume of these structures. 相似文献