466 research outputs found
Abstract en Concreet
Abstract en concreet, laat ik zo concreet mogelijk beginnen. Twee jaar geleden werd
meneer Vere naar onze polikliniek verwezen. Zijn naam heb ik aangepast om
herkenning te voorkomen. Zijn huisarts had hem verwezen i.v.m. moeheidsklachten en
een afwijkend aantal witte bloedcellen. Aanvullend onderzoek van bloed en beenmerg
in ons laboratorium toonde inderdaad een hoog aantal witte bloedcellen zowel in bloed
als in het beenmerg. Het bleken echter geen volwassen, uitgerijpte cellen te zijn, maar
voorlopers daarvan, zeer jonge cellen, misschien zelfs wel stamcellen (Figuur 1). Links
kijkt u met mij door de microscoop naar normaal beenmerg met alle verschillende
bloed- en beenmerg-celtypen en rechts ziet u dat de normale cellen zijn verdrongen door
een agressieve woekering van leukemiecellen. De diagnose werd gesteld op een acute
leukemie en meneer Vere kreeg een intensieve behandeling aangeboden bestaande
uit een combinatie van meerdere celdodende middelen (cytostatica). Dit leidde
weliswaar tot het terugdringen van de leukemie, maar met fi jngevoelige technieken
konden we nog steeds activiteit van de leukemie aantonen. Het was duidelijk dat
aanvullende behandeling noodzakelijk zou zijn om tot definitieve genezing te komen.
De mogelijkheden van een bloedstamceltransplantatie werden overwogen, maar er
bleek geen passende donor in de familie en ook een passende, vrijwillige volwassen
donor uit de wereldwijde donorbank bleek niet te vinden. Uiteindelijk vonden wij
in de bloedbank van New York een navelstrengbloed-transplantaat, dat wel bleek te
passen en ook voldoende bloedvormende stamcellen leek te bevatten.Rede, uitgesproken ter gelegenheid van het aanvaarden van het ambt van Hoogleraar in de Haematopoietische Stamceltransplantatie aan het Erasmus MC, faculteit van de Erasmus Universiteit Rotterdam, op 1 september 200
Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome
Between 1988 and 1999, 127 patients with poor-risk acute lymphoblastic
leukemia (ALL) received a matched unrelated donor transplant using marrow
procured by National Marrow Donor Program (NMDP) collection centers and
sent out to 46 transplant centers worldwide. Poor risk was defined by the
presence of the translocations t(9;22) (n = 97), or t(4;11) (n = 25), or
t(1;19) (n = 5). Sixty-four patients underwent transplantation in first
remission (CR1), 16 in CR2 or CR3, and 47 patients had relapsed ALL or
primary induction failure (PIF). Overall survival at 2 years from
transplant was 40% for patients in CR1, 17% in CR2/3, and 5% in PIF or
relapse. Treatment-related mortality (TRM) and relapse mortality,
estimated as competing risk factors, were 54% and 6%, respectively, in
CR1, 75% and 8% in CR2/3, and 64% and 31% in PIF or relapse. Currently 23
CR1 patients are alive and free of disease with a median follow-up of 24
months (range, 3-97). Multivariable analysis showed that CR1, shorter
interval from di
Development of a real-time quantitative assay for detection of Epstein-Barr virus
With the use of real-time PCR, we developed and evaluated a rapid,
sensitive, specific, and reproducible method for the detection of
Epstein-Barr virus (EBV) DNA in plasma samples. This method allowed us to
screen plasma and serum samples over a range between 100 and 10(7) copies
of DNA per ml using two sample preparation methods based on absorption. A
precision study yielded an average coefficient of variation for both
methods of less than 12%, with a coefficient of regression for the
standard curve of a minimum of 0. 98. We detected EBV DNA in 19.2% of
plasma samples from immunosuppressed solid-organ transplant patients
without symptoms of EBV infections with a mean load of 440 copies per ml.
EBV DNA could be detected in all transplant patients diagnosed with
posttransplant lymphoproliferative disorder, with a mean load of 544,570
copies per ml. No EBV DNA could be detected in healthy individuals in
nonimmunosuppressed control groups and a mean of 6,400 copies per ml could
be detected in patients with infectious mononucleosis. Further studies
revealed that the inhibitory effect of heparinized plasma could be
efficiently removed by use of an extraction method with Celite as the
absorbent
An in vitro model for cytogenetic conversion in CML. Interferon-alpha preferentially inhibits the outgrowth of malignant stem cells preserved in long-term culture
IFN-alpha has been shown to prolong survival in chronic myeloid leukemia
patients, but its mechanism of action is still not understood. The human
cobblestone area-forming cell (CAFC) assay allows for the measurement of
the concentration of normal as well as malignant stem cells, while their
progeny can be measured in parallel long-term culture (LTC) in flasks
Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection
Recovery of cytomegalovirus (CMV)-specific T-cell-mediated immunity after
allogeneic hematopoietic stem cell transplantation (SCT) is critical for
protection against CMV disease. The study used fluorochrome-conjugated
tetrameric complexes of HLA-A2 molecules loaded with the immunodominant
NLVPMVATV (NLV) peptide derived from the CMV protein pp65 to quantify
A2-NLV-specific CD8+ T cells in partially T-cell-depleted grafts
administered to 27 HLA-A*0201+ patients and to monitor recovery of these T
cells during the first 12 months after SCT. None of the 9 CMV-seronegative
patients became infected with CMV, whereas 14 of 18 CMV-seropositive
patients developed CMV antigenemia after SCT. CMV-seropositive recipients
of grafts from CMV-seronegative donors required more preemptive treatment
with ganciclovir (GCV) than those of grafts from CMV-seropositive donors
(3 [1-6] versus 1 [0-3] courses, respectively; P =.009). The number of
A2-NLV-specific CD8+ T cells in the grafts correlated inversely with the
number of preemptive GCV courses administered (r = -0.61; P =.01). None of
the 9 CMV-seronegative patients mounted a CMV-specific immune response as
measured by monitoring A2-NLV-specific CD8+ T cells after SCT. Thirteen of
14 CMV-seropositive patients without CMV disease recovered these T cells.
In spite of preemptive GCV treatment, CMV disease developed in 4 patients,
who all failed to recover A2-NLV-specific CD8+ T cells after SCT (P
=.002). Thus, enumeration of HLA-restricted, CMV-specific CD8+ T cells in
the grafts and monitoring of these T cells after SCT may constitute a
rapid and sensitive tool to identify SCT recipients at risk for developing
CMV disease
Etanercept for steroid-refractory acute graft-versus-host disease
Background: Acute graft-versus-host disease (aGVHD) is an important complication of allogeneic stem cell transplantation (alloSCT). High dose glucocorticosteroids, are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients. No standard second-line regimen has been established. Different options have been reported, including anti-TNFα antibodies. Methods: We retrospectively reviewed the outcome of 15 patients with steroid-refractory (SR) aGVHD treated with etanercept at our institution. Patients were transplanted for a hematological malignancy and received either a myeloablative or a non-myeloablative conditioning regimen. Prophylaxis of GVHD consisted of cyclosporin A and mycophenolic acid. Results: Acute GVHD was diagnosed at a median of 61 days post-transplantation. All patients had grade III aGVHD of the gut. Second-line treatment with etanercept was started at a median of 13 days after initiation of first-line therapy. Overall response rate was 53%, with CR in 3 patients and PR in 5 patients. Median overall survival after initiation of treatment with etanercept was 66 days (range 5–267) for the entire group. Median overall survival was 99 days (range 47–267 days) for responders and 17 days (range 5–66 days) for non-responders (p<0.01). Nevertheless, all patients died. Causes of death were progressive GVHD in 7 patients (47%), infection in 6 patients (40%), cardiac death in 1 patient (6.7%) and relapse in 1 patient (6,7%). Conclusion: Second-line treatment with etanercept does induce responses in SR-aGVHD of the gut but appears to be associated with poor long-term survival even in responding patients
Varkansen : springplank naar een duurzame veehouderij : varkenshouderij met neus voor dier, ondernemer, milieu en burger-consument
'Varkansen' laat ontwerpen van integraal duurzame varkenshouderij zien. Aanleiding is de 'Toekomstvisie op de duurzame veehouderij'. Daarin staat dat de veehouderij over 15 jaar duurzaam moet zijn, dus produceert met respect voor mens, dier en milieu
Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients
During a 17-month period, we performed retrospective analyses of the prevalence of and clinical symptoms associated with human metapneumovirus (hMPV) infection, among patients in a university hospital in The Netherlands. All available nasal-aspirate, throat-swab, sputum, and bronchoalveolar-lavage samples (N=1515) were tested for hMPV RNA by reverse-transcriptase polymerase chain reaction. hMPV RNA was detected in 7% of samples from patients with respiratory tract illnesses (RTIs) and was the second-most-detected viral pathogen in these patients during the last 2 winter seasons. hMPV was detected primarily in very young children and in immunocompromised individuals. In young children, clinical symptoms associated with hMPV infection were similar to those associated with human respiratory syncytial virus (hRSV) infection, but dyspnea, feeding difficulties, and hypoxemia were reported more frequently in hRSV-infected children. Treatment with antibiotics and corticosteroids was reported more frequently in hMPV-infected children. From these data, we conclude that hMPV is an important pathogen associated with RTI
Yap1-Driven Intestinal Repair Is Controlled by Group 3 Innate Lymphoid Cells
Intestinal repair is driven by epithelial stem cells, but how these stem cells are instructed to initiate repair was unknown. Here, Romera-Hernández et al. report that epithelial proliferation after damage is independent of the stem cell-protective signal IL-22 but requires ILC3-dependent amplification of regenerative YAP1 signaling in stem cells.Tissue repair requires temporal control of progenitor cell proliferation and differentiation to replenish damaged cells. In response to acute insult, group 3 innate lymphoid cells (ILC3s) regulate intestinal stem cell maintenance and subsequent tissue repair. ILC3-derived IL-22 is important for stem cell protection, but the mechanisms of ILC3-driven tissue regeneration remain incompletely defined. Here we report that ILC3-driven epithelial proliferation and tissue regeneration are independent of IL-22. In contrast, ILC3s amplify the magnitude of Hippo-Yap1 signaling in intestinal crypt cells, ensuring adequate initiation of tissue repair and preventing excessive pathology. Mechanistically, ILC3-driven tissue repair is Stat3 indepe
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