Pancytopenia related to low-dose methotrexate: study of five cases and review of the literature

PURPOSE: The aim of this study is to report personal experience of pancytopenia related to low-dose methotrexate and to review the literature. METHODS: We included retrospectively all cases of pancytopenia related to low-dose methotrexate (<25 mg/week), followed between January 1997 and December 2006, in the university hospital of Strasbourg, France. RESULTS: Five women, mean age 75.6 years, were included in the present study. Clinical manifestations included: symptomatic anemia (n=4), infection (n=3) and hemorrhagic manifestations (n=2); one patient had no feature. Mean hemoglobin concentration was 8,8 g/dl; mean white cell and platelet counts were 1,500 /mm(3) and 16,000 /mm(3), respectively. Potential risk factors were identified in all patients: renal failure and low serum albumin levels (n=5), anti-inflammatory drug intake (n=2), folate deficiency (n=4) and cobalamin deficiency (n=1). One patient died of septic and hemorrhagic cerebral complications. CONCLUSION: Pancytopenia related to tow-dose methotrexate is a rare but life-threatening disorder. Search and prevention of potential risk factors are required in all patients; determination of MTHFR genotype may be of several interests as folate supplementation.     

Phyllodes tumour of the seminal vesicle - case report of a rare tumour entity

Neoplasms of the seminal vesicles are rare. Here we report on a patient with a low-grade phyllodes tumour of the seminal vesicle. The patient was admitted to our hospital with a tumour in the excavatio rectovesicalis diagnosed by CT scan. He had no symptoms. For further diagnosis we took transrectal ultrasound-guided biopsies, the histopathological examination showed no malignant features. One month later a follow-up CT scan demonstrated a significant enlargement of the tumour. Therefore we decided to perform a surgical exploration. During surgery we found a partially necrotic mass involving the prostate, the urinary bladder and the rectum. Both radical cystoprostatectomy with ileal conduit and anterior resection of the rectum with colostomy were necessary. Histologically the specimen showed a low-grade phyllodes tumour of the left seminal vesicle. One year after surgery the follow-up was completely normal without any residual or recurrent tumour. Frequency, histology, diagnostic investigations, therapy and prognosis of this rare tumour entity are discussed with respect to the actual literature.     

AID expression levels determine the extent of cMyc oncogenic translocations and the incidence of B cell tumor development

Immunoglobulin (Ig) isotype switching is a recombination event that changes the constant domain of antibody genes and is catalyzed by activation-induced cytidine deaminase (AID). Upon recruitment to Ig genes, AID deaminates cytidines at switch (S) recombination sites, leading to the formation of DNA breaks. In addition to their role in isotype switching, AID-induced lesions promote Igh-cMyc chromosomal translocations and tumor development. However, cMyc translocations are also present in lymphocytes from healthy humans and mice, and thus, it remains unclear whether AID directly contributes to the dynamics of B cell transformation. Using a plasmacytoma mouse model, we show that AID^+/− mice have reduced AID expression levels and display haploinsufficiency both in the context of isotype switching and plasmacytomagenesis. At the Ig loci, AID^+/− lymphocytes show impaired intra- and inter-switch recombination, and a substantial decrease in the frequency of S mutations and chromosomal breaks. In AID^+/− mice, these defects correlate with a marked decrease in the accumulation of B cell clones carrying Igh-cMyc translocations during tumor latency. These results thus provide a causality link between the extent of AID enzymatic activity, the number of emerging Igh-cMyc–translocated cells, and the incidence of B cell transformation.     

Mast cell-expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis

Mast cells contribute importantly to both protective and pathological IgE-dependent immune responses. We show that the mast cell-expressed orphan serpentine receptor mCCRL2 is not required for expression of IgE-mediated mast cell-dependent passive cutaneous anaphylaxis but can enhance the tissue swelling and leukocyte infiltrates associated with such reactions in mice. We further identify chemerin as a natural nonsignaling protein ligand for both human and mouse CCRL2. In contrast to other "silent" or professional chemokine interreceptors, chemerin binding does not trigger ligand internalization. Rather, CCRL2 is able to bind the chemoattractant and increase local concentrations of bioactive chemerin, thus providing a link between CCRL2 expression and inflammation via the cell-signaling chemerin receptor CMKLR1.     

Image analysis of time-lapse movies--a precision control guided approach to correct motion artefacts

In long-term time-lapse studies of cell migration, it is often important to distinguish active movement of individual cells from global tissue motion caused, for instance, by morphogenetic changes, or due to artefacts. We have developed a method to define and correct global movements. This is realized by the sequential morphing of image sequences to the initial image based on the position of immobile reference objects. Technically, the approach is implemented in ImageJ, using the plugin UnwarpJ. We describe an efficient way to select parameter settings such as to optimize image correction. To this end, we implemented a strict statistical control that allows to quantify image registration quality. We document this approach using a time-lapse sequence of migrating interneurons in slice cultures of the developing cerebellum.