Aberrant Platelet Aggregation as Initial Presentation of Essential Thrombocythemia: Failure of Entero-Coated Aspirin to Reduce Platelet Hyperactivation.

Essential thrombocythemia (ET) is a myeloproliferative neoplasm variant characterized by excessive production of platelets. Since the most common cause of mortality and morbidity in ET patients is thrombosis, the excessive production of platelets may cause thrombotic events. However, little is known about the function of platelets in ET.

Inter-laboratory method validation of CD34+ flow-cytometry assay: the experience of Turin Metropolitan Transplant Centre.

The Turin Metropolitan Transplant Centre (CIC 305) includes four flow-cytometry laboratories assessing quality control on hematopoietic stem cells (HSC) with different instruments and operators. Therefore, the CD34+ enumeration assay should be validated on a regular basis. We describe here the validation plan to test the inter-laboratory reproducibility of CD34+ enumeration assay, based on the risk analysis.

Tailoring Rituximab According to CD27-Positive B-Cell versus CD19-Positive B-Cell Monitoring in Neuromyelitis Optica Spectrum Disorder and MOG-Associated Disease: Results from a Single-Center Study.

Introduction: B-cell-depleting agents have been widely used for neuromyelitis optica spectrum disorder (NMOSD) and MOG-associated diseases (MOGAD), but no consensus exists on the optimal dose and frequency of treatment administration. The aim of our study was to evaluate the effect of a Rituximab (RTX) personalized treatment approach based on CD27-positive B-cell monitoring on efficacy, safety, and infusion rates.

Methods: This is a retrospective, uncontrolled, single-center study including patients with NMOSD and MOGAD treated with RTX at a tertiary multiple sclerosis center at the San Luigi University Hospital, Orbassano, Italy.

CD19 mRNA quantification improves rituximab treatment-to-target approach: a proof of concept study.

We compared pre-amplification (PA) RT-PCR blood CD19 mRNA quantification with flow cytometry (FC), to personalize rituximab re-treatment in neuromyelitis optica spectrum disorders (NMOSDs) patients. 47 blood samples from 3 NMOSDs patients were studied. PA-RT-PCR quantified CD19 in all samples, and a positivity threshold was defined, whereas CD19+ B cells were under threshold in 31/47 samples by FC.

C-reactive protein levels in the first days of life: a systematic statistical approach.

Objective: Microbial neonatal infections are responsible for considerable morbidity and mortality and for this reason there is a growing interest for new approaches in the clinical government of this human affection. Using an integrated statistical model, this work investigated the role of the C-reactive protein (CRP) in the diagnosis of sepsis and therapy assessment in newborns admitted in neonatal intensive care unit.

Methods: 386 newborns admitted in neonatal intensive care unit were enrolled in this work.

The role of the laboratory in choosing antibiotics.

Objective: Antimicrobial resistance is one of the biggest problem in medicine at the beginning of the third millennium. Antibiotic resistance is frequently associated with significant morbidity, longer hospitalization, excess costs and mortality.

Methods: In this work we discussed the role of clinical microbiology laboratory as an essential part for an effective infection control program, especially in management and treatment of "difficult infections".

Prognostic relevance of cytometric quantitative assessment in patients with myelodysplastic syndromes.

Objectives: Morphology and cytogenetics are currently used to define prognosis in myelodysplastic syndromes (MDS). However, these parameters have some limits. Flow cytometry has been recently included in the diagnostic panel for MDS, and its prognostic significance is under evaluation.

Expression and pharmacological inhibition of thymidylate synthase and Src kinase in nonsmall cell lung cancer.

The combination of cytotoxic chemotherapy with signaling pathway inhibitors represents a potential strategy to improve the treatment of nonsmall cell lung cancer (NSCLC). Thymidylate synthase (TS) is an enzyme essential for DNA synthesis, and its overexpression has been associated with the reduced sensitivity to antifolate agents. Src is a tyrosine kinase that modulates the cytotoxicity of cancer cells after drug treatment, and in vitro data indicate that its inhibition could revert the resistance to TS-inhibiting drugs.

TCR transfer induces TCR-mediated tonic inhibition of RAG genes in human T cells.

Induction of the TCR signaling pathway terminates the expression of RAG genes, and a link between this pathway and their transcriptional control is evident from the recent demonstration of their re-expression if the TCR is subsequently lost or down-regulated. Since unstimulated T cells display a steady-state level of "tonic" TCR signaling, i.e.

[Deficit of cell-mediated immunity and Nocardia's infection. A case report].

We described the case of a patient, recently studied, that underwent immunosuppressive therapy for pemphigus vulgaris and then developed a Nocardia's infection. The case was severe and multiple localization in lungs and other organs was observed. The pathology was treated by using antibiotics, without autoimmunity secondary pathology.

Deferasirox is a powerful NF-kappaB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging.

Background: Usefulness of iron chelation therapy in myelodysplastic patients is still under debate but many authors suggest its possible role in improving survival of low-risk myelodysplastic patients. Several reports have described an unexpected effect of iron chelators, such as an improvement in hemoglobin levels, in patients affected by myelodysplastic syndromes. Furthermore, the novel chelator deferasirox induces a similar improvement more rapidly.

Effects of Src kinase inhibition induced by dasatinib in non-small cell lung cancer cell lines treated with cisplatin.

c-Src is a tyrosine kinase involved in tumor proliferation, migration, and angiogenesis and has been shown to modulate the cytotoxicity following cisplatin-induced DNA damages. c-Src is frequently activated in non-small cell lung cancer (NSCLC) tissues and cell lines, but no preclinical data regarding the effects of the novel potent Src inhibitor, dasatinib (BMS-354825), in the modulation of cisplatin resistance are currently available. The present study reports that treatment with dasatinib completely abrogated Src phosphorylation in the majority of the NSCLC cell lines tested (n = 7), with modest effects on cell proliferation and survival.

Neuroendocrine immunity in patients with Alzheimer's disease: toward translational epigenetics.

The emerging domain of epigenetics in molecular medicine finds application for a variety of patient populations. Here, we present fundamental neuroendocrine immune evidence obtained in patients with senile dementia of the Alzheimer's type (sDAT), and discuss the implications of these data from the viewpoint of translational epigenetics of Alzheimer's disease. We followed 18 subjects with mild sDAT treated with acetylcholinesterase inhibitors, and 10 control subjects matched for age in a repeated measure design every six months for 18 months.

Physiologic modulation of natural killer cell activity as an index of Alzheimer's disease progression.

Patients with Alzheimer's disease (AD) are characterized by an altered sensitivity to cortisol-mediated modulation of circulating lymphocytes. Longitudinal studies are needed to address the clinical applicability of these abnormalities as prognostic factors. Therefore, we designed a longitudinal study to address the clinical applicability of physiologic modulation of Natural Killer (NK) cell activity as a prognostic factor in AD.

Alternative BCR/ABL splice variants in Philadelphia chromosome-positive leukemias result in novel tumor-specific fusion proteins that may represent potential targets for immunotherapy approaches.

Imatinib currently represents the standard treatment in the early chronic phase of chronic myelogenous leukemia (CML), thanks to the high percentage of cytogenetic complete remission achieved, but it is yet unclear to what extent it can eradicate leukemia. Therefore, different vaccination strategies have been suggested, mainly based on the exploitment of the junctional peptides spanning the fusion region of the Bcr/Abl proteins. To identify new potential immunologic targets, 63 Philadelphia chromosome-positive patients and 6 BCR/ABL-positive cell lines were tested in nested reverse transcriptase PCR to detect the presence of BCR/ABL transcripts arising from the alternative splicing of the main BCR/ABL transcripts.

Unusual clinical presentation of Mycobacterium fortuitum infection in an immunocompetent woman.

The Mycobacterium fortuitum group of rapidly growing nontuberculous mycobacteria is an uncommon cause of renal infection, particularly in otherwise healthy hosts. We describe a case of nephritis due to M. fortuitum in an immunocompetent woman with a clinical and radiological diagnosis of renal tuberculosis.

Valproate enhances imatinib-induced growth arrest and apoptosis in chronic myeloid leukemia cells.

Background: The objective of this study was to evaluate the ability of the clinically available histone deacetylase (HDAC) inhibitor valproate to enhance the cytotoxicity of the Bcr-Abl inhibitor imatinib in imatinib-resistant cell lines.

Methods: Interactions between imatinib, and valproate have been examined in imatinib-sensitive and -resistant chronic myeloid leukemia (CML)cell lines (K562, KCL-22, CML-T1) and in bone marrow mononuclear cells (MNCs) derived from imatinib-resistant CML patients.

Results: In imatinib-sensitive cell lines, cotreatment with imatinib 0.

Increase in platelet count in older, poor-risk patients with acute myeloid leukemia or myelodysplastic syndrome treated with valproic acid and all-trans retinoic acid.

Background: The authors investigated the efficacy and safety of the histone deacetylase inhibitors valproic acid (VPA) and all-trans retinoic acid (ATRA) as differentiation agents in a cohort of older, poor-risk patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Methods: Twenty older patients with recurrent or refractory AML or MDS were treated in a Phase II protocol with sequential VPA and ATRA therapy. VPA was started at a dose of 10 mg/kg per day and then escalated to achieve the serum concentration of 45-100 microg/mL.