The analysis of chromosomal abnormalities provides significant prognostic information in patients with chronic lymphocytic leukaemia (CLL), a disease with a highly heterogeneous clinical course. Chromosomal abnormalities commonly found are trisomy 12, del(13)(q14), del(11)(q22-23), del(17)(p13) and del(6)(q21). Translocations are present in some patients and affect regions recurrently involved in CLL. This report describes the clinical and pathological characteristics of four CLL patients showing a new recurrent chromosomal abnormality dic(8;17)(p11;p11), that implied loss of the TP53 gene in all cases. In addition, TP53 gene was mutated in three out of four patients. Mechanically, Low Copy Repeats (LCR) in 17p12 and 8p11 may explain the origin of the translocation by non-allelic homologous recombination (NAHR). Isolated dic(8;17)(p11;p11) in patients with mutated IGHV genes status may not have the same prognostic impact as other mutations or deletions affecting the TP53 gene. Larger series are needed to better evaluate the clinical impact of this chromosomal aberration during the course of the disease. 相似文献
Pandemic A/H1N1 influenza emerged in Mexico at the end of March 2009. Since then, it is still important to provide evidences that contributed to the international spread of the virus and to ascertain the attack rate of this new strain of influenza among the first cases in Spain that led to identify the first transmission in Europe.
Methods
Three pandemic A/H1N1 influenza groups related to an overseas flight were studied: 71 student group, 94 remaining passengers, and 68 contacts of confirmed cases. The attack rate with their 95% confidence interval (CI) among the student group and contacts was calculated. On April 26th, when the first cases were notified, strong preventive measures were implemented among the student group and the contacts of the confirmed cases.
Results
On 27th April, the first pandemic A/H1N1 influenza cases confirmed in Spain were three students that came back from Mexico by airplane. A student generated the first native case in Spain and one of the first cases in Europe. Similar attack rates were found between the student group (14.1%; CI: 12.1–16.1) and their contacts (13.2%; CI: 4.4–22.0), but no cases among remaining passengers were detected, suggesting low transmission risk during air travel.
Conclusion
The first cases of pandemic A/H1N1 influenza in Spain were imported by airplane from Mexico. Preventive efforts to reduce the impact of the influenza influenced that primary and secondary rates were lower than first estimations by WHO. 相似文献
Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. We have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, we have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerization status of the nanoscale material, both regulatable by conventional protein engineering approaches. 相似文献
This article analyzes the concept of inactive fibrotic lesions of presumed tuberculous origin (old healed tuberculosis), defined by radiological characteristics and a positive tuberculin skin test (TST), and we examine the evidence-based foundation for the indication of treatment of latent tuberculosis infection in these cases. We explore the risk of reactivation in older and recent literature, and the problems raised by the differential diagnosis with active tuberculosis with negative bacteriology. We also analyze data on the prevalence of fibrotic lesions in the recent literature. We examine the possible role of Interferon Gamma Release Assays (IGRAs) versus TST and other molecular antigen detection techniques in sputum that can aid in establishing the diagnosis and we discuss the current indications for chemoprophylaxis and the different options available. We propose diagnostic guidelines and therapeutic algorithms based on risk stratification by age and other factors in the management of radiological lesions that raise a differential diagnosis between fibrotic lesions and active pulmonary tuberculosis with negative bacteriology. 相似文献
Malignant melanoma is a highly aggressive skin cancer characterized by an elevated grade of tumor cell plasticity. Such plasticity allows adaptation of melanoma cells to different hostile conditions and guarantees tumor
survival and disease progression, including aggressive features such as drug resistance. Indeed, almost 50% of
melanoma rapidly develop resistance to the BRAFV600E inhibitor vemurafenib, with fast tumor dissemination,
a devastating consequence for patients’ outcomes. Vasculogenic mimicry (VM), the ability of cancer cells to
organize themselves in perfused vascular-like channels, might sustain tumor spread by providing vemurafenibresistant cancer cells with supplementary ways to enter into circulation and disseminate. Thus, this research
aims to determine if vemurafenib resistance goes with the acquisition of VM ability by aggressive melanoma
cells, and identify a driving molecule for both vemurafenib resistance and VM. We used two independent
experimental models of drug-resistant melanoma cells, the first one represented by a chronic adaptation of
melanoma cells to extracellular acidosis, known to drive a particularly aggressive and vemurafenib-resistant
phenotype, the second one generated with chronic vemurafenib exposure. By performing in vitro tube formation assay and evaluating the expression levels of the VM markers EphA2 and VE-cadherin by Western blotting
and flow cytometer analyses, we demonstrated that vemurafenib-resistant cells obtained by both models are
characterized by an increased ability to perform VM. Moreover, by exploiting the CRISPR-Cas9 technique and
using the urokinase plasminogen activator receptor (uPAR) inhibitor M25, we identified uPAR as a driver of
VM expressed by vemurafenib-resistant melanoma cells. Thus, uPAR targeting may be successfully leveraged
as a new complementary therapy to inhibit VM in drug-resistant melanoma patients, to counteract the rapid
progression and dissemination of the disease. 相似文献
Journal of Neurology - MRI atrophy predicts cognitive status in AD. However, this relationship has not been investigated in early-onset AD (EOAD, < 65 years) patients... 相似文献
The hemodynamic response to mental challenge was studied in 40 male outpatients with mild essential hypertension. The patients were treated randomly either with a beta adrenoreceptor blocker (oxprenolol) or with a calcium entry blocker (nitrendipine). Cardiovascular reactivity was evaluated with two different mental arithmetic tasks before and six months after treatment by continuously measuring systolic and diastolic pressure (ultrasonic Doppler device), heart rate (electrocardiography), and stoke volume (impedance cardiography). Patients in both treatment groups had equal decreases in arterial pressure and the same pressures at rest. In patients receiving calcium entry blockers, mental challenge provoked an increase in stroke volume and a decrease in total peripheral resistance similar to results in the pretreatment phase. In contrast, beta adrenoreceptor blockade reversed the hemodynamic response pattern to a distinct decrease in stroke volume (p less than or equal to 0.05) and an increase in total peripheral resistance (p less than or equal to 0.05). In addition, an attenuated heart rate response (p less than or equal to 0.01) and a larger increase in diastolic pressure (p less than or equal to 0.01) were found in the beta blocker group compared with the calcium entry blocker group. Although beta blockers and calcium blockers produce equal decreases in arterial pressure, beta blockers evoke an abnormal hemodynamic response to mental challenge, whereas calcium entry blockers preserve the physiologic reactivity pattern of the untreated state. 相似文献
Background: The relationship between microbiology and histology in patients with ventilator-associated pneumonia has been sparsely described.
Methods: Twenty-five patients who died in the intensive care unit after their lungs had been mechanically ventilated for 72 h were studied. Twenty of the 25 died with clinical suspicion of pulmonary infection. A total of 375 immediate postmortem pulmonary biopsies were obtained after death and processed for quantitative microbiology and histology. Four evolutionary stages of pneumonia were defined: early, intermediate, advanced, and resolution.
Results: At least one specimen with histologic evidence of pneumonia was found in all but two patients (92%). Histologic pneumonia was a widespread and frequent process (46% of biopsies examined) involving predominantly the lower lobes (55% of all biopsies with pneumonia) and showing different histopathologic stages of progression coexisting in the same lung lobes. Lung cultures were frequently polymicrobial (149 of 375, 40% of the pulmonary biopsy cultures, and 20 of 25, 80% of the cases) and not always yielding the same pathogen (19 microorganisms) when comparing one lung to the other. Histopathology and microbiologic biopsy cultures showed a weak relationship (28% and 49% of species had counts greater or equal to 103 cfu/g in samples without pneumonia from patients with and without prior antibiotic treatment, respectively). Histopathologic evolutionary stages were not associated with any differences in quantitative culture results of pulmonary biopsies, independently of prior administration of antibiotics. Higher bacterial concentrations of biopsy cultures were associated with the absence of prior antibiotic treatment. 相似文献