Pathologie-biologie最新文献

Background

Somatic mutations in the calreticulin gene (CALR) were recently described in essential thrombocythemia (ET) and primary myelofibrosis with non-mutated JAK2 or MPL. The aim of this single-center study was to compare the clinical and biological features of ET patients according to their mutational status.

Methods

We included 40 patients with ET followed in hematology consultation. The JAK2 V617F mutation was assessed by quantitative PCR. For the detection of CALR mutations, we performed a PCR amplification of CALR exon 9 followed by direct sequencing.

Results

Among 40 study patients, 23 (57.5%) harbored V617F JAK2, 12 of the 17 patients without JAK2 mutation harbored CALR, no patient expressed MPL mutation and 5 were negative for all three mutations. Five types of mutations were identified with predominance of 52 bp deletion and 5 bp insertion (7/12 and 2/12 respectively). The incidence of thrombotic events at diagnosis was significantly higher in JAK2 mutated patients (P < 0.05). Biologically, patients with CALR mutation had significantly higher platelet count (P < 0.01) and significantly lower hemoglobin level (P < 0.05) than those with V617F JAK2 mutation.

Conclusion

JAK2 and CALR mutation screening in ET has a diagnostic value. Each mutation displays a distinct phenotype with uncertain impact on long-term outcome.

Fibrosis is characterized by disproportionate accumulation of collagens and other extracellular matrix substances, resulting in organ dysfunction and failure. In systemic sclerosis, cellular and molecular mechanisms involved in the pathophysiology of fibrosis are highly complex and yet barely understood. Anatomopathological findings showed the coexistence of patchy inflammatory cell infiltration, microvascular injuries, and fibrotic foci. One of the most commonly accepted hypotheses considers endothelial activation as the triggering phenomenon inducing inflammatory and autoimmunity activation. The resulting cytokines and autoantibodies production accelerates the proliferating rate of normal fibroblasts and their transformation into myofibroblasts, leading to diffuse fibrosis. This review aims to focus on cellular and molecular mechanisms implicated in the fibrogenesis of systemic sclerosis.

Aim

Oral mucositis is a very common complication of allograft. However, preventive treatments are still limited. The objective of this study is to identify risk factors for onset of oral mucositis in patients undergoing allogeneic hematopoietic stem cells transplantation (HSCT), to measure clinical consequences and to study their evolution according to type of prevention.

Patients and methods

All patients undergoing HSCT in hematology unit of CHU Besançon between January 2009 and August 2010 were included, and received according to their choice, either the standard protocol: solution of sodium bicarbonate 1.4% associated with chlorhexidine-chlorobutanol (Eludril^®) (n = 49), or the experimental treatment by the ionic solution, Caphosol^® (n = 42).

Results

The overall incidence of severe mucositis and mucositis is respectively 69% and 36%. In multivariate analysis, a myeloablative conditioning (OR = 11.1) and prevention of GVHD (graft-versus-host disease) including methotrexate (OR = 7.5) appear such as the two significant mucositis risk factors. The presence of mucositis resulting in a significant increase in the incidence of febrile aplasia (P = 0.008) and the use of opioid analgesics and parenteral nutrition (P < 10⁻³). The risk of acute gastrointestinal GVHD is also increased in severe mucositis (P = 0.01). The duration of post-transplant hospitalization is not changed. The type of prevention does not influence the incidence of mucositis (P = 0.11).

Conclusion

The consequences of mucositis are significant and the risk factors identified. The interest of the ionic solution Caphosol^® seems limited, the incidence of mucositis is not decreased by this prevention.

Background

Uveitis refers to intraocular inflammation. The pattern of uveitis is largely influenced by a multitude of factors including genetic background.

Aim

The purpose of our study was to identify the association between the polymorphism of the transmembrane region of MICA (MICA-TM) and uveitis in Tunisian patients with intraocular inflammation.

Patients and methods

A total of 79 Tunisian patients and 123 healthy controls were enrolled in our study. HLA-class I phenotyping was performed by microlymphocytotoxicity complement dependent and MICA-TM was genotyped by a semiautomatic fluorescent-labelled PCR method, amplicons were analysed on ABI Prism 310 genotyper. Comparisons of allele frequencies between patients and controls, and between patients’ subgroups were performed using SPSS 20.0.

Results

In our 79 patients, HLA-B27 showed a significant increased frequency when compared with healthy controls (P = 0.003, 7.88 [95% IC = 2.17–28.65]). The association was more significant when considering idiopathic anterior uveitis (P = 0.00002, OR = 11.65 [95% IC = 3.06–45.17]). No MICA allele was significantly increased in uveitis groups compared to controls. In the idiopathic uveitis group, MICA-A4 was associated with late age of onset of disease (P = 0.04). HLA-B51 and MICA-A6 were associated respectively with severe tyndall (P = 0.008) and with the presence of synechiae (P = 0.007).

Conclusion

Some clinical features of uveitis may be influenced by specific MICA-TM alleles. In our South Tunisian population, MICA plays a disease modifying role, rather than being an important gene in the susceptibility for developing of uveitis.

Background

The T1D is a multifactorial disease; with a strong genetic control. The human leukocyte antigen (HLA) system plays a crucial role in the autoimmune process leading to childhood diabetes. About 440,000 of the childhood population of the world (1.8 billion children under 14 years of age), have type 1 diabetes, and each year an additional 70,000 develop this disorder. The objective of this study was to investigate the distribution of HLA class II in Moroccan families of diabetic children to identify susceptibility alleles of the Moroccan population.

Subjects and methods

We included in this study, Moroccan families who have at least one child with T1D. The age of onset of diabetes was less than 15 years. HLA class II (DRB1* and DQB1*) was carried out by molecular biology techniques (PCR-SSP and PCR-SSO). The FBAT test (family-based association test) was used to highlight the association between T1D and the HLA-DRB1* and -DQB1* polymorphism.

Results

The association of HLA class II (DRB1*, DQB1*) in type 1 diabetes was analyzed in fifty-one Moroccan families, including 90 diabetics. The results revealed that the most susceptible haplotypes are the DRB1*03:01–DQB1*02:01, DRB1*04:05–DQB1*03:02 (Z = 3.674, P = 0.000239; Z = 2.828, P = 0.004678, respectively). And the most protective haplotype is the DRB1*15–DQB1*06.

Conclusion

This is the first family-based association study searching for an association between HLA class II and T1D in a Moroccan population. Despite the different ethnic groups forming Morocco, Moroccan diabetics share the most susceptible and protective HLA haplotypes with other Caucasians populations, specifically the European and Mediterranean populations.

The phosphoinositide-3 kinase (PI3K) - phosphoinositide-dependent protein kinase 1 (PDK1)-Akt/protein kinase B (PKB) cascade plays a critical role in cardiovascular development and tumor genesis. But the role of PDK1 in the microenvironment of heart and tumor remains unknown. To clarify the effects of PDK1 on tissue microenvironment in vivo, here, we created α-SMA-Cre-mediated excision of PDK1 mice. And the mice were injected subcutaneously with Lewis lung carcinoma (LLC) cells. We found PDK1-deficient mice had post-natal praecox dilated cardiomyopathy, decelerated tumor growth and severe tumor metastasis. Histopathological analysis revealed abnormality of vascular microenvironment in heart and primary tumor. In conclusion, PDK1 plays a pivotal role in regulating cardiac function and tumor metastasis by interfering with microenvironment.

Investigations of the etiologic agents of community-acquired acute respiratory illness may lead to better treatment decisions and patient outcomes. In a routine care setting, we assessed the diagnostic performance of a multiplex PCR assay with respect to conventional microbiological methods, in a continuous series of adult cases of community-acquired acute respiratory illness. We enrolled 279 adult patients hospitalised for community-acquired acute respiratory illness at Tours University Hospital during the winter of 2011–2012. Respiratory samples (mostly nasopharyngeal aspirates) were studied prospectively by indirect immunofluorescence assay and multiplex PCR, that enable detection of 8 viruses and 21 respiratory pathogens respectively. In total, 255 of the 279 (91.4%) samples had interpretable results by both methods. At least one respiratory pathogen was detected by multiplex PCR in 171 specimens (65%). Overall, 130 (76%) of the 171 positive samples were positive for only one respiratory pathogen, 37 (22%) samples were positive for two pathogens and four (2%) were positive for three pathogens. With indirect immunofluorescence assay, a respiratory virus was detected in 27 of the 255 (11%) specimens. Indirect immunofluorescence assay detected some of the influenza virus A (15/51, 29%) infections identified by multiplex PCR and some (7/15, 47%) human metapneumovirus and (5/12, 42%) respiratory syncytial virus infections, but it did not detect all the adenovirus infections. Thus, access to multiplex molecular assays improves the diagnostic spectrum and accuracy over conventional methods, increasing the frequency of identification of the respiratory pathogens involved in community-acquired acute respiratory illness.

Background

Behçet's disease is a multisystemic inflammatory disease characterized by recurrent oral and genital ulcers, skin lesions and uveitis. The diagnosis of Behçet's disease is based on clinical criteria. The etiology of the disease is unknown but the wide variations of ethnic prevalence and of the prevalence in the same ethnic group in different geographic areas indicate environmental triggering of a genetically determined disorder.

Patients and methods

A retrospective analysis of the medical charts of 150 Behçet's disease patients seen in our internal medicine department between 1995 and 2010 was undertaken. Patients with confirmed ocular involvement were analyzed and compared with those without ocular involvement.

Results

Among the 150 medical charts studied, 85 patients were included in the study. Thirty-three patients (38.5%) had ocular involvement. Mean age at ocular BD diagnosis onset were 35.3. Male to female ratio was 5.6. Ocular involvement was bilateral in 26 patients (78.8%). Uveitis was the most common ocular lesion (n = 31 patients, 93.9%). Panuveitis was the most common anatomical location (n = 21, 63.6%). The comparison of patients treated for BD with or without ocular involvement showed a statistically significant association between ocular and neurological manifestations (p = 0.03). All patients with ocular involvement were treated with corticosteroids. Immunosuppressive (IS) treatments were used in 28 patients (84.8%). Cyclophosphamide was the most used as first-line treatment (71.4%). Cyclophosphamide relayed by azathioprine was the most adopted protocol (28.5%). In case of resistance or relapse and depending on the other manifestations of the BD, the IS used in first intention was replaced by another one. Seven of the 33 patients had received treatment with infliximab (IFX) after failure of other therapeutic lines.

Conclusion

Ocular prognosis in the BD can be improved by early treatment and regular monitoring. It is important to adjust the therapeutic protocol to the anatomic form, to the severity of uveitis and to the extra-ocular manifestations associated.

Diabetes is recognized as a major public health problem responsible for early morbidity and mortality with a worldwide prevalence in permanent increase. The type II diabetes once called non-insulin dependent diabetes, accounts for about 90 % of all forms of diabetes and is characterized by abnormalities that affect insulin secretion and insulin action and thus, induces hyperglycemia. The aim of this work is to study the involvement of a key enzyme of glycolysis, glyceraldehyde-3-phosphate dehydrogenase in type 2 diabetes. This work includes a biochemical, kinetic studies, and the study of the expression of GAPDH in subjects with type 2 diabetes. From our study, we could classify the diabetic subjects into two categories: the first one, consisting of subjects in whom GAPDH has a specific activity and an electrophoretic profile similar to healthy subjects, and the second one, in which there is an inhibition of GAPDH. Our results suggest that, in 60 % of our patients with type 2 diabetes, a reversible inhibition of GAPDH is observed. This inhibition is probably mediated by the ionic interaction with the erythrocyte membrane protein, band 3.