Diffuse large B cell lymphoma presenting as Horner's syndrome in a patient diagnosed with neurofibromatosis type 1: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Horner's syndrome has a variety of etiologies ranging from benign to serious life-threatening conditions and has been infrequently reported as a presenting symptom of patients with lymphoid neoplasms. Only one case of Burkitt's lymphoma presenting with toothache, paresthesia, and Horner's syndrome has been described and no case reports of diffuse large B-cell lymphoma as the etiology of Horner's syndrome currently exist in the literature. In addition, lymphoid neoplasms have rarely been reported to occur in patients with neurofibromatosis type 1 despite an increased risk of many types of cancer in such cases.</p> <p>Case presentation</p> <p>A 28-year-old Thai man presented with a progressively enlarged left supraclavicular mass together with a significant weight loss and night sweating for four months. He also noticed hoarseness and ptosis of his left eye associated with double vision for two months. Physical examination revealed large supraclavicular lymphadenopathy and Horner's syndrome (ptosis, miosis, and anhydrosis) on the left side of his face. A large mediastinal mass was clearly detected by chest X-ray and computed tomography and subsequent lymph node biopsy provided a diagnosis of diffuse large B-cell lymphoma. Interestingly, the patient was also definitely diagnosed with neurofibromatosis type 1 from multiple café au lait macules, axillary freckles, three neurofibromas, multiple Lisch nodules, and a history of affected family members. He subsequently received chemotherapy with a good response. Twenty-seven cases of various types of lymphoid neoplasms previously reported to occur in neurofibromatosis type 1 patients were also extracted from the literature. All cases were non-Hodgkin lymphoma and the major subtype was T-cell. Only nine cases were B-cell lymphoma. The majority of cases were young with a median age at lymphoma diagnosis of 9.4 years (range 1.1 to 77 years). Two-thirds of the cases were boys or men. Other concomitant malignancies were brain tumor, colorectal cancer, pheochromocytoma, and acute lymphoblastic leukemia.</p> <p>Conclusions</p> <p>We describe for the first time a case of diffuse large B-cell lymphoma that occurred in a neurofibromatosis type 1 patient with Horner's syndrome. Horner's syndrome can be an initial manifestation of diffuse large B-cell lymphoma. Patients who present with a classical triad of Horner's syndrome should always be fully investigated for lymphomatous involvement, especially in the thorax. The exact molecular mechanism for diffuse large B-cell lymphoma development in neurofibromatosis type 1 cases remains to be elucidated.</p

DNA Methylation in hypoxia in Mycobacterium tuberculosis

Tuberculosis is one of the most lethal contagious diseases caused by Mycobacterium tuberculosis (MTB), in many cases, the infected did not show any symptoms, because the bacilli entered the dormant stage in granulomas. The dormant stage of MTB is also associated with higher resistance to drugs and the immune system. Among multiple epigenetic regulations critical to MTB stress responses, DNA methylation is necessary for the survival of MTB in hypoxic conditions, which is a common stress event during granuloma formation. This review gathers previous findings and demonstrates a meta-analysis by collecting hypoxia gene expression data from several articles and perform association analysis between those genes and methylation site profiles across whole genomes of representative strains pf lineage 2 and 4. While more data is required for more conclusive support, our results suggest that methylation sites in the possible promoter regions may induce differential gene regulation in hypoxia.Comment: 20 pages, 9 table

Molecular alterations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) metabolic genes and additional genetic mutations in newly diagnosed acute myeloid leukemia patients

<p>Abstract</p> <p>Background</p> <p>Isocitrate dehydrogenase 1 and 2 (<it>IDH1 </it>and <it>IDH2</it>) metabolic genes encode cytosolic and mitochondrial enzymes that catalyze the conversion of isocitrate to α-ketoglutarate. Acquired somatic mutations of <it>IDH1 </it>and <it>IDH2 </it>have recently been reported in some types of brain tumors and a small proportion of acute myeloid leukemia (AML) cases.</p> <p>Methods</p> <p>Two-hundred and thirty newly diagnosed AML patients were analyzed for the presence of <it>IDH1 </it>and <it>IDH2 </it>heterozygous mutations by polymerase chain reaction-denaturing high performance liquid chromatography (PCR-DHPLC) followed by direct sequencing. Clinical and biological characteristics were analyzed and correlated to the <it>IDH </it>mutational status. Coexisting mutations such as <it>FLT3</it>, <it>PML-</it>RARA, <it>RAS</it>, <it>AML1</it>, and <it>NPM1 </it>mutations were additionally explored.</p> <p>Results</p> <p>The prevalence of <it>IDH1 </it>and <it>IDH2 </it>mutations was 8.7% (20/230) and 10.4% (24/230), respectively. Six missense mutations were identified among <it>IDH1</it>-mutated cases; p.R132H (n = 8), p.R132C (n = 6), p.R132S (n = 2), p.R132G (n = 2), p.R132L (n = 1), and p.I99M (n = 1). Two missense mutations were found in <it>IDH2</it>-mutated cases; p.R140Q (n = 20) and p.R172K (n = 4). No patients had dual <it>IDH1 </it>and <it>IDH2 </it>mutations. About 18% of AML with normal cytogenetics and 31% of acute promyelocytic leukemia had <it>IDH </it>mutations. Half of the <it>IDH</it>-mutated cohort had normal karyotype and the major FAB subtype was AML-M2. Interestingly, <it>IDH1</it>- and <it>IDH2</it>-mutated cases predominantly had <it>NPM1 </it>mutations (60-74%) as compared to the wild type (P < 0.001). Very few <it>IDH</it>-mutated cases had <it>FLT3 </it>and/or <it>RAS </it>abnormalities and none of them had <it>AML1 </it>mutations. Older age and higher median platelet counts were significantly associated with <it>IDH2 </it>mutations although the clinical impact of either <it>IDH1 </it>or <it>IDH2 </it>mutations on patients' overall survival could not be observed.</p> <p>Conclusion</p> <p>Overall, 19% of newly diagnosed AML patients had alterations of <it>IDH </it>genes. No patients concurrently carried both <it>IDH1 </it>and <it>IDH2 </it>mutations suggesting that these mutations were mutually exclusive. <it>NPM1 </it>mutation appears as a major coexisting genetic mutation in <it>IDH</it>-mutated patients. Our present data failed to support the prognostic relevance of <it>IDH </it>mutations although alterations of these metabolic genes potentially have an important role in leukemia development.</p

Sharing H5N1 Viruses to Stop a Global Influenza Pandemic

Indonesia's refusal to share samples of H5N1 virus with World Health Organization for most of 2007 is distressing and potentially dangerous for global public health, argue the authors

Enhanced Susceptibility of Nasal Polyp Tissues to Avian and Human Influenza Viruses

BACKGROUND: Influenza viruses bind and infect respiratory epithelial cells through sialic acid on cell surface. Differential preference to sialic acid types contributes to host- and tissue-tropism of avian and seasonal influenza viruses. Although the highly pathogenic avian influenza virus H5N1 can infect and cause severe diseases in humans, it is not efficient in infecting human upper respiratory tract. This is because of the scarcity of its receptor, α2,3-linked sialic acid, in human upper airway. Expression of sialic acid can be influenced by various factors including inflammatory process. Allergic rhinitis and nasal polyp are common inflammatory conditions of nasal mucosa and may affect expression of the sialic acid and susceptibility to influenza infection. METHODOLOGY/PRINCIPAL FINDING: To test this hypothesis, we detected α2,3- and α2,6-linked sialic acid in human nasal polyp and normal nasal mucosal tissues by lectin staining and infected explants of those tissues with avian influenza viruses H5N1 and seasonal influenza viruses. We show here that mucosal surface of nasal polyp expressed higher level of α2,3- and α2,6-linked sialic acid than normal nasal mucosa. Accordingly, both H5N1 avian influenza viruses and seasonal influenza viruses replicated more efficiently in nasal polyp tissues explants. CONCLUSIONS/SIGNIFICANCE: Our data suggest a role of nasal inflammatory conditions in susceptibility to influenza infection, especially by avian influenza viruses, which is generally inefficient in infecting human upper airway. The increased receptor expression may contribute to increased susceptibility in some individuals. This may contribute to the gradual adaptation of the virus to human population

Contact Mixing Patterns and Population Movement among Migrant Workers in an Urban Setting in Thailand.

Data relating to contact mixing patterns among humans are essential for the accurate modeling of infectious disease transmission dynamics. Here, we describe contact mixing patterns among migrant workers in urban settings in Thailand, based on a survey of 369 migrant workers of three nationalities. Respondents recorded their demographic data, including age, sex, nationality, workplace, income, and education. Each respondent chose a single day to record their contacts; this resulted in a total of more than 8300 contacts. The characteristics of contacts were recorded, including their age, sex, nationality, location of contact, and occurrence of physical contact. More than 75% of all contacts occurred among migrants aged 15 to 39 years. The contacts were highly clustered in this age group among migrant workers of all three nationalities. There were far fewer contacts between migrant workers with younger and older age groups. The pattern varied slightly among different nationalities, which was mostly dependent upon the types of jobs taken. Half of migrant workers always returned to their home country at most once a year and on a seasonal basis. The present study has helped us gain a better understanding of contact mixing patterns among migrant workers in urban settings. This information is useful both when simulating disease epidemics and for guiding optimal disease control strategies among this vulnerable section of the population

Cultural Practices Shaping Zoonotic Diseases Surveillance: The Case of Highly Pathogenic Avian Influenza and Thailand Native Chicken Farmers

Effectiveness of current passive zoonotic disease surveillance systems is limited by the under-reporting of disease outbreaks in the domestic animal population. Evaluating the acceptability of passive surveillance and its economic, social and cultural determinants appears a critical step for improving it. A participatory rural appraisal was implemented in a rural subdistrict of Thailand. Focus group interviews were used to identify sanitary risks perceived by native chicken farmers and describe the structure of their value chain. Qualitative individual interviews with a large diversity of actors enabled to identify perceived costs and benefits associated with the reporting of HPAI suspicions to sanitary authorities. Besides, flows of information on HPAI suspected cases were assessed using network analysis, based on data collected through individual questionnaires. Results show that the presence of cockfighting activities in the area negatively affected the willingness of all chicken farmers and other actors to report suspected HPAI cases. The high financial and affective value of fighting cocks contradicted the HPAI control policy based on mass culling. However, the importance of product quality in the native chicken meat value chain and the free veterinary services and products delivered by veterinary officers had a positive impact on suspected case reporting. Besides, cockfighting practitioners had a significantly higher centrality than other actors in the information network and they facilitated the spatial diffusion of information. Social ties built in cockfighting activities and the shared purpose of protecting valuable cocks were at the basis of the diffusion of information and the informal collective management of diseases. Building bridges with this informal network would greatly improve the effectiveness of passive surveillance

AML1 mutation and its coexistence with different transcription factor gene families in de novo acute myeloid leukemia: redundancy or synergism

AML1 mutations were identified in 6.3% of AML patients with chromosomal translocations involving CBF, PML-RARα, HOX, or ETS transcription factor (TF) gene families. Rare chromosomal abnormalities, t(16;21) and t(7;11), were also found. This study represents the first series to demonstrate the coexistence of known and novel AML1 mutations with different TF gene mutations. Although the occurrence of two TF gene mutations may appear unnecessary, the possible synergistic mechanism between different TF gene families cannot be excluded and needs to be further explored