HUMAN NEUROBLASTOMA CELL TRANSDIFFERENTIATION: BIOCHEMICAL CHARACTERISTICS OF CLONED CELL VARIANTS

Neuroblastomas are tumors of neural crest origin which histologically may exhibit multiple cellular phenotypes. Many neuroblastoma cell lines comprise morphologically distinct but karyotypically identical types of cells. One cell type (N) is neuroblastic and poorly substrate-attached whereas the other cell type (S) is large, flat and strongly adherent. N and S cells can undergo bidirectional, morphological interconversion. Biochemical studies have shown that N-type cells from the cell line SK-N-SH express activities for neurotransmitter enzymes whereas S counterparts do not. By contrast, the S cells express tyrosinase, a melanocyte marker. This morphological and biochemical interconversion between two phenotypes is termed transdifferentiation. A third cell type observed in several neuroblastoma cell lines has a morphology intermediate between that of the N and S cells and is termed I. To further characterize these three cell types, N, S and I cells from six human neuroblastoma cell lines were analyzed for expression of phenotypic marker enzymes, intermediate filament proteins, fibronectin, EGF receptor and N-myc. N cells have properties of neuroblastic cells, as indicated by their morphology, neurotransmitter-synthesizing enzyme activity, norepinephrine uptake, and expression of neurofilament proteins. S cells may represent one or more non-neuronal neural crest derivatives, e.g., Schwann cells, melanocytes, or mesectodermal cells, as indicated by their lack of neurotransmitter enzymes, and their expression of vimentin, fibronectin, and tyrosinase activity. I cells express both vimentin and neurofilament proteins and thus share properties of both N and S cells. I cells may be pluripotent stem cells capable of differentiating either into neuroblasts or other neural crest derivatives. Alternatively, the I cells may represent a transitional form in the N and S transdifferentiation process. N and S cells may be regulated by different control mechanisms as indicated by their differential expression of EGF receptor and by possible differences in N-myc expression. Several conclusions can be drawn. First, the occurrence of N, S and I cell types is prevalent among neuroblastoma cell lines. Second, human neuroblastoma cells may undergo transdifferentiation between two neuroectodermal differentiation programs. This phenotypic interconversion in culture may reflect the cellular heterogeneity observed in neuroblastoma tumors. The capacity of human neuroblastoma cells to undergo phenotypic interconversion in culture may be closely linked to the ability of some tumors to undergo differentiation and spontaneous regression in the patient

Preventing the spread of Coronavirus in ENT unit, our experience

SARS-CoV19 is spreading all over the world starting from China in the end of 2019. This important emergency involved every single aspect of ordinary life. Even hospitals have undergone changes with the aim of ensuring the best care and preventing the spread of the virus. This is a personal contribution to illustrate all the measures put in place to avoid contagion. Although in an ENT unit you have strictly to do with the airway, none of the staff so far has been positive. Keyword: SARS-CoV19, safety, prevention, ENT, contagion

Pituary autoimmunity in patients with diabetes mellitus and other endocrine disorders

Objective: Pituitary autoimmunity is often found in association with other endocrine autoimmune or non-autoimmune diseases. Aim of the study was to assess the prevalence of serum pituitary antibodies (PitAb) in patients with Type 1 diabetes mellitus (T1DM) or Type 2 diabetes mellitus (T2DM). Research design and methods: In this casecontrol study 111 patients with T1DM, 110 patients with T2DM, and 214 healthy controls were enrolled in a tertiary referral center. Pituitary, thyroperoxidase, thyroglobulin, 21-hydroxylase, and parietal cell antibodies were assessed in all cases. Endocrine function was further assessed by basal hormone measurement and by dynamic tests, as well as a pituitary magnetic resonance imaging (MRI) was performed in those patients found positive for PitAb. Results: PitAb prevalence was higher in T1DM (4 out of 111, 3.6%) than in T2DM (0 out of 110, p=0.045) and in healthy subjects (1 out of 214, 0.5% p=0.029). Prevalence of other autoimmune diseases was significantly higher in patients with T1DM (45 out of 111, 40.5%) when compared with patients with T2DM (18 out of 110 T2DM, 16.3%, p<0.001). Patients with T1DM and PitAb positivity were found with a pituitary lesion at MRI in 2 cases and pituitary dysfunction in one case. Conclusions: A significant association between pituitary autoimmunity and T1DM was found, in particular in subjects with one or more other endocrine autoimmune diseases

Use of Nutraceuticals in Elderly to Fight Inflammation and Immuno-Senescence: A Randomized Case-Control Study

Elderly people are at high risk of suffering from infection and being affected by severe forms of disease because their immunosystem suffers from aging. The alteration of normal immune functions causes the increase of pro-inflammatory cytokines which can expose these people to increased risk of developing pathologies as cancer, diabetes, and/or arthritis. Some supplements could be helpful for restoring normal immune functions. We conducted a case-control study to evaluate the efficacy of a supplement containing Sambucus nigra, zinc, tyndallized Lactobacillus acidophilus (HA122), arabinogalactans, vitamin D, vitamin E, and vitamin C to improve the inflammatory levels (IL-6 and CRP) and to modulate the lymphocytes growth. Additionally, we analyzed wellness by self-questionnaire. This study had two control group: a young group and an elderly one. Our study showed that treating elderly patients with the supplement for 30 days improved IL-6, CRP, and lymphocytes levels; the result was independent from the dosage of the supplements used. Elderly patients, despite the improvement, were not able to reach the same conditions of young patients; however, most of the patients (&gt;70%) claimed to &ldquo;feel better&rdquo; after the use of the supplement. The use of this supplement should be considered at a low dosage for a prolonged period to reduce inflammation and modulate immune senescence in patients over 60 years old

Nutritional Factors Modulating Alu Methylation in an Italian Sample from The Mark-Age Study Including Offspring of Healthy Nonagenarians.

Alu hypomethylation promotes genomic instability and is associated with aging and age-related diseases. Dietary factors affect global DNA methylation, leading to changes in genomic stability and gene expression with an impact on longevity and the risk of disease. This preliminary study aims to investigate the relationship between nutritional factors, such as circulating trace elements, lipids and antioxidants, and Alu methylation in elderly subjects and offspring of healthy nonagenarians. Alu DNA methylation was analyzed in sixty RASIG (randomly recruited age-stratified individuals from the general population) and thirty-two GO (GeHA offspring) enrolled in Italy in the framework of the MARK-AGE project. Factor analysis revealed a different clustering between Alu CpG1 and the other CpG sites. RASIG over 65 years showed lower Alu CpG1 methylation than those of GO subjects in the same age class. Moreover, Alu CpG1 methylation was associated with fruit and whole-grain bread consumption, LDL2-Cholesterol and plasma copper. The preserved Alu methylation status in GO, suggests Alu epigenetic changes as a potential marker of aging. Our preliminary investigation shows that Alu methylation may be affected by food rich in fibers and antioxidants, or circulating LDL subfractions and plasma copper