Mycoplasma pneumoniae (MP) is, considered to affect rarely children less than 5 yrs of age. This study was performed to describe the epidemiology and the clinical features of MP lower respiratory tract infection (LRTI) in children, presenting to a tertiary children hospital. Eleven month-longitudinal study of LRTI due to MP, diagnosed by polymerase chain reaction (PCR) on throat swab specimen, was performed. Out of 866 children with LRTI admitted to the Gaslini Pediatric Institute in Genoa, 102 had a positive PCR for MP. We found 39 preschool-aged children, 42 school-aged children and 21 young adolescent [6.20 (3.81) yrs old]. Interestingly, eight MP+ infants had <8 months of age. The commonest presentations were cough and/or fever (76.5%). Tachypnoea, upper respiratory tract involvement, diarrhoea and vomiting were more common in the <5 yr Gr as compared to the other groups. Chest X-ray was found abnormal in 76 children: consolidations were the commonest finding. Laboratory test showed that the preschool-aged children had a higher number of lymphocytes (p<0.0001) and monocytes (p=0.009). Thrombocytosis was found in 35.7% of children and was more frequent in the preschool-aged children (p=0.013). MP infection is common in preschool-aged children, including young infants, and may have different clinical presentation, as compared to older children.
Human platelet-derived growth factor (PDGF) consists of two distinct but related polypeptide chains designated PDGF-A and PDGF-B. The gene encoding PDGF-B has given rise to the v-sis oncogene. In the present study the transforming activities of PDGF-A and PDGF-B genes are compared. The PDGF-A chain gene is markedly less efficient in inducing transformation than the PDGF-B gene under the influence of the same promoter. There are significant differences in the secretory and growth stimulating properties of the two chains. These properties appear to account for the much more potent transforming ability of the PDGF-B gene. These findings provide insights into biologic properties of a growth factor responsible for potent autocrine stimulation of abnormal cell proliferation.
Human keratinocytes isolated from a skin biopsy and cultured in vitro on a feeder-layer of irradiated fibroblasts reconstitute a stratified squamous epithelium suitable for grafting onto patients suffering from large burn wounds. Since conditioned medium from 3T3-J2 cells can partially substitute for the intact feeder-layer, we studied the possible involvement of insulin-like growth factors acting in a paracrine fashion. IGFs were measured (after Sephadex G-50 gel-chromatography in acid conditions) in media conditioned by a feeder-layer of lethally irradiated 3T3-J2 fibroblasts on which keratinocytes were grown. Immunoreactive (IR) IGF-I, IGF-II, and IGF binding activity were present in the medium conditioned by the feeder-layer. The medium conditioned by keratinocytes showed nearly undetectable amounts of IR IGF-I and IGF-II, suggesting that keratinocytes are unable to synthesize IGFs peptides. Recombinant IGF-I and IGF-II, and conditioned medium from 3T3-J2 cells, caused a dose-dependent increase of 3H-thymydine incorporation in cultured keratinocytes. The stimulatory effect of IGF and of 3T3-J2 conditioned medium was inhibited by the MoAb Sm 1.2, which recognizes both IGF-I and IGF-II but not insulin, and by the MoAb alpha IR-3, which is a specific antagonist of type-I IGF receptor. Fetal mouse-derived 3T3-J2 cells and adult human skin fibroblasts were equally able to sustain keratinocyte growth and in both cases addition of Sm 1.2 MoAb causes a 50% decrease in the keratinocyte number. When the non-IGF-producing BALB/c 3T3 cells were used as a feeder-layer, the keratinocytes number was similar to that observed with 3T3-J2 and with human fibroblasts plus the Sm 1.2 MoAb. IGF-I and IGF-II restored the BALB/c 3T3 growth promoting activity to the level of 3T3-J2 and of normal human fibroblasts. Our results suggest that fetal mouse 3T3-J2 and human fibroblasts synthesize IGF peptides, while keratinocytes do not. Fibroblast-derived IGFs stimulate keratinocyte growth in a paracrine fashion, suggesting their role in the regulation of keratinocyte proliferation in skin growth and in wound healing.
The c-fms protooncogene encodes the receptor for macrophage-colony-stimulating factor (CSF-1). Expression vectors containing either normal or oncogenic pointmutated human c-fins genes were transfected into interleukin 3 (IL-3)-dependent 32D cells in order to determine the effects of CSF-1 signaling in this murine clonal myeloid progenitor cell line. CSF-1 was shown to trigger proliferation in association with monocytic differentiation of the 32D-c-fins cells. Monocytic differentiation was reversible upon removal of CSF-1, implying that CSF-1 was required for maintenance of the monocyte phenotype but was not sufficient to induce an irrevocable commitment to differentiation. Human CSF-1 was also shown to be a potent chemoattractant for 32D-c-fms cells, suggesting that CSF-1 may serve to recruit monocytes from the circulation to tissue sites of inflammation or iu'ury. Although c-fms did not release 32D cells from factor dependence, pointmutated c-fms[S301,F969] (Leu-301 --Ser, Tyr-969 -* Phe) was able to abrogate their IL-3 requirement and induce tumorigenicity. IL-3-independent 32D-c-fms[S301,F969J cells also displayed a mature monocyte phenotype, implying that differentiation did not interfere with progression of these cells to the malignant state. All of these rmdings demonstrate that a single growth factor receptor can specifically couple with multiple intracellular signaling pathways and play a critical role in modulating cell proliferation, differentiation, and migration.
Aims The purpose is to find the gut microbial fingerprinting of pediatric patients with type 1 diabetes. Methods The microbiome of 31 children with type 1 diabetes at onset and of 25 healthy children was determined using multiple polymorphic region of the 16S rRNA. We performed machine learning analyses and metagenome functional analysis in order to identify significant taxa and their metabolic pathways content. Results Compared with healthy controls, patients showed a significantly higher relative abundance of the following most important taxa: B.stercoris, B.fragilis, B.intestinalis, B.bifidum, Gammaproteobacteria and its descendants, Holdemania, Synergistetes and its descendants. On the contrary the relative abundance of B.vulgatus, Deltaproteobacteria and its descendants, Parasutterella and the Lactobacillus, Turicibacter genera was significantly lower in patients with respects to healthy controls. The predicted metabolic pathway more associated with type 1 diabetes patients concerns "Carbon metabolism", sugar and iron metabolisms in particular. Among the clinical variables considered, BMI-SDS, anti insulin autoantibodies, glycemia, HbA1c, Tanner and age at onset emerged as the most significant positively or negatively correlated with specific clusters of taxa. Conclusions The relative abundance and the supervised analyses confirmed the importance of B. stercoris in type 1 diabetes patients at onset and showed a relevant role of Synergistetes and its descendants in patients with respect to healthy controls. In general the robustness and the coherence of the showed results underline the relevance of studying the microbioma using multiple polymorphic regions, different types of analysis and different approaches within each analysis.
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