Transmission of schistosomiasis in an urban population and prevalence of intestinal helminthiasis in Bamako, Mali

Parasitological, malacological and anthropological studies were performed to assess the prevalence of Schistosoma haematobium and S. mansoni in schoolchildren living in the suburban area of Bamako. A total of 1017 schoolchildren aged 6-14 years were selected in two different areas between September 1997 and December 1999. In Djikoroni, the prevalence of S. haematobium and S. mansoni was 80.7% (339/420) and 22.8% (85/372) respectively. There was no significant difference of prevalence and intensity of infection with S. haematobium between schools, gender and age (p > 0.05), whereas, those of S. mansoni were higher in the vicinity of (+/- 100 m from) major sites where infected Biomphalaria pfeifferi were found (p < 0.001). In Niomirambougou, S. haematobium was prevalent in 46.7% (279/597) and S. mansoni in 28.2% (134/475). Boys and children aged 11-14 years were more infected (p < 0.001). Associated intestinal helminths (Hymenolepis nana, Necator americanus and Ascaris lumbricoides) were relatively scarce (prevalence < 1%). The prevalences of schistosome infected snails intermediate host were relatively high, 49.3% (100/203) in B. pfeifferi, 20.6% (88/138) in B. truncatus and 24.1% (7/29) in B. globosus. We recorded a total of 2514 water contacts about which 1130 in December and 1384 in January. Most of the children, 42.9% (1077/2511) were attracted to water bodies for bathing, swimming and playing, suggesting the lack of recreational facilities in these areas. Developing local control programmes in schools located in the vicinity of water bodies would contribute to break the parasite transmission cycle in Bamako.     

Preoperative diagnosis of clear cell sarcoma of the kidney by detection of BCOR internal tandem duplication in circulating tumor DNA

Clear cell sarcoma of the kidney (CCSK) is the second most common renal malignancy in children. The prognosis is poorer in CCSK than in Wilms’ tumor, and multimodal treatment including surgery, intensive chemotherapy, and radiation is required to improve the outcome for children with CCSK. Histological evaluation is required for the diagnosis. However, biopsies of tumors to obtain diagnostic specimens are not routinely performed because of the risk of spreading tumor cells during the procedure. Recently, internal tandem duplication (ITD) of BCOR has been recognized as a genetic hallmark of CCSK. We herein established a novel BCOR‐ITD‐specific polymerase chain reaction method with well‐designed primers, and then performed a liquid biopsy for cell‐free DNA (cfDNA) obtained from plasma of three children with nonmetastatic renal tumors (stage II) and from one control. BCOR‐ITD was positively detected in the cfDNA of two cases, both of which were later diagnosed as CCSK based on histological feature of the resected tumor specimen, while it was not detected for a normal control and a patient diagnosed with Wilms’ tumor. Our study is the first one of preoperative circulating tumor DNA assay in pediatric renal tumors. The liquid biopsy method enables less invasive, preoperative diagnosis of CCSK with no risk of tumor spillage, which can avoid iatrogenic upstaging.     

Fate of Worn‐Out Functional Teeth in the Upper Jaw Dentition of Sicyopterus japonicus (Gobioidei: Sicydiinae) During Tooth Replacement

Mochizuki and Fukui (Jpn J Ichthyol 30 ( 1983 ) 27–36) studied the development and replacement of the upper jaw teeth in a Japanese fish species, Sicyopterus japonicus (Gobioidei: Sicydiinae), and they reported that worn‐out functional teeth in the upper jaw were not shed outside the skin but were taken into the soft tissue of the upper jaw and completely resorbed there. To date, however, this phenomenon appears poorly documented. Furthermore, the mechanism for the resorption of these teeth remains to be determined. In this study, we examined this phenomenon by using 3D microcomputed tomography (m‐CT), scanning electron microscopy (SEM), and various techniques of light (LM) and electron (EM) microcopy. This study demonstrated that the upper jaw dentition of this fish was more or less simultaneously replaced with the replacement occurring during short time periods and that the lingual movement of the replacement teeth to the functional tooth position advanced simultaneously in a given row. Furthermore, our study also revealed that many worn‐out functional teeth were engulfed by the oral epithelium, invaginated into the lingual shallow ditch of the premaxilla, and were resorbed/degraded completely by numerous foreign body giant cells rather than by odontoclasts during periods of at least three intervals of tooth replacement. The complete resorption/degradation of worn‐out functional teeth in the soft tissue of the upper jaw suggests the possibility of the reuse of their components (minerals such as Ca and P, including Fe) for rapid and successional production of new replacement teeth in the upper jaw of adult S. japonicus. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:111–124, 2018. © 2017 Wiley Periodicals, Inc.     

CD83+CCR7− Dendritic Cells Accumulate in the Subepithelial Dome and Internalize Translocated Escherichia coli HB101 in the Peyer’s Patches of Ileal Crohn’s Disease

Recurrent Crohn’s disease originates with small erosions in the follicle-associated epithelium overlying the Peyer’s patches. Animal studies have illustrated mucosal immune regulation by dendritic cells located in the subepithelial dome. The aim of this study was to characterize the dendritic cells at this specific site in patients with Crohn’s disease. Ileal tissues were obtained after surgery performed on Crohn’s patients; ileal samples from noninflammatory bowel disease and ulcerative colitis served as standard and inflammatory controls, respectively. Flow cytometry of isolated intestinal mononuclear cells showed a larger subset of dendritic cells in Crohn’s samples compared with controls. This finding was corroborated by confocal microscopy, showing enhanced infiltrates of cells positive for the dendritic cell markers, DC-SIGN⁺ and CD83⁺, in the subepithelial dome. Moreover, the CD83⁺ cells in Crohn’s tissues showed reduced expression of the lymph node migratory receptor, CCR7, possibly contributing to the high numbers of dendritic cells. After exposure to nonpathogenic Escherichia coli in Ussing chambers, dendritic cells in the subepithelial dome of Crohn’s disease demonstrated increased co-localization with translocated bacteria. Immunohistochemical results revealed that DC-SIGN⁺ cells in Crohn’s tissues were found to express toll-like receptor 4 and produce tumor necrosis factor-α. In conclusion, nonmigrating dendritic cells that accumulate in the subepithelial dome and internalize nonpathogenic bacteria may be important for the onset and perpetuation of mucosal inflammation in Crohn’s disease.     

Coupled 182W-142Nd constraint for early Earth differentiation

Recent high precision ¹⁴²Nd isotope measurements showed that global silicate differentiation may have occurred as early as 30–75 Myr after the Solar System formation [Bennett V, et al. (2007) Science 318:1907–1910]. This time scale is almost contemporaneous with Earth’s core formation at ∼30 Myr [Yin Q, et al. (2002) Nature 418:949–952]. The ¹⁸²Hf-¹⁸²W system provides a powerful complement to the ¹⁴²Nd results for early silicate differentiation, because both core formation and silicate differentiation fractionate Hf from W. Here we show that eleven terrestrial samples from diverse tectonic settings, including five early Archean samples from Isua, Greenland, of which three have been previously shown with ¹⁴²Nd anomalies, all have a homogeneous W isotopic composition, which is ∼2ε-unit more radiogenic than the chondritic value. By using a 3-stage model calculation that describes the isotopic evolution in chondritic reservoir and core segregation, as well as silicate differentiation, we show that the W isotopic composition of terrestrial samples provides the most stringent time constraint for early core formation (27.5–38 Myr) followed by early terrestrial silicate differentiation (38–75 Myr) that is consistent with the terrestrial ¹⁴²Nd anomalies.     

Hypoxia augments MHC class I antigen presentation via facilitation of ERO1‐α‐mediated oxidative folding in murine tumor cells

To establish an effective cancer immunotherapy, it is crucial that cancer cells present a cancer‐specific antigen in a hypoxic area, a hallmark of the tumor microenvironment. Here, we show the impact of hypoxia on MHC class I antigen presentation in vitro and in vivo in murine tumors. Activation of antigen‐specific CTLs by tumor cells that had been pre‐incubated under a condition of hypoxia was enhanced compared with that by tumor cells pre‐incubated under a condition of normoxia. Cell surface expression of MHC class I‐peptide complex on the tumor cells was increased under a condition of hypoxia, thereby leading to higher susceptibility to specific CTLs. We show that the hypoxia‐inducible ER‐resident oxidase ERO1‐α plays an important role in the hypoxia‐induced augmentation of MHC class I‐peptide complex expression. ERO1‐α facilitated oxidative folding of MHC class I heavy chains, thereby resulting in the augmentation of cell surface expression of MHC class I‐peptide complex under hypoxic conditions. These results suggest that since the expression of MHC class I‐peptide complex is augmented in a hypoxic tumor microenvironment, strategies for inhibiting the function of regulatory T cells and myeloid‐derived suppressor cells and/or immunotherapy with immune checkpoint inhibitors are promising for improving cancer immunotherapy.     

Intrapulmonary lymph nodes: thin-section CT findings, pathological findings, and CT differential diagnosis from pulmonary metastatic nodules

We compared the thin-section CT findings of 11 intrapulmonary lymph nodes with pathological findings and evaluated the possibility of CT scan differential diagnosis from pulmonary metastatic nodules. First, we retrospectively reviewed CT scan and pathological findings of intrapulmonary lymph nodes. The median size of these nodules was 6.2 mm. The nodules appeared round (n=3) or angular (n=8) in shape with a sharp border, and they were found below the level of the carina. The median distance from the nearest pleural surface was 4.6 mm, and 3 of the 11 nodules were attached to the pleura. On thin-section CT scan, linear densities extending from the intrapulmonary lymph nodes were frequently visualized, and were pathologically proven to be ectatic lymphoid channels. We then compared the thin-section CT findings of 8 metastatic nodules less than 1 cm in diameter with those of the 11 intrapulmonary lymph nodes. The median size of these nodules was 6.8 mm, and the median distance from the nearest pleural surface was 16 mm. All nodules appeared round in shape. None of the nodules had linear densities extending from the nodules. The linear densities on thin-section CT scan may be the most useful characteristic of intrapulmonary lymph nodes, when differential diagnosis from metastatic nodules is necessary.     

ASRI2005-88 Comparable levels of CD4+CD25+ CTLA4+ Treg cells in peripheral blood of pre-eclampsia and normal pregnant patients

The acceptance of the semiallogeneic fetus within the maternal environment requires tolerance mechanisms not fully characterized yet. Normal pregnancy is known to be associated with a Th2 profile. Furthermore, T-regulatory cells were proposed to regulate the Th2/Th1 balance at early stages of pregnancy. Treg may avoid the shift to a Th1 profile preventing miscarriage. Accordingly, spontaneous abortion is characterized by a Th1 dominance and diminished levels of Tregulatory cells (Treg). The major aim of the present work was to investigate if pre-eclampsia, a late immunological complication of pregnancy, is characterized by similar hallmarks. Therefore, we measured the surface antigens CD4, CD25, CD8, CTLA4 (as well as the secretion of IL-10) in peripheral blood from patients suffering from pre-eclampsia (n = 8) and age-matched patients undergoing normal pregnancies (n = 9) by 4-colour flow-cytometry. We were not able to find any significant differences in the levels of CD4⁺, CD25⁺, CD8⁺, CTLA4, CD4⁺/CD25⁺, CD4⁺/CD25^bright, CD4⁺/CTLA4, CD25⁺/CTLA4, CD4⁺/CD25⁺/CTLA4, CD8⁺/CD25⁺, CD8⁺/CTLA4 or CD8⁺/CD25⁺/CTLA4 cell subsets. Our data suggest that Treg may not participate in the onset of pre-eclampsia and suggest other regulatory mechanisms during late pregnancy.     

Autosomal glycogenosis of liver and muscle due to phosphorylase kinase deficiency is caused by mutations in the phosphorylase kinase beta subunit (PHKB)

Glycogen storage disease due to phosphorylase kinase deficiency occurs in several variants that differ in mode of inheritance and tissue- specificity. This heterogeneity is suspected to be largely due to mutations affecting different subunits and isoforms of phosphorylase kinase. The gene of the ubiquitously expressed beta subunit, PHKB, was a candidate for involvement in autosomally transmitted phosphorylase kinase deficiency of liver and muscle. To identify such mutations, the complete PHKB coding sequence was amplified by RT-PCR of RNA isolated from blood samples of patients and analyzed by direct sequencing of PCR products. The characterization of mutations was complemented by PCR of genomic DNA. In one female and four male patients, we identified five independent nonsense mutations (Y418ter; R428ter; Y974H+E975ter; Q656ter in two cases), one single-base insertion in codon N421, one splice-site mutation affecting exon 31, and a large deletion involving the loss of exon 8. Although these severe translation-disrupting mutations occur in constitutively expressed sequences of the only known beta subunit gene of phosphorylase kinase, PHKB, they are associated with a surprisingly mild clinical phenotype, affecting virtually only the liver, and relatively high residual enzyme activity of approximately 10%.