Carboniferous of Eastern Kentucky - Stops 4-6.

This guidebook was produced for participants of the Sixth Gondwana Symposium held at the Institute of Polar Studies in August 1985. The trip traverses the highly scenic Appalachian Plateau. Enroute to eastern Kentucky, nonmarine sandstone, mudstone, coal, and limestone of the Upper Carboniferous to Permian (?) Dunkard Group, and Upper Carboniferous Monongahela and Conemaugh Formations will be examined in southern Ohio and western West Virginia. In eastern Kentucky, examination of the rocks will proceed up through the sequence starting with the Lower Carboniferous Berea Sandstone, a shallow marine deposit with abundant sedimentary structures; followed by the Borden Formation, which represents a prograding delta with shelf to basin facies including turbidites and abundant sedimentary structures; followed by the Borden Formation, which represents a prograding delta with shelf to basin facies including turbidites and abundant sedimentary structures, trace, and invertebrate fossils; the Slade Formation, a shallow carbonate sequence with paleokarst and paleosol features, and ending with the Upper Carboniferous Breathitt Formation, a marine to nonmarine sandstone, mudstone, and coal unit with famous coal ball localities

Nilotinib and Imatinib Are Comparably Effective in Reducing Growth of Human Eosinophil Leukemia Cells in a Newly Established Xenograft Model

We developed a xenograft model of human Chronic Eosinophilic Leukemia (CEL) to study disease progression and remission-induction under therapy with tyrosine kinase inhibitors using imatinib and nilotinib as examples. The FIP1L1/PDGFRA+ human CEL cell lineEOL-1 was injected intravenously into scid mice, and MR imaging and FACS analysis of mouse blood samples were performed to monitor disease development and the effects of imatinib and nilotinib. Organ infiltration was analyzed in detail by immunohistochemistry after sacrifice. All animals developed CEL and within one week of therapy, complete remissions were seen with both imatinib and nilotinib, resulting in reduced total tumor volumes by MR-imaging and almost complete disappearance of EOL-1 cells in the peripheral blood and in tissues. The new model system is feasible for the evaluation of new tyrosine kinase inhibitors and our data suggest that nilotinib may be a valuable additional targeted drug active in patients with FIP1L1/PDGFRA+ CEL

Hypereosinophilic syndromes

Hypereosinophilic syndromes (HES) constitute a rare and heterogeneous group of disorders, defined as persistent and marked blood eosinophilia (> 1.5 × 109/L for more than six consecutive months) associated with evidence of eosinophil-induced organ damage, where other causes of hypereosinophilia such as allergic, parasitic, and malignant disorders have been excluded. Prevalence is unknown. HES occur most frequently in young to middle-aged patients, but may concern any age group. Male predominance (4–9:1 ratio) has been reported in historic series but this is likely to reflect the quasi-exclusive male distribution of a sporadic hematopoietic stem cell mutation found in a recently characterized disease variant. Target-organ damage mediated by eosinophils is highly variable among patients, with involvement of skin, heart, lungs, and central and peripheral nervous systems in more than 50% of cases. Other frequently observed complications include hepato- and/or splenomegaly, eosinophilic gastroenteritis, and coagulation disorders. Recent advances in underlying pathogenesis have established that hypereosinophilia may be due either to primitive involvement of myeloid cells, essentially due to occurrence of an interstitial chromosomal deletion on 4q12 leading to creation of the FIP1L1-PDGFRA fusion gene (F/P+ variant), or to increased interleukin (IL)-5 production by a clonally expanded T cell population (lymphocytic variant), most frequently characterized by a CD3-CD4+ phenotype. Diagnosis of HES relies on observation of persistent and marked hypereosinophilia responsible for target-organ damage, and exclusion of underlying causes of hypereosinophilia, including allergic and parasitic disorders, solid and hematological malignancies, Churg-Strauss disease, and HTLV infection. Once these criteria are fulfilled, further testing for eventual pathogenic classification is warranted using appropriate cytogenetic and functional approaches. Therapeutic management should be adjusted to disease severity and eventual detection of pathogenic variants. For F/P+ patients, imatinib has undisputedly become first line therapy. For others, corticosteroids are generally administered initially, followed by agents such as hydroxycarbamide, interferon-alpha, and imatinib, for corticosteroid-resistant cases, as well as for corticosteroid-sparing purposes. Recent data suggest that mepolizumab, an anti-IL-5 antibody, is an effective corticosteroid-sparing agent for F/P-negative patients. Prognosis has improved significantly since definition of HES, and currently depends on development of irreversible heart failure, as well as eventual malignant transformation of myeloid or lymphoid cells

Direct comparison of distinct naive pluripotent states in human embryonic stem cells

Stem cells & developmental biolog