The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

https://ebmt.co.uk/wp-content/uploads/2013/08/GVHD1.pdf

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(08)60690-X.pdf

Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study.

MSCs are nonhematopoietic stromal cells that are capable of differentiating into, and contribute to the regeneration of, mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, and adipose. MSCs are rare in bone marrow, representing approximately 1 in 10,000 nucleated cells. Although not immortal, they have the ability to expand manyfold in culture while retaining their growth and multilineage potential. MSCs are identified by the expression of many molecules including CD105 (SH2) and CD73 (SH3/4) and are negative for the hematopoietic markers CD34, CD45, and CD14. The properties of MSCs make these cells potentially ideal candidates for tissue engineering. It has been shown that MSCs, when transplanted systemically, are able to migrate to sites of injury in animals, suggesting that MSCs possess migratory capacity. However, the mechanisms underlying the migration of these cells remain unclear. Chemokine receptors and their ligands and adhesion molecules play an important role in tissue-specific homing of leukocytes and have also been implicated in trafficking of hematopoietic precursors into and through tissue. Several studies have reported the functional expression of various chemokine receptors and adhesion molecules on human MSCs. Harnessing the migratory potential of MSCs by modulating their chemokine-chemokine receptor interactions may be a powerful way to increase their ability to correct inherited disorders of mesenchymal tissues or facilitate tissue repair in vivo. The current review describes what is known about MSCs and their capacity to home to tissues together with the associated molecular mechanisms involving chemokine receptors and adhesion molecules.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/epdf/10.1634/stemcells.2007-0197

Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing.

Small bowel obstruction exacerbated by barium sulfate administration

Book Review Neoplastic Diseases of the Blood Second edition. Edited by Peter H. Wiernik, George P. Canellos, Robert A. Kyle, and Charles A. Schiffer. 1028 pp., illustrated. New York, Churchill Livingstone, 1991. $189.95.

Presentation of Case A 32-year-old man was admitted to the clinic because of oral ulcerations. He was in excellent health until seven months earlier, when sneezing developed several weeks after the introduction of cats into his home. Skin tests yielded reactions to pollen, ragweed, and cat and dog dander. A hyposensitization program was begun, but after the fourth injection mild wheezing and a severe sore throat occurred; the injections were discontinued. An x-ray film of the chest was normal. Five months before admission the patient noticed ulcers on and beneath the tongue. A hydrogen peroxide mouthwash and orally administered penicillin . . .

Case 26-1980

It has been known for some time that “activated” macrophages obtained from immune animals have altered morphology and metabolism, and that they show enhanced capacities to deal with a number of microorganisms (1,2). A number of these studies have shown that the lymphocyte is involved in these activation processes (3,4). Their action can be partially explained by the production of soluble mediators such as macrophage activating factor (MAF) which increases the capacity of macrophages to kill bacteria and tumor cells (5,6). This factor cannot be distinguished from migration inhibitory factor (MIF) (7,8,9).

Philip L. McCarthy

Papers

Small bowel obstruction exacerbated by barium sulfate administration

Book Review Neoplastic Diseases of the Blood Second edition. Edited by Peter H. Wiernik, George P. Canellos, Robert A. Kyle, and Charles A. Schiffer. 1028 pp., illustrated. New York, Churchill Livingstone, 1991. $189.95.

Case 26-1980

Studies on MIF and the Role of Macrophage Associated Esterases in the Response of the Macrophage to MIF