The Role of the Corneocyte Lipid Envelopes in Cohesion of the Stratum Corneum

Treatment of isolated stratum corneum with certain detergents results in complete disaggregation of the corneocytes within hours at 45°C without agitation. This is prevented by prior heating of the tissue to 80° C or by solvent extraction of the intercellular lipids. In the present study, electron micros- copy revealed that the heated or solvent-extracted tissue was characterized by cell-to-cell contacts that appeared to involve the chemically bound hydroxyceramides which constitute the corneocyte lipid envelope. It is proposed that the irreversible bonding between corneocytes that results from heating or lipid extraction results from interdigitation of the sphingosine chains belonging to those hydroxyceramides that are bound to the corneocyte protein envelope by the ω-hydroxyl function of the 30- and 32-carbon hydroxyacid moieties. Similar interdigitaion of adjacent envelopes might be involved in natural stratum corneum cohesion, limited mostly to the periphery of corneocytes where the absence of inter-cellular lamellae allows the appropriate cell-to-cell contact

GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia.

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P \u3c .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P \u3c .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors. © 2019 American Society of Hematology. All rights reserved

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Binuclear Complexes of Cobalt, Nickel and Copper and Activation of Molecular Oxygen by Transition Metal Complexes in the Oxidation of Olefinic Substrates

166 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1976.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Molecular models of the Intercellular Lipid Lamellae in Mammalian Stratum Corneum

Intercellular lipid lamellae in the stratum corneum constitute the barrier to water diffusion and may also play a role in cohesion between corneocytes. The lamellae arise from stacks of lamellar disks that are extruded from the granular cells and then fuse edge-to-edge to form sheets. It has been proposed that each lamellar disk is formed from a flattened vesicle, and therefore consists of two lipid bilayers in close apposition. In the present study, electron microscopic examination of ruthenium-tetroxide-fixed stratum corneum from mouse, pig, and human skin revealed that the double bilayer pattern persists in the intercellular lamellae. In addition, distinctive patterning of the intercellular lamellae has led us to propose novel molecular arrangements of the intercellular lipids. These include interlamellar sharing of lipid chains to produce lipid monolayers between pairs of bilayers. The pattern reflects the provenance of the intercellular lamellae from lamellar granule disks and the nonrandom orientation of the lamellar lipids

Family caregiving for persons with heart failure at the intersection of heart failure and palliative care: a state-of-the-science review.

Many of the 23 million individuals with heart failure (HF) worldwide receive daily, unpaid support from a family member or friend. Although HF and palliative care practice guidelines stipulate that support be provided to family caregivers, the evidence base to guide care for this population has not been comprehensively assessed. In order to appraise the state-of-the-science of HF family caregiving and recommend areas for future research, the aims of this review were to summarize (1) how caregivers influence patients, (2) the consequences of HF for caregivers, and (3) interventions directed at HF caregivers. We reviewed all literature to December 2015 in PubMed and CINAHL using the search terms "heart failure" AND "caregiver." Inclusion criteria dictated that studies report original research of HF family caregiving. Articles focused on children or instrument development or aggregated HF with other illnesses were excluded. We identified 120 studies, representing 5700 caregivers. Research on this population indicates that (1) caregiving situations vary widely with equally wide-ranging tasks for patients to help facilitate their health behaviors, psychological health and relationships, and quality of life (QoL); (2) caregivers have numerous unmet needs that fluctuate with patients' unpredictable medical status, are felt to be ignored by the formal healthcare system, and can lead to distress, burden, and reduced QoL; and (3) relatively few interventions have been developed and tested that effectively support HF family caregivers. We provide recommendations to progress the science forward in each of these areas that moves beyond descriptive work to intervention development and clinical trials testing