tbuckley/cabot-search huggingface dataset:
Consensus Conference Report
Authors: Jonathan G. Zaroff, Bruce R. Rosengard, William F. Armstrong, Wayne D. Babcock, Anthony D’Alessandro, G. William Dec, Niloo M. Edwards, Robert S. Higgins, Valluvan Jeevanandum, Myron Kauffman, James K. Kirklin, Stephen R. Large, Daniel Marelli, Tammie S. Peterson, W. Steves Ring, Robert C. Robbins, Stuart D. Russell, David O. Taylor, Adrian Van Bakel, John Wallwork, James B. Young
Journal: Circulation (2002)

The shortage of available donor hearts continues to limit cardiac transplantation. For this reason, strict criteria have limited the number of patients placed on the US waiting list to approximately 6000 to 8000 per year. Because the number of available donor hearts has not increased beyond approximately 2500 per year, the transplant waiting list mortality rate remains substantial. Suboptimal and variable utilization of donor hearts has compounded the problem in the United States. In 1999, the average donor yield from 55 US regions was 39%, ranging from 19% to 62%. This report provides the detailed cardiac recommendations from the conference on "Maximizing Use of Organs Recovered From the Cadaver Donor" held March 28 to 29, 2001, in Crystal City, Va. The specific objective of the report is to provide recommendations to improve the evaluation and successful utilization of potential cardiac donors. The report describes the accuracy of current techniques such as echocardiography in the assessment of donor heart function before recovery and the impact of these data on donor yield. The rationale for and specific details of a donor-management pathway that uses pulmonary artery catheterization and hormonal resuscitation are provided. Administrative recommendations such as enhanced communication strategies among transplant centers and organ-procurement organizations, financial incentives for organ recovery, and expansion of donor database fields for research are also described.
Genome-Environment Interactions That Modulate Aging: Powerful Targets for Drug Discovery
Authors: João Pedro de Magalhães, Daniel Wuttke, Shona H. Wood, Michael Plank, Chintan Vora
Journal: Pharmacological Reviews (2011)

Aging is the major biomedical challenge of this century. The percentage of elderly people, and consequently the incidence of age-related diseases such as heart disease, cancer, and neurodegenerative diseases, is projected to increase considerably in the coming decades. Findings from model organisms have revealed that aging is a surprisingly plastic process that can be manipulated by both genetic and environmental factors. Here we review a broad range of findings in model organisms, from environmental to genetic manipulations of aging, with a focus on those with underlying gene-environment interactions with potential for drug discovery and development. One well-studied dietary manipulation of aging is caloric restriction, which consists of restricting the food intake of organisms without triggering malnutrition and has been shown to retard aging in model organisms. Caloric restriction is already being used as a paradigm for developing compounds that mimic its life-extension effects and might therefore have therapeutic value. The potential for further advances in this field is immense; hundreds of genes in several pathways have recently emerged as regulators of aging and caloric restriction in model organisms. Some of these genes, such as <i>IGF1R</i> and <i>FOXO3</i>, have also been associated with human longevity in genetic association studies. The parallel emergence of network approaches offers prospects to develop multitarget drugs and combinatorial therapies. Understanding how the environment modulates aging-related genes may lead to human applications and disease therapies through diet, lifestyle, or pharmacological interventions. Unlocking the capacity to manipulate human aging would result in unprecedented health benefits.
Musashi1 regulates breast tumor cell proliferation and is a prognostic indicator of poor survival
Authors: Xiao-Yang Wang, Luiz OF Penalva, Hongyan Yuan, R Ilona Linnoila, Jiachun Lu, Hideyuki Okano, Robert I Glazer
Journal: Molecular Cancer (2010)

Musashi1 (Msi1) is a conserved RNA-binding protein that regulates the Notch and Wnt pathways, and serves as a stem cell marker in the breast and other tissues. It is unknown how Msi1 relates to other breast cancer markers, whether it denotes tumor initiating cells (TICs), and how it affects gene expression and tumor cell survival in breast cancer cells. Msi1 expression was analyzed in 20 breast cancer cell lines and in 140 primary breast tumors by western blotting and immunohistochemistry, respectively. Lentivirus RNA interference was used to reduce Msi1 expression in breast cancer cell lines MCF-7 and T47D grown as spheroid cultures and to assess stem cell gene expression and the growth of these cell lines as xenografts. In normal human breast tissue, Msi1 was expressed in 10.6% of myoepithelum and 1.2% of ductal epithelium in the terminal ductal lobular unit (TDLU), whereas, less than 0.05% of ductal epithelium and myoepithelium in large ducts outside the TDLU expressed Msi1. Msi1 was expressed in 55% of the breast cancer cell lines and correlated with ErbB2 expression in 50% of the cell lines. Msi1 was expressed in 68% of primary tumors and in 100% of lymph node metastases, and correlated with 5 year survival. Msi1 was enriched in CD133+ MCF-7 and T47D cells and in spheroid cultures of these cells, and Msi1 'knockdown' (KD) with a lentivirus-expressed shRNA decreased the number and size of spheroid colonies. Msi1 KD reduced Notch1, c-Myc, ErbB2 and pERK1/2 expression, and increased p21CIP1 expression, which is consistent with known Msi1 target mRNAs. Msi1 KD also reduced the expression of the somatic and embryonic stem cell markers, CD133, Bmi1, Sox2, Nanog and Oct4. Xenografts of MCF-7 and T47D Msi1 KD cells resulted in a marked reduction of tumor growth, reduced Msi1 and Notch1 expression and increased p21CIP1 expression. Msi1 is a negative prognostic indicator of breast cancer patient survival, and is indicative of tumor cells with stem cell-like characteristics. Msi1 KD reduces tumor cell survival and tumor xenograft growth, suggesting that it may represent a novel target for drug discovery.
Stool Bacteriomic Profiling in Patients with Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor–Tyrosine Kinase Inhibitors
Authors: Sumanta K. Pal, Sierra M. Li, Xiwei Wu, Hanjun Qin, Marcin Kortylewski, JoAnn Hsu, Courtney Carmichael, Paul Frankel
Journal: Clinical Cancer Research (2015)

Diarrhea occurs in approximately half of patients with metastatic renal cell carcinoma (mRCC) receiving vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKI). We evaluated the relationship between VEGF-TKI-related diarrhea and stool microbiota.Stool samples were collected from 20 mRCC patients receiving VEGF-TKIs. 16S rRNA sequencing was used to characterize the stool bacteriomic profiling of patients. Assay validation with Salmonella typhimurium spike-in experiments suggested greatest speciation with use of the V5 region.Higher levels of Bacteroides spp. and lower levels of Prevotella spp. were found in patients with diarrhea. In addition, patients receiving VEGF-TKIs with mRCC appeared to have less relative abundance of Bifidobacterium spp. as compared with previous reports based on healthy subjects.We have thus demonstrated interplay between microbiota and VEGF-TKI-induced diarrhea. Further studies are warranted to evaluate the potential causative role of preexisting dysbiosis in VEGF-TKI-related diarrhea.
Dramatic Change in Function and Expression Pattern of a Gene Duplicated by Polyploidy Created a Paternal Effect Gene in the Brassicaceae
Authors: S.-L. Liu, K. L. Adams
Journal: Molecular Biology and Evolution (2010)

New gene formation by polyploidy has been an ongoing process during the evolution of various eukaryotes that has contributed greatly to the large number of genes in their genomes. After duplication, some genes that are retained can acquire new functions or expression patterns, or subdivide their functions or expression patterns between duplicates. Here, we show that SHORT SUSPENSOR (SSP) and Brassinosteroid Kinase 1 (BSK1) are paralogs duplicated by a polyploidy event that occurred in the Brassicaceae family about 23 Ma. SSP is involved in paternal control of zygote elongation in Arabidopsis thaliana by transcription in the sperm cells of pollen and then translation in the zygote, whereas BSK1 is involved in brassinosteroid signal transduction. Comparative analysis of expression in 63 different organs and developmental stages revealed that BSK1 and SSP have opposite expression patterns in pollen compared with all other parts of the plant. We determined that BSK1 retains the ancestral expression pattern and function. Thus, SSP has diverged in function after duplication from a component of the brassinosteroid signaling pathway to a paternal regulator of the timing of zygote elongation. The ancestral function of SSP was lost by deletions in the kinase domain. Our sequence rate analysis revealed that SSP but not BSK1 has experienced a greatly accelerated rate of amino acid sequence changes and relaxation of purifying selection. In addition, SSP has been duplicated to create a new gene (SSP-like1) with a completely different expression pattern, a shorter coding sequence that has lost a critical functional domain, and a greatly accelerated rate of amino acid sequence evolution along with evidence for positive selection, together indicative of neofunctionalization. This study illustrates two dramatic examples of neofunctionalization following gene duplication by complete changes in expression pattern and function. In addition, our findings indicate that paternal control of zygote elongation by SSP is an evolutionarily recent innovation in the Brassicaceae family.
Intravascular lymphomatosis: a clinicopathologic study of 10 cases and assessment of response to chemotherapy.
Authors: J A DiGiuseppe, W G Nelson, E J Seifter, J K Boitnott, R B Mann
Journal: Journal of Clinical Oncology (1994)

PURPOSE We report a clinicopathologic study of 10 cases of intravascular lymphomatosis (IVL) seen at a single institution, and assess the response to chemotherapy in these patients, as well as those collected from a literature review. PATIENTS AND METHODS The clinical, pathologic, and immunophenotypic features of 10 cases of IVL diagnosed at the Johns Hopkins Hospital since 1977 were studied. Follow-up information was obtained in each case by consultation with the treating physician. In addition, cases of IVL reported previously in which patients were treated with chemotherapy and for which follow-up data were available at the time of publication were reviewed. RESULTS In the present series of 10 cases, the most common clinical features were fever of unknown origin (FUO), mental status changes, and rash. Diagnostic specimens were obtained from a variety of sources, including brain, skin, prostate, liver, kidney, and gallbladder. All of the four patients treated with combination chemotherapy are alive and two have achieved long-term survival (48 and 45 months, respectively); the remaining two are alive and in complete remission (CR) after short follow-up duration of 6 months. Among 35 patients reported in the literature who received chemotherapy (including four from this series), 43% attained a CR and were free of disease at the time of publication. None of the three patients in our series who received localized therapy (surgery with or without radiation therapy) is alive (mean survival duration, 9 months). For the three patients diagnosed at postmortem examination, the mean interval between onset of symptoms and death was 3 months, and disease was widespread. CONCLUSION These findings suggest that IVL represents a high-grade non-Hodgkin's lymphoma (NHL) with a propensity for systemic dissemination, and that CR and long-term survival may result in patients treated with aggressive combination chemotherapy.
Pulmonary hypertension secondary to neurofibromatosis: intimal fibrosis versus thromboembolism
Authors: N. Samuels, N. Berkman, E. Milgalter, J. Bar-Ziv, G. Amir, M. R Kramer
Journal: Thorax (1999)

Neurofibromatosis has been known to involve blood vessels throughout the body. Pulmonary involvement with interstitial fibrosing alveolitis has been described but no case of pulmonary vascular involvement has been reported to date. A 51 year old patient with cutaneous neurofibromatosis is described who presented with severe pulmonary hypertension and radiographic, scintigraphic, and angiographic evidence of chronic thromboembolic pulmonary hypertension. Severe intimal fibrosis consistent with vascular involvement with neurofibromatosis was found on endarterectomy with no evidence of pulmonary thromboembolism. Neurofibromatosis of pulmonary arteries should be considered as a possible cause of pulmonary hypertension.
Genetic regulation of delayed-type hypersensitivity responses to poly(LTyr,LGu)-poly(DLAla)--poly(LLys). I. Expression of the genetic defect at two phases of the immune process.
Authors: G Strassmann, Z Eshhar, E Mozes
Journal: The Journal of Experimental Medicine (1980)

Delayed-type hypersensitivity (DTH) responses served in this study as an experimental model for the analysis of genetic regulations of T-cell responses. Educated irradiated cells from H-2b mice mediated responses in syngeneic recipients, whereas mice of the a, d, f, k, and s haplotypes were nonresponders to poly(LTyr,LGlu)-poly(DLAla)--poly(LLys)[(T,G)-A--L]. These results suggest that cell-mediated immune responsiveness to (T,G)-A--L is linked to the H-2 complex, as was shown for humoral responses. Educated irradiated T cells of F1 hybrids between high and low responders mediated DTH responses, which indicates that the gene(s) controlling the DTH responses is dominant. To analyze the genetic defect in DTH responses to (T,G)-A--L, we separated the T-cell activation phase from the effector phase that was determined in recipient mice. Two types of nonresponders were observed: (a) When lymphocytes of the a or k haplotypes were educated in a syngeneic environment and then transferred into hybrids between the parental (nonresponder x responder) F1 recipients, DTH responses could have been manifested. (b) On the other hand, no DTH responses could be mediated by transferring educated cells of the H-2s or H-2f origin into the appropriate F1 recipients. In addition, irradiated F1 cells that had been activated to (T,G)-A--L could not mediate DTH responses in both types of nonresponder recipients. These results suggest that T cells of H-2k or H-2a mice can be activated to generate DTH responses to (T,G)-A--L and that the defect in these mouse strains is expressed in another cell population needed for the manifestation of the DTH reaction in the recipient mice. In contrast, T cells of H-2s and H-2f origin cannot be activated to (T,G)-A--L and, thus, fail to manifest DTH responses.
Trial of Early, Goal-Directed Resuscitation for Septic Shock
Authors: Paul R. Mouncey, Tiffany M. Osborn, G. Sarah Power, David A. Harrison, M. Zia Sadique, Richard D. Grieve, Rahi Jahan, Sheila E. Harvey, Derek Bell, Julian F. Bion, Timothy J. Coats, Mervyn Singer, J. Duncan Young, Kathryn M. Rowan
Journal: New England Journal of Medicine (2015)

Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains.We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days.We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%.In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.).
Greater trochanteric pain syndrome: defining the clinical syndrome
Authors: Angela M Fearon, Jennie M Scarvell, Terry Neeman, Jill L Cook, Wes Cormick, Paul N Smith
Journal: British Journal of Sports Medicine (2012)

Effective treatment of hip pain improves population health and quality of life. Accurate differential diagnosis is fundamental to effective treatment. The diagnostic criteria for one common hip problem, greater trochanteric pain syndrome (GTPS) have not been well defined.To define the clinical presentation of GTPS.Forty-one people with GTPS, 20 with hip osteoarthritis (OA), and 23 age-matched and sex-matched asymptomatic participants (ASC) were recruited. Inclusion and exclusion criteria ensured mutually exclusive groups.the Harris hip score (HHS), a battery of clinical tests, and single leg stance (SLS). Participants identified the site of reproduced pain.Fisher's exact test, analysis of variance (ANOVA) informed recursive partitioning to develop two classification trees.Maximum walking distance and the ability to manipulate shoes and socks were the only HHS domains to differentiate GTPS from OA (ANOVA: p=0.010 and <0.001); OR (95% CI) of 3.47 (1.09 to 10.93) and 0.06 (0.00 to 0.26), respectively. The lateral hip pain (LHP) classification tree: (dichotomous LHP associated with a flexion abduction external rotation (FABER) test) had a mean (SE) sensitivity and specificity of 0.81 (0.019) and 0.82 (0.044), respectively. A non-specific hip pain classification tree had a mean (SE) sensitivity and specificity of 0.78 (0.058) and 0.28 (0.080).Patients with LHP in the absence of difficulty with manipulating shoes and socks, together with pain on palpation of the greater trochanter and LHP with a FABER test are likely to have GTPS.
All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages
Authors: C. Seifart, J. P. Muyal, A. Plagens, A. O. Yildirim, K. Kohse, V. Grau, S. Sandu, C. Reinke, T. Tschernig, C. Vogelmeier, H. Fehrenbach
Journal: European Respiratory Journal (2011)

All-trans retinoic acid (ATRA) is controversially discussed in emphysema therapy. We re-evaluated ATRA in the elastase model and hypothesised that beneficial effects should be reflected by increased alveolar surface area, elastin expression and downregulation of inflammatory mediators and matrix metalloproteinases (MMPs). Emphysema was induced by porcine pancreatic elastase versus saline in Sprague-Dawley rats. On days 26-37, rats received daily intraperitoneal injections with ATRA (500 μg · kg(-1) body weight) versus olive oil. Lungs were removed at day 38. Rat alveolar epithelial L2 cells were incubated with/without elastase followed by ATRA- or vehicle-treatment, respectively. ATRA only partially ameliorated structural defects. Alveolar walls exhibited irregular architecture: increased arithmetic mean thickness, reduction in surface coverage by alveolar epithelial cells type II. ATRA only partially restored reduced soluble elastin. It tended to increase the ratio of ED1(+):ED2(+) macrophages. Bronchoalveolar lavage (BAL) cells exhibited a proinflammatory state and high expression of interleukin-1β, cytokine-induced neutrophil chemoattractant-1, tumour necrosis factor-α, nuclear factor-κB, MMP-2, MMP-9, MMP-12, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in emphysema, with ATRA exerting only few effects. MMP-7 was highly induced by ATRA in healthy but not in emphysematous lungs. ATRA reduced both MMP-2 and TIMP-1 activity in BAL fluid of emphysematous lungs. ATRA-therapy may bear the risk of unwanted side-effects on alveolar septal architecture in emphysematous lungs.
An In Vivo Analysis of Hematopoietic Stem Cell Potential
Authors: Richard P. Visconti, Yasuhiro Ebihara, Amanda C. LaRue, Paul A. Fleming, Tim C. McQuinn, Masahiro Masuya, Hitoshi Minamiguchi, Roger R. Markwald, Makio Ogawa, Christopher J. Drake
Journal: Circulation Research (2006)

Recent studies evaluating hematopoietic stem cell (HSC) potential raise the possibility that, in addition to embryonic sources, adult valve fibroblasts may be derived from HSCs. To test this hypothesis, we used methods that allow the potential of a single HSC to be evaluated in vivo. This was achieved by isolation and clonal expansion of single lineage-negative (Lin − ), c-kit + , Sca-1 + , CD34 − cells from the bone marrow of mice that ubiquitously express enhanced green fluorescent protein (EGFP) combined with transplantation of individual clonal populations derived from these candidate HSCs into a lethally irradiated congenic non-EGFP mouse. Histological analyses of valve tissue from clonally engrafted recipient mice revealed the presence of numerous EGFP + cells within host valves. A subpopulation of these cells exhibited synthetic properties characteristic of fibroblasts, as evidenced by their expression of mRNA for procollagen 1α1. Further, we show by Y-chromosome–specific fluorescence in situ hybridization analysis of female-to-male transplanted mice that the EGFP + valve cells are the result of HSC-derived cell differentiation and not the fusion of EGFP + donor cells with host somatic cells. Together, these findings demonstrate HSC contribution to the adult valve fibroblast population.
Smoking During Pregnancy, Vitamin C Supplementation, and Infant Respiratory Health
Authors: Graham L. Hall
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal