tbuckley/cabot-search huggingface dataset:
Genes that Confer the Identity of the Renin Cell
Authors: Eric W. Brunskill, Maria Luisa S. Sequeira-Lopez, Ellen S. Pentz, Eugene Lin, Jing Yu, Bruce J. Aronow, S. Steven Potter, R. Ariel Gomez
Journal: Journal of the American Society of Nephrology (2011)

Renin-expressing cells modulate BP, fluid-electrolyte homeostasis, and kidney development, but remarkably little is known regarding the genetic regulatory network that governs the identity of these cells. Here we compared the gene expression profiles of renin cells with most cells in the kidney at various stages of development as well as after a physiologic challenge known to induce the transformation of arteriolar smooth muscle cells into renin-expressing cells. At all stages, renin cells expressed a distinct set of genes characteristic of the renin phenotype, which was vastly different from other cell types in the kidney. For example, cells programmed to exhibit the renin phenotype expressed Akr1b7, and maturing cells expressed angiogenic factors necessary for the development of the kidney vasculature and RGS (regulator of G-protein signaling) genes, suggesting a potential relationship between renin cells and pericytes. Contrary to the plasticity of arteriolar smooth muscle cells upstream from the glomerulus, which can transiently acquire the embryonic phenotype in the adult under physiologic stress, the adult juxtaglomerular cell always possessed characteristics of both smooth muscle and renin cells. Taken together, these results identify the gene expression profile of renin-expressing cells at various stages of maturity, and suggest that juxtaglomerular cells maintain properties of both smooth muscle and renin-expressing cells, likely to allow the rapid control of body fluids and BP through both contractile and endocrine functions.
An Evaluation of Methods of Assessing Impaired Awareness of Hypoglycemia in Type 1 Diabetes
Authors: Jacqueline Geddes, Rohana J. Wright, Nicola N. Zammitt, Ian J. Deary, Brian M. Frier
Journal: Diabetes Care (2007)

Subjective recognition of the warning symptoms of hypoglycemia is fundamental to allow self-treatment and prevent progression to severe hypoglycemia (1,2). Recognition of the onset of these premonitory symptoms constitutes awareness of hypoglycemia (3). With increasing duration of insulin therapy, many people with type 1 diabetes experience a change in their hypoglycemia awareness associated with either a reduction in symptom intensity or a change in symptom profile or both (3–6). Impaired awareness of hypoglycemia (IAH) is associated with a sixfold greater frequency of severe hypoglycemia and is a recognized risk factor for this problem (7,8).

Accurate identification of individuals with IAH is important to allow modification of glycemic targets and to adjust insulin therapy to minimize hypoglycemia risk. Three methods have been proposed to assess awareness of hypoglycemia for clinical application (7–9) but to date have not been compared directly. The present study was performed in a randomly selected cohort of individuals with type 1 diabetes to assess the concordance between these methods in ascertaining the prevalence of IAH and whether the methods have equivalent sensitivity in identifying affected individuals.

A total of 140 participants were recruited; 80 completed the study. Those who completed the study were significantly older than those who did not ( n = 60) (mean ± SD age 47.6 ± 12.7 vs. 41.1 ± 12.6 years, respectively, P = 0.04). No differences in duration of diabetes ( P = 0.7) or in glycemic control ( P = 0.35) were observed between these two groups. All completed a questionnaire to assess awareness of hypoglycemia using each of the methods presented by Gold et al. …
Anatomy of striae
Authors: P. ZHENG, R. M. LAVKER, A. M. KLIGMAN
Journal: British Journal of Dermatology (1985)

The histopathology of striae distensae is disputed; different authorities give contradictory accounts of the microscopic changes, especially in elastic fibres. We re-evaluated the problem by taking eight elliptical biopsies across striae. Six were examined by light microscopy with appropriate stains for elastin and collagen. Two were prepared for scanning electronmicroscopy (s.e.m.), using a procedure which removes collagen, enabling the elastic network to be seen in its native form. By light microscopy, striae were sharply demarcated from normal skin, consisting mainly of fine, straight bundles of collagen arranged parallel to the surface. Fine elastic fibres were disposed similarly without fragmentation, fraying or curling. By s.e.m., the elastic network was found to be extraordinarily dense and well developed with many fine, curled fibres in random array. It was evident that the routine stains for elastin greatly underestimated the abundance of elastic fibres, probably because immature fibres contain insufficient protein matrix. The horizontal packing of collagen bundles was confirmed by s.e.m. These findings support the view that striae distensae are scars. There is no evidence that they form by stress-induced rupture of the connective tissue.
Breast Cancer Expressing the Activated HER2/neu Is Sensitive to Gefitinib <i>In vitro</i> and <i>In vivo</i> and Acquires Resistance through a Novel Point Mutation in the HER2/neu
Authors: Marie P. Piechocki, George H. Yoo, Susan K. Dibbley, Fulvio Lonardo
Journal: Cancer Research (2007)

Abstract The HER2/neu oncogene is an important diagnostic and prognostic factor and therapeutic target in breast and other cancers. We developed and characterized a breast cancer cell line (Bam1a) that overexpresses the activated HER2/neu and ErbB-3 and has a gene expression profile consistent with the ErbB-2 genetic signature. We evaluated the effects of the epidermal growth factor receptor (EGFR)/HER2 inhibitor, gefitinib, on this breast tumor line in vitro and in vivo. We characterized the effects of gefitinib on EGFR, HER2, and ErbB-3 phosphorylation by Western blot and determined the effects on downstream signaling through growth, survival, and stress pathways and the effect on proliferation, cell cycle, and apoptosis. Gefitinib treatment diminished phosphorylation of the ErbB-3 &amp;gt; EGFR &amp;gt; HER2/neu and signal transducers and activators of transcriptions in a dose-dependent fashion. Downstream mitogenic signaling through mitogen-activated protein (MAP)/extracellular signal regulated kinase kinase, p44/42 MAP kinase (MAPK) and stress signaling through c-Jun-NH2-kinase (JNK) 1 and c-Jun was impaired (1 μmol/L, 4–24 h), leading to cytostasis and cell cycle arrest within 24 h by decreased cyclin D1, cyclin B1, and pSer795Rb and increased p27. Proliferation and colony formation were inhibited at 0.5 and 1 μmol/L, respectively, and correlated with altered gene expression profiles. Diminished survival signaling through Akt, induction of bim, loss of connexin43, and decreased production of vascular endothelial growth factor-D preceded caspase-3 and poly(ADP)ribose polymerase (PARP) cleavage and apoptosis (&amp;gt;50% 2 μmol/L, 48 h). Oral administration of gefitinib was able to prevent the outgrowth of Bam1a tumor cells from palpable lesions, shrink established tumors, eliminate HER2 and HER3 phosphorylation, and decrease MAPK and Akt signaling in vivo. A variant of the Bam1a cell line, IR-5, with acquired ability to grow in 5 μmol/L gefitinib was developed and characterized. IR-5 bears a novel point mutation in the HER2/neu that corresponds to a L726I in the ATP-binding pocket and correlates with a log decrease in sensitivity to gefitinib, increased heterodimerization with EGFR and HER3, and impaired down-regulation. Gene expression profiling of IR-5 showed increased expression of EMP-1, NOTCH-1, FLT-1, PDGFB, and several other genes that may contribute to the resistant phenotype and sustain signaling through MAPK and Akt. This model will be useful in understanding the differences between intrinsic drug sensitivity and acquired resistance in the context of therapeutic strategies that target oncogene addicted diseases. [Cancer Res 2007;67(14):6825–43]
Colon Polyps in Asymptomatic Persons
Authors: Donald R. Varner
Journal: Annals of Internal Medicine (1989)

Letters and Corrections15 July 1989Colon Polyps in Asymptomatic PersonsDonald R. Varner Jr., MD, USAF, Mark W. Wolfe, MD, USAF, Geoffery A. Patrissi, MADonald R. Varner Jr., MD, USAFSearch for more papers by this author, Mark W. Wolfe, MD, USAFSearch for more papers by this author, Geoffery A. Patrissi, MASearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-111-2-187_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:We read with great interest the recent article by Achkar and Carey (1) and the accompanying editorial by Waye (2). The clinical significance of hyperplastic polyps in the left colon predicting pre-malignant-malignant histology on the right is certainly controversial with the finding by Zauber and colleagues (3) of a relative risk of only 1.2 (not significant). Achkar and Carey report an incidence of neoplastic polyps proximally in 29% of patients with solely hyperplastic polyps on sigmoidoscopic examination. The main concern raised by Waye is that this incidence corresponds very closely to a combined autopsy incidence of 30%...References1. AchkarCarey EW. Small polyps found during fiberoptic sigmoidoscopy in asymptomatic patients. Ann Intern Med. 1988;109:880-3. LinkGoogle Scholar2. Waye J. Hyperplastic colon polyps—are they markers? [Editorial]. Ann Intern Med. 1988;109:851-2. LinkGoogle Scholar3. ZauberWinawerDiaz ASB. The National Polyp Study (NPS) : the association of colonic hyperplastic polyps and adenomas [Abstract]. Am J Gastroenterol. 1988;83:1060. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Keesler AFB, MS 39534-5300 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1989Volume 111, Issue 2Page: 187-187KeywordsAutopsyColonHistologyRelative risk Issue Published: 15 July 1989 PDF downloadLoading ...
Effect of endotoxin on fibronectin and kupffer cell activity
Authors: Peter S. Richards, Thomas M. Saba
Journal: Hepatology (1985)

The phagocytic activity of the reticuloendothelial system (RES) in the liver is important in host resistance to shock. Fibronectin is a large molecular weight glycoprotein which influences particulate uptake by phagocytic cells. This study addressed the effect of repeated low–dose endotoxin challenge on immunoreactive fibronectin and reticuloendothelial phagocytic function in rats. Intravenous Escherichia coli endotoxin increased circulating immunoreactive fibronectin by 100% within 24 hr; normalization was within 96 hr. Elevated fibronectin levels at 48 hr were associated with increased plasma opsonic activity as tested by liver slice phagocytic assay and RES stimulation, and in vitro uptake of gelatinized target particles by Kupffer cells in liver slices from endotoxin treated rats was significantly increased. Endotoxin tolerance was produced by repeated low dose challenge with endotoxin for 7 days and was associated with RES stimulation, even though the circulating fibronectin concentrations had returned to normal. By immunofluorescence, insoluble fibronectin was widely distributed in the liver in a pattern analogous to the sinusoidal vascular network. We suggest that increased RES phagocytic activity after low dose endotoxin challenge is due to early elevation of plasma fibronectin and cellular stimulation of phagocytic function followed by a sustained stimulation of Kupffer cells in the presence of normal fibronectin levels. Both cellular and humoral factors may contribute to increased Kupffer cell phagocytic activity during endotoxin tolerance.
Decline in Cognitive Performance Between Ages 13 and 18 Years and the Risk for Psychosis in Adulthood
Authors: James H. MacCabe, Susanne Wicks, Sofia Löfving, Anthony S. David, Åsa Berndtsson, Jan-Eric Gustafsson, Peter Allebeck, Christina Dalman
Journal: JAMA Psychiatry (2013)

Context: Clear evidence from many prospective, population-based studies indicates that patients who develop psychosis in adulthood experienced various cognitive deficits during childhood and adolescence.However, it is unclear whether these deficits become more severe during adolescence.Objective: To assess the influence of cognitive developmental trajectories in adolescence and young adulthood on the risk for psychosis in adulthood.
The Molecular Basis of Self-Avoidance
Authors: S. Lawrence Zipursky, Wesley B. Grueber
Journal: Annual Review of Neuroscience (2013)

Self-avoidance, the tendency of neurites of the same cell to selectively avoid each other, is a property of both vertebrate and invertebrate neurons. In Drosophila, self-avoidance is mediated by a large family of cell recognition molecules of the immunoglobulin superfamily encoded, via alternative splicing, by the Dscam1 locus. Dscam1 promotes self-avoidance in dendrites, axons, and prospective postsynaptic elements. Expression analysis suggests that each neuron expresses a unique combination of isoforms. Identical isoforms on sister neurites exhibit isoform-specific homophilic recognition and elicit repulsion between processes, thereby promoting self-avoidance. Although any isoform can promote self-avoidance, thousands are necessary to ensure that neurites readily discriminate between self and nonself. Recent studies indicate that a large family of cadherins in the mouse, i.e., the clustered protocadherins, functions in an analogous fashion to promote self-avoidance. These studies argue for the evolution of a common molecular strategy for self-avoidance.
Emergence of the N.H.S
Authors: A. T. Rogers
Journal: BMJ (1952)

<h3>BACKGROUND AND PURPOSE:</h3> There are few articles characterizing cerebellar lesions in patients with TSC and no published series documenting longitudinal evaluation of these lesions, to our knowledge. Recent suggestion of a correlation between autism and cerebellar lesions in patients with TSC heightens the importance of understanding these lesions. Our purpose was to characterize cerebellar lesions in a cohort of young patients with TSC with specific interest in assessing longitudinal changes. <h3>MATERIALS AND METHODS:</h3> We retrospectively reviewed MR images from 145 pediatric and young adult patients with tuberous sclerosis (mean age, 7.6 years). A number of imaging characteristics of cerebellar tubers were recorded, and patients were evaluated for SGAs. Patients with follow-up scans &gt;3 months from the original scan were further analyzed for longitudinal tuber characterization. <h3>RESULTS:</h3> There were 24.1% of patients with focal cerebellar lesions; 52.4% of patients with cerebellar lesions demonstrated change in imaging characteristics during longitudinal analysis. Fifty-one percent of the lesions were enhanced after gadolinium administration. Twenty percent of the patients with cerebellar lesions had pathologically confirmed SGAs compared with the incidence of 11% in the 145 patients with TSC reviewed. <h3>CONCLUSIONS:</h3> In our large cohort of young patients with TSC, cerebellar tubers were common and 52% of patients had tubers that changed with time. A higher percentage of patients with cerebellar lesions developed SGAs than patients with TSC without cerebellar lesions. Because this is the first reported longitudinal study of cerebellar lesions in TSC, further investigation may provide additional insight into TSC pathology and associated clinical manifestations, such as autism, developmental delay, and seizures.
Fostering Early Brain Development
Authors: W. Thomas Boyce
Journal: JAMA (2015)

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A child with severe relapsing Kawasaki disease rescued by IL-1 receptor blockade and extracorporeal membrane oxygenation
Authors: Sophie Cohen, Carline E Tacke, Bart Straver, Natasja Meijer, Irene M Kuipers, Taco W Kuijpers
Journal: Annals of the Rheumatic Diseases (2012)

Kawasaki disease (KD) is an acute inflammatory vasculitis that predominantly occurs in children under 5 years of age.1 It is associated with the development of coronary artery aneurysms (CAA) in 15–25% of untreated cases.2 Standard treatment consists of high-dose intravenous immunoglobulins (IVIG) along with aspirin.3 About 15% of patients do not respond to a single dose of IVIG and need retreatment.4 When ongoing signs of active disease are present, methylprednisolone pulses are often administered.5 If there is a lack of response, alternative anti-inflammatory medication such as infliximab or plasmapheresis have been suggested in individual case series.6 ,7 We report, for the first time, the beneficial use of an interleukin-1 receptor antagonist (IL-1RA) in relapsing KD.

A 2-year-old boy was presented with persistent fever, coughing and swollen cervical lymph nodes. The boy's condition had not improved with empirical antibiotic treatment. He developed a rash, conjunctivitis and swollen extremities. Upon admission the …
Dynamic hyperinflation after bronchial lung volume reduction: An expected effect or perhaps a preoperative test for selection?
Authors: Sergio Baldi, Francesco Coni, Paolo Solidoro, Alessio Mattei, Marco Bardessono
Journal: European Respiratory Journal (2013)

Introduction  In our center we have treated with bronchial valves (Zephyr model) 35 patients suffering from advanced emphysema, with variable results. This is a preliminary report that refers to 14 patients who were studied for the presence of dynamic hyperinflation, evaluating the inspiratory capacity (IC) before and at the end of a submaximal effort (ΔIC).  Methods  After assessing the whole group we analyzed two different subgroups on the basis of dynamic hyperinflation. Group1 included 10 patients with dynamic hyperinflation (ΔIC reduced>10%); group2 included 4 patients without dynamic hyperinflation (ΔIC reduced  Results at 6 month are in the tables  Conclusion  The dynamic hyperinflation seems reduced after BLVR in the whole group (ΔIC from  -24% to -19%; (Table 1), but this data is not statistically significant; interestingly 10 patients in group 1 seem to have better results compared to 4 patients in group 2; in particular they have a better improvement of RV and ΔIC (Table 2). These preliminary data seem to propose dynamic hyperinflation as one of selection criteria for BLVR. A larger group of patients need to be examined to verify these data.
Past, Present, and Future Challenges in Breast Cancer Treatment
Authors: George W. Sledge, Eleftherios P. Mamounas, Gabriel N. Hortobagyi, Harold J. Burstein, Pamela J. Goodwin, Antonio C. Wolff
Journal: Journal of Clinical Oncology (2014)

The past half century—the lifetime of the American Society of Clinical Oncology—represents a historical watershed in the management of breast cancer, a period in which old dogmas were overthrown, to be replaced by biology-driven therapeutic approaches. These approaches transformed the disease from one where mutilating local therapy was followed by distant recurrence and death, to one where patients regularly choose local (and often minimal) therapy, then receive systemic therapies that are increasingly effective and progressively more targeted. Breast cancer, perhaps more than any other solid tumor, was transformed by the progressive application of clinical hypothesis testing of basic biologic concepts. The revolutionary overthrow of the Halstedian hypothesis, with its emphasis on the primacy of locoregional control through extensive surgery, led to changes both in locoregional therapy as well as providing the intellectual basis for adjuvant systemic therapies. And, at a time when systemic therapies were dominated by rank empiricism, breast cancer led the way in the application of targeted biologic therapy, long before targeted therapy became an oncologic mantra. This article will review a half-century of progress, focusing on the areas in which the greatest progress has been seen: the revolution in locoregional therapy; the application of cytotoxic chemotherapy in both local and advanced disease; the discovery and therapeutic exploitation of estrogen receptor biology; the use of estrogen receptor biology for breast cancer prevention; and the targeting of the human epidermal growth factor receptor complex. Collectively, these constitute a revolution in breast cancer therapeutics that has occurred within the lifetime of an organization. Finally, we will touch on the remaining therapeutic challenges for this disease. Locoregional Therapy The locoregional treatment of breast cancer has been transformed through changes in both the biologic understanding and the clinical presentation of the disease. Starting with the pivotal randomized clinical trials from the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the Milan group, radical mastectomy was replaced by modified radical mastectomy and eventually breastconserving surgery, with breast radiation becoming the preferred
Opsonization of Apoptotic Cells by Autologous iC3b Facilitates Clearance by Immature Dendritic Cells, Down-regulates DR and CD86, and Up-regulates CC Chemokine Receptor 7
Authors: Inna Verbovetski, Hila Bychkov, Uriel Trahtemberg, Itzhak Shapira, Mara Hareuveni, Ofira Ben-Tal, Ina Kutikov, Oranit Gill, Dror Mevorach
Journal: The Journal of Experimental Medicine (2002)

Immature dendritic cells (iDCs) do not mature after uptake of apoptotic cells and may play a role in the induction of peripheral tolerance to self antigens derived from apoptotic material. The integrins, αvβ3, αvβ5, and the scavenger receptor, CD36, have been shown to mediate uptake of apoptotic cells by iDCs. However, it is not known whether the complement system, also takes part in this process. In this study we investigated the ability of iDCs to bind to apoptotic cells opsonized by iC3b. Monocyte-derived dendritic cells were offered apoptotic Jurkat cells opsonized by autologous iC3b and labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl-indocarbocyanineperchlorate. A significant increase (P &amp;lt; 0.001) in the amount of cleared apoptotic cells was seen at low ratios. Despite increased efficiency of uptake, interaction between iC3b-opsonized apoptotic cells and iDCs down-regulated the expression of major histocompatibility complex class II, CD86, CC chemokine receptor (CCR)2, CCR5, and β2-integrins (P &amp;lt; 0.001), and up-regulated expression of CCR7 (P &amp;lt; 0.001). In addition, iDC maturation responses to CD40L and lipopolysaccharide were significantly inhibited. We conclude that opsonization of apoptotic cells by iC3b induces tolerant iDCs that are able to migrate to lymph nodes.