tbuckley/cabot-search huggingface dataset:
Corticosteroid Suppression of VEGF-A in Infantile Hemangioma-Derived Stem Cells
Authors: Shoshana Greenberger, Elisa Boscolo, Irit Adini, John B. Mulliken, Joyce Bischoff
Journal: New England Journal of Medicine (2010)

Corticosteroids are commonly used to treat infantile hemangioma, but the mechanism of action of this therapy is unknown. We investigated the effect of corticosteroids in a previously described in vivo model of infantile hemangioma and in cultured hemangioma-derived cells.We tested hemangioma-derived stem cells for vasculogenic activity in vivo after implantation into immune-deficient (nude) mice. We studied dexamethasone treatment of both the cells before implantation and the mice after implantation. We also tested hemangioma-derived stem cells for expression of vascular endothelial growth factor A (VEGF-A) in vitro and studied the inhibition of VEGF-A expression, using short hairpin RNA (shRNA) in vivo and in vitro.Systemic treatment with dexamethasone led to dose-dependent inhibition of tumor vasculogenesis in the murine model. Pretreatment of hemangioma-derived stem cells in vitro before implantation also inhibited vasculogenesis. Dexamethasone suppressed VEGF-A production by hemangioma-derived stem cells in vitro but not by hemangioma-derived endothelial cells or human umbilical-vein endothelial cells. Silencing VEGF-A in hemangioma-derived stem cells reduced vasculogenesis in vivo. VEGF-A was detected in hemangioma specimens in the proliferating phase but not in the involuting phase and was shown by immunostaining to reside outside of vessels. Corticosteroid treatment suppressed other proangiogenic factors in hemangioma-derived stem cells, including urokinase plasminogen activator receptor, interleukin-6, monocyte chemoattractant protein 1, and matrix metalloproteinase 1.In a murine model, dexamethasone inhibited the vasculogenic potential of stem cells derived from human infantile hemangioma. The corticosteroid also inhibited the expression of VEGF-A by hemangioma-derived stem cells, and silencing of VEGF-A expression in these cells inhibited vasculogenesis in vivo.
Secreted Chick Semaphorins Bind Recombinant Neuropilin with Similar Affinities but Bind Different Subsets of Neurons In Situ
Authors: Leonard Feiner, Adam M Koppel, Hiroaki Kobayashi, Jonathan A Raper
Journal: Neuron (1997)

Collapsin-1, a member of the semaphorin family, activates receptors on specific growth cones, thereby inhibiting their motility. Neuropilin, a previously cloned transmembrane protein, has recently been identified as a candidate receptor for collapsin-1. We have completed the cloning of chick collapsin-3 and -5 and show that collapsin-1, -2, -3, and -5 bind to overlapping but distinct axon tracts. We infer that in situ, there are distinct receptors with different affinities for collapsin-1, -2, -3, and -5. In contrast, these four collapsins all bind recombinant neuropilin with similar affinities. Strong binding to neuropilin is mediated by the carboxy third of the collapsins, while the semaphorin domain confers their unique binding patterns in situ. We propose that neuropilin is a common component of a semaphorin receptor complex, and that additional differentially expressed receptor components interact with the semaphorin domains to confer binding specificity.
SPECIFIC TRANSPLANTATION ANTIGENS OF MOUSE SARCOMAS INDUCED BY ADENOVIRUS TYPE 12
Authors: H. O. Sjögren, J. Minowada, J. Ankerst
Journal: The Journal of Experimental Medicine (1967)

A specific isograft resistance against three different mouse adeno 12 sarcomas was demonstrated in mice treated with four to eight doses of viable or X-ray-killed adeno 12 mouse tumors. Whole-body X-ray irradiation with 350 R 24 hr previous to the test challenge did not abolish the resistance, indicating that it was due to a true anamnestic immune reaction. This was further proven by the finding that similar treatment with tumors of other origin did not induce any immunity, nor did the treatment with adeno 12 tumor material induce any immunity against two neoplasms of Schmidt-Ruppin-Rous viral origin. The previous report by Trentin et al. (17) that adeno 12 infection leads to a specific transplantation immunity was fully confirmed. When the specificity of this virus-induced immunity was studied it was discovered that besides adeno virus type 12, type 7 and probably type 18 also gave the same type of resistance while adenovirus type 5 did not. A contamination of the adeno 7-infected mice with adeno type 12 was excluded by testing pooled sera from these animals for anti-adeno 12 CF or HI antibodies.
British Regional Heart Study: geographic variations in cardiovascular mortality, and the role of water quality
Authors: S J Pocock, A G Shaper, D G Cook, R F Packham, R F Lacey, P Powell, P F Russell
Journal: BMJ (1980)

In a study of regional variations in cardiovascular mortality in Great Britain during 1969-73 based on 253 towns the possible contributions of drinking water quality, climate, air pollution, blood groups, and socioeconomic factors were evaluated. A twofold range in mortality from stroke and ischaemic heart disease was apparent, the highest mortality being in the west of Scotland and the lowest in south-east England. A multifactorial approach identified five principal factors that substantially explained this geographic variation in cardiovascular mortality—namely, water hardness, rainfall, temperature, and two social factors (percentage of manual workers and car ownership). After adjustment for other factors cardiovascular mortality in areas with very soft water, around 0·25 mmol/l (calcium carbonate equivalent 25 mg/l), was estimated to be 10-15% higher than that in areas with medium-hard water, around 1·7 mmol/l (170 mg/l), while any further increase in hardness beyond 1·7 mmol/l did not additionally lower cardiovascular mortality. Thus a negative relation existed between water hardness and cardiovascular mortality, although climate and socioeconomic conditions also appeared to be important influences. Cross-sectional and prospective surveys of 7500 middle-aged men from 24 towns are in progress and will permit further exploration of these geographic differences, especially with regard to personal risk factors such as blood pressure, blood lipid concentrations, and cigarette smoking.
A TEACHING PROGRAM IN PUBLIC HEALTH PSYCHIATRY
Authors: JULES V. COLEMAN, CLAUDEWELL S. THOMAS, BERNARD J. BERGEN
Journal: American Journal of Psychiatry (1965)

We have discussed a teaching program in public health psychiatry from the point of view of a number of relevant issues in community practice and research. We have particularly stressed problems and issues in each of three areas, i.e., unmet psychiatric need, particularly in the lowest socioeconomic class, paths to treatment and the question of why people do or do not make use of psychiatric facilities and finally, the difficult and relatively new area of community organization and coordination of community resources for the complex variety of psychiatric disorders.
Association of clonally expanded T cells with the syndrome of primary biliary cirrhosis and limited scleroderma
Authors: Marlyn J. Mayo, Robert N. Jenkins, Burton Combes, Peter E. Lipsky
Journal: Hepatology (1999)

Clinical features of the CREST (calcinosis cutis, Raynaud's syndrome, esophageal dysmotility, sclerodactyly, and telangiectasias) syndrome are sometimes exhibited in patients with primary biliary cirrhosis (PBC), but the postulated autoimmune mechanisms behind these conditions are poorly understood. Clonally expanded T cells may play an important role in disease pathogenesis. In this study, overrepresentation of one T–cell receptor beta chain variable region, TCRBV3, was documented in patients with PBC and/or CREST. Overrepresentation of the TCRBV3 gene mRNA was demonstrated by semiquantitative reverse–transcriptase polymerase chain reaction (RT–PCR). T cells expressing TCRBV3 were analyzed by flow cytometry, were primarily CD8 + , and contained activated cells as assessed by expression of CD69. Clonally expanded T cells within this population were documented by both complementarity determining region 3 (CDR3) length polymorphism analysis and sequencing of T–cell receptor CDR3 cDNA. TCRBV3 + clonal expansions were stable when followed for up to 5 years. The results of this study demonstrate that the T–cell repertoire of patients with PBC and CREST is characterized by expanded clonal populations of CD8 + TCRBV3 + T cells. These clonal expansions provide evidence that stimulation of clonal populations of CD8 + T cells is associated with the clinical syndrome of PBC with CREST.
P242 What is the pre-admission NHS-consultation behaviour of adults with community-acquired pneumonia?: Abstract P242 Table 1.
Authors: M Akhtar, M Woodhead
Journal: Thorax (2013)

<h3>Introduction</h3> Under 75 mortality from respiratory disease is highlighted as a target in the NHS Outcomes Framework. Community-acquired pneumonia (CAP) cases are likely to form a considerable proportion of such deaths. Most CAP deaths occur in hospital, but it is not known whether initiatives to reduce such deaths should be primarily targeted at hospital or alternatively at pre-hospital care. To help address this we set out to identify the pre-admission NHS contact behaviour of adults admitted for CAP. <h3>Methods</h3> Adult admissions for CAP to one NHS Trust were prospectively identified between 14<sup>th</sup> May and 25<sup>th</sup> June 2013. For each case the diagnosis was validated by chest radiograph examination. After written informed consent a structured interview was conducted with each patient. Anonymous data was collected in an Excel spread-sheet and analysed with IBM SPSS 20. <h3>Results</h3> Of 83 possible pneumonia cases, 64 were confirmed to have radiographic pneumonia and 44 included in the study (Exclusions: declined - 4; language barrier - 4; immune compromise–5; unable to provide history due to illness or confusion–7). Median age was 73 years and CURB65 distribution was 0–1 (36%), 2 (30%), 3–5 (34%) - similar to the BTS audit population. Only 17 (38%) had had some form of pre-admission NHS contact for this illness, the majority presenting directly to hospital. Pre-admission NHS contacts included GP contact (17, including 9 consultations, 5 telephone contacts, 2 home visits, 1 out-of-hours service), 1 walk-in centre and 1 A &amp; E attendance. 1 case had 3 pre admission NHS contacts. There were no contacts with NHS Direct / 111. Those with sputum production, higher CURB65 scores and longer illness duration were significantly more likely to have had pre-admission NHS contact (Table). Multiple other factors (eg age, ethnicity, having English as first language, weekend admission, distance of home from hospital) were not significantly related to pre-admission behaviour. <h3>Conclusions</h3> The majority of admitted adult CAP cases presented directly to hospital, but a significant minority had pre-admission NHS contact. Efforts to reduce CAP mortality should primarily be directed at in-hospital care.
Synovial Fluid Glucose
Authors: Duncan S. Owen
Journal: JAMA (1978)

<h3>To the Editor.—</h3> I read with interest the article "Leukocytosis and Artifactual Hypoglycemia" (237:1961-1962, 1977). An analogous situation occurs in synovial fluid and needs to be emphasized. For example, on occasion synovial fluids from patients with rheumatoid arthritis and gout have leukocyte counts greater than 50,000 cells/cu mm. If the glucose determination is not done within an hour, the glycolytic action of the leukocytes can produce a value of 30 mg/dl or less, and the inexperienced clinician may make an erroneous diagnosis of septic arthritis. To avoid confusion and errors, we recommend that the synovial fluids to be used for glucose determinations be placed in a tube containing sodium fluoride.<sup>1,2</sup>Tubes containing sodium fluoride are commercially available.
Polymorphonuclear leucocyte function and previous yersinia arthritis: correlation of enhanced superoxide production with late manifestations.
Authors: H Repo, P Koivuranta-Vaara, M Leirisalo-Repo
Journal: Annals of the Rheumatic Diseases (1988)

Polymorphonuclear leucocyte (PMN) functions (migration in vitro, chemiluminescence, O-2 production, and aggregation) were studied in 32 patients with previous yersinia arthritis (YA). PMNs of 11 HLA-B27 positive patients who had chronic or recurrent inflammatory symptoms showed O-2 production significantly higher than that of PMNs of 11 HLA-B27 positive patients without late manifestations. Also, PMNs of both HLA-B27 positive and negative patients tended to show chemotactic and chemokinetic migration rates higher than those of control cells of healthy HLA-B27 negative subjects. These functional aberrations may play a part in the development of the patients9 inflammatory symptoms.
WEIGHT CHANGE AND ANGINA FREQUENCY IN PATIENTS PRESENTING WITH ACUTE MYOCARDIAL INFARCTION
Authors: Praneet Sharma, Donna Buchanan, Philip Jones, Stacie Daugherty, Faraz Kureshi, Natalie Jayaram, Javier Valle, Eric Dean Merrill, Fengming Tang, John Spertus
Journal: Journal of the American College of Cardiology (2014)
Surgical Management of Ventricular Aneurysm
Authors: Ellis Rolett
Journal: JAMA (1969)

Dr. David Pfaff, Senior Assistant Resident in Medicine, Jewish Hospital of St. Louis, and Assistant in Medicine, Washington University School of Medicine: A 56-year-old white, male, warehouse clerk was hospitalized because of the sudden onset of severe dyspnea two hours before admission. One year ago the patient was hospitalized because of chest pain, after which classic evidence of a predominantly anteroseptal myocardial infarction developed. Warfarin sodium therapy was instituted and he responded well to chlorothiazide drugs. The roentgenogram of the chest immediately prior to discharge showed a probable ventricular aneurysm that was confirmed by fluoroscopic examination. Two months after discharge the patient was hospitalized because of severe precordial pain. Serial electrocardiograms and enzyme determinations showed no changes and the patient was discharged after five days with a diagnosis of coronary failure. ST-segment elevation persisted in leads V<sub>2</sub>and V<sub>3</sub>. Five weeks prior to the present admission the patient
Letter from Vienna.
Authors: F. C. SCHAEFER
Journal: JAMA (1894)

Vienna, Nov. 18, 1894. <h3>To the Editor:</h3> —As the Behring remedy for diphtheria is causing a great commotion in medical circles throughout Europe, and probably also in the United States, it may be of interest to inform your readers of the status of the remedy on this side of the Atlantic, in so far as it is possible to get at the facts. I made daily visits until a few days ago, for three weeks at Professor Koch's barracks in Berlin where Dr. Kossel is conducting the treatment of diphtheria patients with Behring's blood serum, and am happy to be able to say that, in the main, the treatment of his cases has been followed by satisfactory results while the work there has aroused the interest of European physicians. Every day a number of different foreign physicians are to be met there who have come to investigate the progress of
Pediatric Mortality Due to Inborn Errors of Metabolism in Victoria, Australia: A Population-Based Study
Authors: Himanshu Goel
Journal: JAMA (2010)

To the Editor: Inborn errors of metabolism (IEM) constitute an important group of individually rare disorders, with a combined prevalence of 1:318 to 1:3760 live births in different populations.1-3 We assessed the population-based contribution of IEM to pediatric mortality in Victoria, Australia.
Genome Size Reduction in the Chicken Has Involved Massive Loss of Ancestral Protein-Coding Genes
Authors: A. L. Hughes, R. Friedman
Journal: Molecular Biology and Evolution (2008)

Both mean genomes size and the variance in genome size among species are smaller on average in birds (class Aves) than in the other tetrapod classes. In order to test whether loss of protein-coding genes has contributed to genome size reduction in birds, we compared the chicken genome and five mammalian genomes. Numbers of members (paralogs) were significantly lower in the chicken gene families than in the corresponding mammalian families. Phylogenetic analyses of chicken, mammal, and fish paralogs supported the hypothesis that chicken-specific loss of paralogs occurred much more frequently than mammal-specific gene duplications. Moreover, the phylogenetic analyses supported the hypothesis that a substantial majority of the paralogs lost in chicken originated from duplications prior to the most recent common ancestor of tetrapods and bony fishes. In addition to loss of paralogs, numerous gene families present in the mammalian genomes were missing in the chicken genome; over 1,000 of these families were found in bony fishes, implying presence of the family in the tetrapod ancestor. In the set of families with more members on average in the mammals than in the chicken, immune system function was associated with a greater degree of gene family size reduction in the chicken, consistent with other evidence that immune system gene families have become particularly compact in birds.
Bile duct stones and laparoscopic cholecystectomy
Authors: S Paterson-Brown, O J Garden
Journal: BMJ (1991)

and that associations with low infant growth rates are partly determined before birth.' It is not clear what D P Davies and J Matthes mean by "nutritional and metabolic stress."Whatever it is, for their explanation to be correct it would have to be independent of social class to explain our observations.In the Hertfordshire study birth weight and plasma glucose, insulin, and proinsulin concentrations were not related to social class, either at birth or currently.
Special Representative Meeting
Authors: F. Pygott
Journal: BMJ (1970)

Although the role of transforming growth factor β (TGFβ) in initiating fibrosis is well established, the role that TGFβ plays in maintaining fibrosis is unclear. The gene encoding connective tissue growth factor (ccn2; ctgf), which promotes fibrosis, is not normally expressed in dermal fibroblasts unless TGFβ is present. However, in dermal fibroblasts cultured from lesional areas of scleroderma, ccn2 (ctgf) is expressed constitutively. The contribution of several elements in the ccn2 (ctgf) promoter to basal and TGFβ induced ccn2 (ctgf) expression in normal and scleroderma fibroblasts has been investigated. A functional SMAD binding site in the ccn2 (ctgf) promoter that is necessary for the TGFβ mediated induction of this gene has been identified. The previously termed TGFβ responsive enhancer (TGFβRE) in the ccn2 (ctgf) promoter has been found to be necessary for basal promoter activity in normal fibroblasts. The SMAD element is not necessary for the high ccn2 (ctgf) promoter activity seen in scleroderma fibroblasts. However, mutation of the previously termed TGFβRE reduces ccn2 (ctgf) promoter activity in scleroderma fibroblasts to that seen in normal fibroblasts. Thus, the maintenance of the scleroderma phenotype, as assessed by a high degree of ccn2 (ctgf) promoter activity, appears to be relatively independent of SMAD action and seems to reflect increased basal promoter activity.
A novel function for a micro RNA: Negative regulators can do positive for the hepatitis C virus
Authors: Nicole Appel, Ralf Bartenschlager
Journal: Hepatology (2006)

MicroRNAs are small RNA molecules that regulate messenger RNA (mRNA) expression. MicroRNA 122 (miR-122) is specifically expressed and highly abundant in the human liver. We show that the sequestration of miR-122 in liver cells results in marked loss of autonomously replicating hepatitis C viral RNAs. A genetic interaction between miR-122 and the 5′ noncoding region of the viral genome was revealed by mutational analyses of the predicted microRNA binding site and ectopic expression of miR-122 molecules containing compensatory mutations. Studies with replication-defective RNAs suggested that miR-122 did not detectably affect mRNA translation or RNA stability. Therefore, miR-122 is likely to facilitate replication of the viral RNA, suggesting that miR-122 may present a target for antiviral intervention.
IT-01 * PD1/PDL1 INTERACTIONS MEDIATE SUPPRESSION OF ANTI-TUMOR IMMUNE ACTIVITY IN GLIOMA
Authors: J. Antonios, H. Soto, R. Harris, D. Nathanson, S. Sadeghi, B. Ellingson, L. Liau, R. Prins
Journal: Neuro-Oncology (2014)

Recent work has demonstrated that the interaction of the Programed Death-1 (PD1) negative costimulatory molecule with its ligand, PDL1 in the tumor microenvironment, plays an immunoregulatory role that may prevent the development of a successful anti-tumor response. We hypothesized that dendritic cell vaccination (DCVax) would induce a compensatory upregulation of PDL1 within the tumor microenvironment as a result of increased tumor infiltrating lymphocytes (TILs). We also hypothesized that simultaneous blockade of the PD1/ PDL1 interaction would promote a successful antitumor response. To test this, immunocompetent C57BL/6 mice were implanted with GL261 glioma cells in the brain. Mice were then stratified into 4 treatment groups (Tx on days 3 and 13 post-implant): (1) Control; (2) IP murine anti-PD1 mAb (10mg/kg) only; (3) subcutaneous GL261 lysate-pulsed DCVax only; and (4) combination (anti-PD1 mAb plus DCVax). Overall survival was quantified. On post-implant days 15 and 20, mice were imaged using a Bruker 7T MR scanner to obtain anatomical, perfusion, and pH-weighted data. On post-implant days 16 and 21, mice were imaged with [18F]-FAC PET to evaluate the lymphocyte response. Tumor-bearing hemisphere, spleen, and lymph node (LN) leukocytes were then harvested, processed, and stained for FACS analysis. Median survival of the combination group was significantly greater than the DCVax or PD-1 treatment groups (p < 0.005). MRI showed decreased tumor volume and inflammation in the combination group. FACS analysis and [18F]-PET demonstrated significantly enhanced numbers of activated lymphocytes accumulating within the cervical LN and tumor in PD-1 mAb, DCVax, and combination treatment groups. Elevated PDL1 expression on tumor-associated APCs was also noted in the DCVax group, but specifically lower in the combination group. We propose that PDL1 is upregulated within the tumor in response to immunotherapy, but can be blocked to restore effective anti-tumor immune responses.
Chester porphyria: a clinical study of a new form of acute porphyria.
Authors: M R Qadiri, S E Church, K E McColl, M R Moore, G R Youngs
Journal: BMJ (1986)

Acute porphyria afflicts a large kindred in Chester that stems from a marriage in 1896 that has produced 200 descendants; this is the largest porphyric kindred to be identified in the United Kingdom. Six members aged 51 or under died from the condition over the past eight years. The diagnosis of porphyria was overlooked in some as the symptoms may mimic those of other acute illnesses, so that incomplete or incorrect death certificates have been issued. Psychosis, hypertension, and renal complications are particularly common. The porphyric members of the kindred show a previously undescribed hereditary disorder in which the characteristic enzymatic defects of acute intermittent porphyria and variegate porphyria coexist in the same subject. Acute porphyria is poorly understood by hospital and general practitioners, and this has caused anxiety in the kindred. A register of the kindred has been established, and families at risk should be offered biochemical screening, education, and genetic counselling.