tbuckley/cabot-search huggingface dataset:
Synthesis and release of erythroid colony- and burst-potentiating activities by purified populations of murine peritoneal macrophages
Authors: JI Kurland, PA Meyers, MAS Moore
Journal: The Journal of Experimental Medicine (1980)

We investigated the effects of murine resident peritoneal macrophages on the in vitro proliferation of erythropoietin (Ep)-sensitive committed precursors colony-forming unit-erythroid (CFU-E) and burst-forming unit-erythroid (BFU-E) with a two-layer cloning system of methylcellulose and semisolid agar. The addition of increasing numbers of macrophages to the agar underlayer resulted in a progressive increase in the numbers of both CFU-E and BFU-E that proliferated in the presence of Ep. CFU-E, but not BFU-E, proliferated to form colonies in the absence Qf exogenously added Ep, and this proliferation was enhanced in a dose-dependent fashion by the presence of macrophages in the underlayer. The enhancing effects of a given number of macrophages and a given concentration of Ep were greater than the sum of the individual effects of macrophages and Ep alone. This erythropoietic syngerism was more evident with BFU-E because burst formation was not seen in the absence of exogenously added Ep. Macrophage underlayers stimulated three to five times the number of erythroid bursts seen with Ep alone. Cell-free agar underlayers or agar underlayers prepared with nonadherent peritoneal cells or unseparated cells from thymus, lymph node, or spleen failed to augment Ep- dependent erythroid colony formation. No enhancement of CFU-E or BFU-E was demonstrable after depletion ofadherent cells from peritoneal cell suspensions by passage over columns of Sephadex G-10. Analysis by sedimentation velocity of peritoneal cells confirmed that the cells responsible for elaborating the erythroid-enhancing activity were macrophages on the basis of morphologic, histochemical, and functional criteria. Serum- free media conditioned by macrophages in the absence of Ep contained the erythroid-enhancing activities, which indicated that Ep was not required for the elaboration of these diffusible substances. These studies indicate that although macrophages are not obligate for the growth of erythroid precursors, they serve as an important source of diffusible factors that reduce the in vitro requirement for Ep.
Childhood Neuromuscular Disorders
Authors: P. K. Thomas
Journal: BMJ (1970)

perform the investigation and interpret -the films.It is an extremely thorough review condensed into a short readable book with many excellent illustrations.The most in- structive sections are those that deal with practical techniques-especially the methods of selective catheterization of the tribu- taries-and the pitfalls of interpretation.This book should be in the office of all vascular radiologists, and is worthy of study by both physicians and surgeons, who would quickly learn the great value of this simple but neglected and underrated method of clinical investigation.
Late-Onset Agoraphobia: General Population Incidence and Evidence for a Clinical Subtype
Authors: Karen Ritchie, Joanna Norton, Anthony Mann, Isabelle Carrière, Marie-Laure Ancelin
Journal: American Journal of Psychiatry (2013)

Objective The purpose of this study was to estimate the general population incidence of late-life agoraphobia and to define its clinical characteristics and risk factors. Method A total of 1,968 persons ≥65 years old were randomly recruited from the electoral rolls of the district of Montpellier, France. Prevalent and incident agoraphobia diagnosed with a standardized psychiatric examination and validated by a clinical panel were assessed at baseline and over a 4-year follow-up. Results The 1-month baseline prevalence of agoraphobia was estimated to be 10.4%. Among persons with agoraphobia, 10.9% reported having their first episode at age 65 or above. During the 4-year follow-up, 11.2% of participants without agoraphobia at baseline had a first episode, resulting in an incidence rate of 32 per 1,000 person-years. These 132 incident late-onset cases were associated with higher incidence rates of anxiety disorders and suicidal ideation. Of the incident cases, only two were characterized by past or concurrent panic attacks, a rate that was not significantly different from that of the noncase group. The principal baseline risk factors for incident cases, derived from a multivariate model incorporating all significant risk factors, were younger age at onset (odds ratio=0.94, 95% CI=0.90–0.99), poorer visuospatial memory performance (odds ratio=1.60, 95% CI=1.02–2.49), severe depression (odds ratio=2.62, 95% CI=1.34–5.10), and trait anxiety (odds ratio=1.73, 95% CI=1.03–2.90). No significant association was found with cardiac pathologies. Conclusions Agoraphobia has a high prevalence in the elderly, and unlike cases in younger populations, late-onset cases are not more common in women and are not associated with panic attacks, suggesting a late-life subtype. Severe depression, trait anxiety, and poor visuospatial memory are the principal risk factors for late-onset agoraphobia.
Identification of the ligand-binding domains of CD22, a member of the immunoglobulin superfamily that uniquely binds a sialic acid-dependent ligand.
Authors: P Engel, N Wagner, A S Miller, T F Tedder
Journal: The Journal of Experimental Medicine (1995)

CD22 is a B cell-restricted member of the immunoglobulin (Ig) superfamily that functions as an adhesion receptor for leukocytes and erythrocytes. CD22 is unique among members of the Ig superfamily in that it has been suggested to bind a series of sialic acid-dependent ligands, potentially through different functional domains expressed by different splice variants of CD22. In this study, the epitopes identified by a large panel of function-blocking and non-function-blocking CD22 monoclonal antibodies were localized to specific Ig-like domains, revealing that all function-blocking monoclonal antibodies bound to the first and/or second Ig-like domains. Consistent with a single ligand-binding region, the two amino-terminal domains were the functional unit that mediated CD22 adhesion with lymphocytes, neutrophils, monocytes, and erythrocytes. The predominant cell surface species of CD22 was a full length 140,000 relative molecular mass seven Ig-like domain glycoprotein and a minor 130,000 relative molecular mass form lacking the fourth domain. While the two amino-terminal Ig-like domains of CD22 are structurally similar to those found in other members of the Ig superfamily involved in cell adhesion and containing an amino acid sequence motif associated with integrin recognition, site-directed mutagenesis of critical residues surrounding this motif did not disrupt CD22-mediated adhesion. These results demonstrate that the unique ligand-binding properties of CD22 are distinct from those of other members of the Ig superfamily involved in integrin-mediated cell adhesion.
Expert consensus: time for a change in the way we advise our patients to use topical corticosteroids
Authors: A. Bewley
Journal: British Journal of Dermatology (2008)

Topical corticosteroids form the mainstay of treatment for many skin conditions. If used appropriately, they are safe and effective, and side-effects are generally uncommon. Current advice to patients to apply topical corticosteroid preparations 'sparingly' or 'thinly' contributes to 'steroid phobia', increasing the risk of poor clinical response and treatment failure. Such cautionary advice also overlooks the fact that the vast majority of patients are prescribed topical corticosteroids of mild potency for which the evidence suggests that the risk of harm is minimal. In the patient's mind, the current advice groups all steroids together regardless of their potential for adverse effects. The advice also tends to reinforce an erroneous concern that the risks from topical corticosteroids may be similar to those from systemic corticosteroids. We propose a change to make the pharmacy labelling of topical corticosteroids more accurately reflect the low risk of harm from corticosteroids of low to moderate potency and the importance of applying sufficient medication to achieve a satisfactory clinical response. This change could provide the focus for updated, evidence-based education for healthcare professionals in prescribing of topical corticosteroids and help in the provision of more appropriate advice to patients. We recommend that patients are informed that treatment should not exceed prescribed quantities, and continuing treatment should be under careful medical supervision. We also recommend that topical corticosteroid products include clear 'fingertip unit' instructions, preferably with images of a 'fingertip unit' and a chart to show the number of units required for specific areas of the body.
Imbalance between Cysteine Proteases and Inhibitors in a Baboon Model of Bronchopulmonary Dysplasia
Authors: Ozden Altiok, Ryuji Yasumatsu, Gulbin Bingol-Karakoc, Richard J. Riese, Mildred T. Stahlman, William Dwyer, Richard A. Pierce, Dieter Bromme, Ekkehard Weber, Sule Cataltepe
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Bronchopulmonary dysplasia (BPD) continues to be a major morbidity in preterm infants. The lung pathology in BPD is characterized by impaired alveolar and capillary development. An imbalance between proteases and protease inhibitors in association with changes in lung elastic fibers has been implicated in the pathogenesis of BPD.
Extrahepatic cholestasis increases liver stiffness (FibroScan) irrespective of fibrosis
Authors: Gunda Millonig, Frank M. Reimann, Stephanie Friedrich, Hamidreza Fonouni, Arianeb Mehrabi, Markus W. Büchler, Helmut Karl Seitz, Sebastian Mueller
Journal: Hepatology (2008)

Abstract Transient elastography (FibroScan [FS]) is a novel non-invasive tool to assess liver fibrosis/cirrhosis. However, it remains to be determined if other liver diseases such as extrahepatic cholestasis interfere with fibrosis assessment because liver stiffness is indirectly measured by the propagation velocity of an ultrasound wave within the liver. In this study, we measured liver stiffness immediately before endoscopic retrograde cholangiopancreatography and 3 to 12 days after successful biliary drainage in patients with extrahepatic cholestasis mostly due to neoplastic invasion of the biliary tree. Initially elevated liver stiffness decreased in 13 of 15 patients after intervention, in 10 of them markedly. In three patients, liver stiffness was elevated to a degree that suggested advanced liver cirrhosis (mean, 15.2 kPa). Successful drainage led to a drop of bilirubin by 2.8 to 9.8 mg/dL whereas liver stiffness almost normalized (mean, 7.1 kPa). In all patients with successful biliary drainage, the decrease of liver stiffness highly correlated with decreasing bilirubin (Spearman's ρ = 0.67, P &lt; 0.05) with a mean decrease of liver stiffness of 1.2 ± 0.56 kPa per 1 g/dL bilirubin. Two patients, in whom liver stiffness did not decrease despite successful biliary drainage, had advanced liver cirrhosis and multiple liver metastases, respectively. The relationship between extrahepatic cholestasis and liver stiffness was reproduced in an animal model of bile duct ligation in landrace pigs where liver stiffness increased from 4.6 kPa to 8.8 kPa during 120 minutes of bile duct ligation and decreased to 6.1 kPa within 30 minutes after decompression. Conclusion: Extrahepatic cholestasis increases liver stiffness irrespective of fibrosis. Once extrahepatic cholestasis is excluded (e.g., by liver imaging and laboratory parameters) transient elastography is a valuable tool to assess liver fibrosis in chronic liver diseases. (Hepatology 2008.)
Effects of Catechol-<i>O</i>-Methyltransferase on Normal Variation in the Cognitive Function of Children
Authors: Jennifer H. Barnett, Jon Heron, David Goldman, Peter B. Jones, Ke Xu
Journal: American Journal of Psychiatry (2009)

Genetic variants that contribute to the risk of psychiatric disorders may also affect normal variation in psychological function. Indeed, the behavioral effects of many genetic variants may be better understood as process-specific rather than disease-specific. A functional valine-to-methionine (Val(158)Met) polymorphism in the catechol-O-methyltransferase (COMT) gene has been associated with cognitive function and brain metabolic activity accompanying such tasks. Not all studies are consistent, and less is known about the effect of this polymorphism during development. The authors tested the hypothesis that a more informative COMT haplotype predicts normal cognitive development in a large population-based cohort of children enrolled in the Avon Longitudinal Study of Parents and Children.
Phase 2 randomized, flexible crossover, double-blinded, placebo-controlled trial of the farnesyltransferase inhibitor tipifarnib in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas
Authors: B. C. Widemann, E. Dombi, A. Gillespie, P. L. Wolters, J. Belasco, S. Goldman, B. R. Korf, J. Solomon, S. Martin, W. Salzer, E. Fox, N. Patronas, M. W. Kieran, J. P. Perentesis, A. Reddy, J. J. Wright, A. Kim, S. M. Steinberg, F. M. Balis
Journal: Neuro-Oncology (2014)

RAS is dysregulated in neurofibromatosis type 1 (NF1) related plexiform neurofibromas (PNs). The activity of tipifarnib, which blocks RAS signaling by inhibiting its farnesylation, was tested in children and young adults with NF1 and progressive PNs.Patients aged 3-25 years with NF1-related PNs and imaging evidence of tumor progression were randomized in a double-blinded fashion to receive tipifarnib (200 mg/m(2) orally every 12 h) or placebo (phase A) and crossed over to the opposite treatment arm at the time of tumor progression (phase B). PN volumes were measured with MRI, and progression was defined as ≥20% volume increase. Time to progression (TTP) in phase A was the primary endpoint, and the trial was powered to detect whether tipifarnib doubled TTP compared with placebo. Toxicity, response, and quality of life were also monitored.Sixty-two patients were enrolled. Tipifarnib and placebo were well tolerated. On phase A, the median TTP was 10.6 months on the placebo arm and 19.2 months on the tipifarnib arm (P = .12; 1-sided). Quality of life improved significantly compared with baseline on the tipifarnib arm but not on the placebo arm. Volumetric tumor measurement detected tumor progression earlier than conventional 2-dimensional (WHO) and 1-dimensional (RECIST) methods.Tipifarnib was well tolerated but did not significantly prolong TTP of PNs compared with placebo. The randomized, flexible crossover design and volumetric PN assessment provided a feasible and efficient means of assessing the efficacy of tipifarnib. The placebo arm serves as an historical control group for phase 2 single-arm trials directed at progressive PNs.
A young boy with deforming arthropathy
Authors: R Handa, P Aggarwal, J P Wali
Journal: Annals of the Rheumatic Diseases (1998)

Case reportA 15 year old boy presented with a three year history of painless swelling of the proximal interphalangeal (PIP) joints of both the hands.The illness started at the age of 12 years without any history of preceding trauma or cold exposure.There was no fever, morning stiVness or pain.There was no limitation of hand functions like writing skills, grasping, etc.However, for the past six months, the patient had noticed flexion deformities of the little fingers, which could not be corrected.No other joints were involved.The patient was one of three children of a non-consanguinous marriage.None of the parents or other siblings had similar illness.The patient had been treated by his doctor for juvenile chronic arthritis with diclofenac sodium and low dose prednisone for six months without any improvement.General physical and systemic examinations were entirely normal.Joint examination showed firm swelling of the PIP joints.No erythema, local rise in temperature or tenderness were noted.The fingers showed flexion deformity.No shortening was apparent.Active and passive movements were normal except in the little fingers, which had a fixed deformity (fig 1 ) .All other joints of the hand and feet were normal.Investigations showed haemoglobin 14.2 g/dl, leucocytes 6.1 × 10 9 /l ( neutrophils 70%, lymphocytes 25%, monocytes 3%, eosinophils 2%) and platelets 300 × 10 9 /l.Westergren erythrocyte sedimentation rate (ESR) was 5 mm 1st h.Rheumatoid factor and antinuclear antibodies were negative.Antistreptolysin O titres were normal.Blood urea nitrogen, serum creatinine, serum proteins, aminotransferases were within normal limits.Urine analysis was normal.Hand radiographs showed irregularity
PANCREATIC TRANSPLANTATIONS IN THE SPLEEN
Authors: Joseph H. Pratt, Fred T. Murphy
Journal: The Journal of Experimental Medicine (1913)

Pancreatic tissue implanted in the spleen and separated from its original vascular and nervous connections can live and functionate for months. A small nodule of pancreatic tissue composed of acini without demonstrable islands of Langerhans prevented the development of diabetes. Death occurred 187 days after the extirpation of the pancreas.
The cost of long term therapy for gastro-oesophageal reflux disease: a randomised trial comparing omeprazole and open antireflux surgery
Authors: H E Myrvold
Journal: Gut (2001)

<h3>BACKGROUND AND AIM</h3> To comprehensively assess the relative merits of medical and surgical therapy for gastro-oesophageal reflux disease (GORD), health economic aspects have to be incorporated. We have studied the direct and indirect costs of medical and surgical therapy within the framework of a prospective randomised multicentre trial. <h3>METHODS</h3> After initial treatment of reflux oesophagitis with omeprazole to control symptoms and to heal oesophagitis, 154 patients were randomised to continue treatment with omeprazole (20 or 40 mg daily) and 144 patients to have an open antireflux operation (ARS). In case of GORD relapse, patients allocated to omeprazole were offered ARS and those initially operated on had either a reoperation or were treated with omeprazole. The costs were assessed over five years from randomisation. <h3>RESULTS</h3> Differences in cumulative direct medical costs per patient between the two therapeutic strategies diminished with time. However, five year direct medical costs per patient when given omeprazole were still significantly lower than for those having ARS in Denmark, Norway, and Sweden (differences were DKK 8703 (US$1475), NOK 32 992 (US$ 5155), and SEK 13 036 (US$ 1946), respectively). However, in Finland the reverse was true (the difference in favour of ARS amounted to FMK 7354 (US$ 1599)). When indirect costs (loss of production due to GORD related sick leave) were also included, the cost of surgical treatment increased substantially and exceeded the cost of medical treatment in all countries. <h3>CONCLUSIONS</h3> The total costs of medical therapy for chronic GORD were lower than those of open ARS when prospectively assessed over a five year period, although significant differences in cost estimates were revealed between countries.
Genetic variants in pre-eclampsia: a meta-analysis
Authors: A.J. Buurma, R.J. Turner, J.H.M. Driessen, A.L. Mooyaart, J.W. Schoones, J.A. Bruijn, K.W.M. Bloemenkamp, O.M. Dekkers, H.J. Baelde
Journal: Human Reproduction Update (2013)

BACKGROUND Pre-eclampsia has a clear familial component, suggesting that the condition may be partly attributable to genetic susceptibility. The search for susceptibility genes has led to a drastic increase in the number of published studies associating genetic factors with pre-eclampsia. However, attempts to replicate these findings have yielded inconsistent results. This meta-analysis assessed the pooled effect of each genetic variant that is reproducibly associated with pre-eclampsia. METHODS Studies that assessed the association between genes and pre-eclampsia were searched in PubMed, Embase and Web of Science. We selected all genetic variants that were significantly associated with pre-eclampsia in an initial study and were subsequently independently reproduced in at least one additional study. All studies that assessed these reproduced variants were then included. The association between genetic variants and pre-eclampsia was calculated at the allele level, and the main measure of effect was a pooled odds ratio in a random-effects model. RESULTS The literature search yielded 2965 articles, of which 542 investigated genetic associations in pre-eclampsia. We identified 22 replicated genetic variants, of which 7 remained significantly associated with pre-eclampsia following meta-analysis. These variants were in or near the following genes: ACE, CTLA4, F2, FV, LPL and SERPINE1. CONCLUSIONS This meta-analysis identified seven genetic variants associated with pre-eclampsia. Importantly, many of these variants are also risk factors for developing cardiovascular disease, revealing that pre-eclampsia and cardiovascular disease have shared genetic risk factors. The contribution of the identified genetic variants in the pathogenesis of pre-eclampsia should be the focus of future studies.
Effective Activity of Cytokine-Induced Killer Cells against Autologous Metastatic Melanoma Including Cells with Stemness Features
Authors: Loretta Gammaitoni, Lidia Giraudo, Valeria Leuci, Maja Todorovic, Giulia Mesiano, Franco Picciotto, Alberto Pisacane, Alessandro Zaccagna, Maria Giuseppa Volpe, Susanna Gallo, Daniela Caravelli, Elena Giacone, Tiziana Venesio, Antonella Balsamo, Ymera Pignochino, Giovanni Grignani, Fabrizio Carnevale-Schianca, Massimo Aglietta, Dario Sangiolo
Journal: Clinical Cancer Research (2013)

We investigate the unknown tumor-killing activity of cytokine-induced killer (CIK) cells against autologous metastatic melanoma and the elusive subset of putative cancer stem cells (mCSC).We developed a preclinical autologous model using same patient-generated CIK cells and tumor targets to consider the unique biology of each patient/tumor pairing. In primary tumor cell cultures, we visualized and immunophenotypically defined a putative mCSC subset using a novel gene transfer strategy that exploited their exclusive ability to activate the promoter of stemness gene Oct4.The CIK cells from 10 patients with metastatic melanoma were successfully expanded (median, 23-fold; range, 11-117). Primary tumor cell cultures established and characterized from the same patients were used as autologous targets. Patient-derived CIK cells efficiently killed autologous metastatic melanoma [up to 71% specific killing (n = 26)]. CIK cells were active in vivo against autologous melanoma, resulting in delayed tumor growth, increased necrotic areas, and lymphocyte infiltration at tumor sites. The metastatic melanoma cultures presented an average of 11.5% ± 2.5% putative mCSCs, which was assessed by Oct4 promoter activity and stemness marker expression (Oct4, ABCG2, ALDH, MITF). Expression was confirmed on mCSC target molecules recognized by CIK cells (MIC A/B; ULBPs). CIK tumor killing activity against mCSCs was intense (up to 71%, n = 4) and comparable with results reported against differentiated metastatic melanoma cells (P = 0.8).For the first time, the intense killing activity of CIK cells against autologous metastatic melanoma, including mCSCs, has been shown. These findings move clinical investigation of a new immunotherapy for metastatic melanoma, including mCSCs, closer.