tbuckley/cabot-search huggingface dataset:
Dissection of human humoral immune response against hepatitis C virus E2 glycoprotein by repertoire cloning and generation of recombinant fab fragments
Authors: Roberto Burioni, Paola Plaisant, Aldo Manzin, Domenico Rosa, Valeria Delli Carri, Francesca Bugli, Laura Solforosi, Sergio Abrignani, Pietro E. Varaldo, Giovanni Fadda, Massimo Clementi
Journal: Hepatology (1998)

Demonstration of antibodies inhibiting key viral functions is the basis for the design of an effective vaccine. Dissection of the human antibody response by repertoire cloning may be a powerful means to address this issue. In this study, a panel of human monoclonal recombinant Fab fragments specific for hepatitis C virus (HCV) E2 envelope protein was generated. The selection procedure was designed to select for cross-genotype reactive antibodies. Sequences coding five different human recombinant Fabs specific for the HCV/E2 protein were cloned and characterized. The ability of the cloned antibody fragments to inhibit adhesion of recombinant envelope E2 protein to target cells was assayed. While affinity of the different antibody fragments appeared similar, activity in inhibiting E2 binding to target cells varied considerably from one Fab fragment to another. Two Fabs were not able to inhibit E2 binding at high concentration (40 microg/mL), while three other Fab clones were active in neutralizing 50% of the E2 binding at concentrations ranging from 3 to 0.35 microg/mL.
Recent Advances in Treatment of Gonorrhoea
Authors: D. J. Mackinnon
Journal: BMJ (1940)

Before considering the effects of adjuvant sulphonamide therapy it is of advantage to recall the position before the introduction of these drugs.Since, also, the object of treatment is to attain cure as rapidly as possible, it is necessary to show to what extent the period of time taken has been shortened, first, with the introduction of uleron, and, later, of sulphapyridine (M & B 693).
New Frontiers in the Study of Amyloidosis
Authors: Alan S. Cohen, Martha Skinner
Journal: New England Journal of Medicine (1990)

Twenty-three years ago, when an extensive review of amyloidosis was published in the Journal, the disease was still regarded as very rare.1 In a lifetime of practice, a physician might see one case. The condition was also poorly understood. Over the past 30 years, however, research on amyloidosis has rapidly come of age. The amyloid fibril has been found to consist of one of many different proteins, some relating to immunoglobulin light chains (AL) and some relating to the newly described protein amyloid A (AA), with its precursor, serum amyloid A, soon identified as an apolipoprotein. The list of . . .
Significant improvement in the survival of patients with multiple myeloma presenting with severe renal impairment after the introduction of novel agents
Authors: M.A. Dimopoulos, S. Delimpasi, E. Katodritou, A. Vassou, M.C. Kyrtsonis, P. Repousis, Z. Kartasis, A. Parcharidou, M. Michael, E. Michalis, D. Gika, A. Symeonidis, A. Pouli, K. Konstantopoulos, E. Terpos, E. Kastritis
Journal: Annals of Oncology (2013)
Epicardium-Derived Cells in Development of Annulus Fibrosis and Persistence of Accessory Pathways
Authors: Denise P. Kolditz, Maurits C.E.F. Wijffels, Nico A. Blom, Arnoud van der Laarse, Nathan D. Hahurij, Heleen Lie-Venema, Roger R. Markwald, Robert E. Poelmann, Martin J. Schalij, Adriana C. Gittenberger-de Groot
Journal: Circulation (2008)

The developmental mechanisms underlying the persistence of myocardial accessory atrioventricular pathways (APs) that bypass the annulus fibrosis are mainly unknown. In the present study, we investigated the role of epicardium-derived cells (EPDCs) in annulus fibrosis formation and the occurrence of APs.EPDC migration was mechanically inhibited by in ovo microsurgery in quail embryos. In ovo ECGs were recorded in wild-type (n=12) and EPDC-inhibited (n=12) hearts at Hamburger-Hamilton (HH) stages 38 to 42. Subsequently, in these EPDC-inhibited hearts (n=12) and in additional wild-type hearts (n=45; HH 38-42), ex ovo extracellular electrograms were recorded. Electrophysiological data were correlated with differentiation markers for cardiomyocytes (MLC2a) and fibroblasts (periostin). In ovo ECGs showed significantly shorter PR intervals in EPDC-inhibited hearts (45+/-10 ms) than in wild-type hearts (55+/-8 ms, 95% CI 50 to 60 ms, P=0.030), whereas the QRS durations were significantly longer in EPDC-inhibited hearts (29+/-14 versus 19+/-2 ms, 95% CI 18 to 21 ms, P=0.011). Furthermore, ex ovo extracellular electrograms (HH 38-42) displayed base-first ventricular activation in 44% (20/45) of wild-type hearts, whereas in all EPDC-inhibited hearts (100%, 12/12), the ventricular base was activated first (P<0.001). Small periostin- and MLC2a-positive APs were found mainly in the posteroseptal region of both wild-type and EPDC-inhibited hearts. Interestingly, in all (n=10) EPDC-inhibited hearts, additional large periostin-negative and MLC2a-positive APs were found in the right and left lateral free wall coursing through marked isolation defects in the annulus fibrosis until the last stages of embryonic development.EPDCs play an important role in annulus fibrosis formation. EPDC outgrowth inhibition may result in marked defects in the fibrous annulus with persistence of large APs, which results in ventricular preexcitation on ECG. These APs may provide a substrate for postnatally persistent reentrant arrhythmias.
BCL6 Controls the Expression of the B7-1/CD80 Costimulatory Receptor in Germinal Center B Cells
Authors: Huifeng Niu, Giorgio Cattoretti, Riccardo Dalla-Favera
Journal: The Journal of Experimental Medicine (2003)

The BCL6 proto-oncogene encodes a transcriptional repressor required for the development of germinal centers (GCs) and implicated in the pathogenesis of GC-derived B cell lymphoma. Understanding the precise role of BCL6 in normal GC formation and in lymphomagenesis depends on the identification of genes that are direct targets of its transcriptional repression. Here we report that BCL6 directly controls the expression of B7–1/CD80, a costimulatory receptor involved in B–T cell interactions critical for the development of T cell–mediated antibody responses. Upon CD40 signaling, transcription of the CD80 gene is induced by the nuclear factor (NF)-κB transcription factor. Our results show that BCL6 prevents CD40-induced expression of CD80 by binding its promoter region in vivo and suppressing its transcriptional activation by NF-κB. Consistent with a physiologic role for BCL6 in suppressing CD80, the expression of these two genes is mutually exclusive in B cells, and BCL6-defective mice show increased expression of CD80 in B cells. The results suggest that BCL6 may directly control the ability of B cell to interact with T cells during normal GC development. In addition, these findings imply that T–B cell interactions may be disrupted in B cell lymphoma expressing deregulated BCL6 genes.
Patient's charter in outpatient services.
Authors: C. G. Kelly
Journal: BMJ (1992)

consent, as they move within the NHS, house officers may be unaware that they are not protected against prescribed diseases such as tuberculosis and hepatitis B. It may well be that Lewisham Hospital's handbook mentions the occupational health department.Luisa Dillner's review of Stress and the Medical Profession seems to confirm my views.2The pen- ultimate paragraph suggests that doctors need an accessible counselling service and an occupational health service that is geared to recognising stress.The standard and quality of occupational health services vary considerably within the NHS, but it is essential that all staff, including doctors, become more aware of the services they offer.
Oral Activated Charcoal to Enhance Theophylline Elimination in an Acute Overdose
Authors: Peter Gal
Journal: JAMA (1984)

HEMODIALYSIS 1 or charcoal hemoperfusion 2 is often thought to be required when patients overdose with a near-lethal quantity of toxic drugs. 2 Recently, however, oral charcoal has been investigated as a noninvasive means of enhancing drug removal from the blood, 3-8 referred to by Levy 3 as gastrointestinal dialysis. We report a case of theophylline overdose in which oral activated charcoal was used to promote theophylline removal from the body.  Report of a Case  A 23-year-old woman complained of symptoms of nausea, vomiting, diarrhea, tachycardia, and extreme tremulousness; allegedly she had taken twenty 5-mg tablets of terbutaline sulfate and twenty 200-mg tablets of theophylline (Theo-dur) in a suicide gesture earlier that day. In the emergency room, several theophylline and terbutaline tablets were found in the vomitus. Her serum theophylline concentration at the time of admission was 32.5 mg/L, rising to a peak of 98.7 mg/L shortly thereafter. Eighteen hours
Activation of the PI3 Kinase Pathway By Retinoic Acid Mediates Sodium/Iodide Symporter Induction and Iodide Transport in MCF-7 Breast Cancer Cells
Authors: Emi Ohashi, Takahiko Kogai, Hiroyuki Kagechika, Gregory A. Brent
Journal: Cancer Research (2009)

Abstract Iodide uptake in the thyroid and breast is mediated by the sodium/iodide symporter (NIS). NIS activation is used for radioiodide imaging and therapeutic ablation of thyroid carcinoma. NIS is expressed in &amp;gt;70% of breast cancers but at a level insufficient for radioiodine treatment. All-trans retinoic acid (tRA) induces NIS gene expression and functional iodide uptake in human breast cancer cell lines and mouse breast cancer models. tRA usually regulates gene expression by direct interaction of RA receptor (RAR) with a target gene, but it can also act through nongenomic pathways. We report a direct influence of tRA treatment on the phosphoinositide 3-kinase (PI3K) signal transduction pathway that mediates tRA-induced NIS expression in MCF-7 breast cancer cells. MCF-7 cells express all three RAR isoforms, α, β, and γ, and RXRα. We previously identified RARβ and RXRα as important for NIS induction by tRA. Treatment with LY294002, the PI3K inhibitor, or p85α knockdown with siRNA abolished tRA-induced NIS expression. Immunoprecipitation experiments and glutathione S-transferase pull-down assay showed a direct interaction between RARβ2, RXRα, and p85α. RA also induced rapid activation of Akt in MCF-7 cells. Treatment with an Akt inhibitor or Akt knockdown with siRNA reduced NIS expression. These findings indicate that RA induction of NIS in MCF-7 cells is mediated by rapid activation of the PI3K pathway and involves direct interaction with RAR and retinoid X receptor. Defining these mechanisms should lead to methods to further enhance NIS expression, as well as retinoid targets that influence growth and differentiation of breast cancer. [Cancer Res 2009;69(8):3443–50]
Skeletonized Internal Thoracic Artery Harvest Reduces Pain and Dysesthesia and Improves Sternal Perfusion After Coronary Artery Bypass Surgery
Authors: Munir Boodhwani, B. Khanh Lam, Howard J. Nathan, Thierry G. Mesana, Marc Ruel, Wanzhen Zeng, Frank W. Sellke, Fraser D. Rubens
Journal: Circulation (2006)

Observational studies suggest that skeletonization of the internal thoracic artery (ITA) can improve conduit flow and length and reduce deep sternal infections and postoperative pain. We performed a randomized, double-blind, within-patient comparison of skeletonized and nonskeletonized ITAs in patients undergoing coronary surgery.Patients (n = 48) undergoing bilateral ITA harvest were randomized to receive 1 skeletonized and 1 nonskeletonized ITA. Intraoperatively, ITA flow was assessed directly and with a Doppler flow probe before and after topical application of papaverine. ITA harvest time and conduit length were recorded. A blinded assessment of pain (visual analog scale) and dysesthesia (physical examination) was performed at discharge, at 2 weeks, and at a 3-month follow-up. Sternal perfusion was assessed with nuclear imaging (n = 7). Skeletonization required longer ITA harvest times (27 +/- 1 versus 24 +/- 1 minutes; P = 0.04). There was a trend toward increased ITA length in the skeletonized group (18.2 +/- 0.3 versus 17.7 +/- 0.3 cm; P = 0.09). In situ ITA flow was lower in skeletonized arteries (7.4 +/- 0.9 versus 10.1 +/- 1.0 mL/min; P = 0.01) and increased significantly after ITA division and papaverine application. Postanastomotic flows were similar between groups. Skeletonization was associated with decreased pain at the 3-month follow-up and a reduction in major sensory deficits at the 4-week and 3-month (17% versus 50%; P = 0.002) follow-ups. Baseline adjusted sternal perfusion was significantly greater by 17 +/- 6% (P = 0.03) on the skeletonized side.Skeletonization results in reduced postoperative pain and dysesthesia and increased sternal perfusion at follow-up but does not produce increased conduit flow. ITA skeletonization may be a strategy for reducing morbidity after CABG.
Fasting Plasma Glucose as a Screening Test for Diabetes and Its Relationship With Cardiovascular Risk Factors in Hong Kong Chinese
Authors: Gary TC Ko, Juliana CN Chan, Edith Lau, Jean Woo, Clive S Cockram
Journal: Diabetes Care (1997)

OBJECTIVE To evaluate the use of fasting plasma glucose (FPG) in the diagnosis of diabetes and the relationship between FPG and various cardiovascular risk factors in a community-based Hong Kong Chinese population. RESEARCH DESIGN AND METHODS The results of 1,470 oral glucose tolerance tests from a prevalence survey for glucose intolerance and lipid abnormality in a Hong Kong Chinese working population were examined. Our previous report showed that an FPG of 5.7 mmol/l corresponded to a 2-h plasma glucose (PG) of 11.1 mmol/l, and we used this value as a cutoff value and examined the relationship between FPG and various cardiovascular risk factors in nondiabetic subjects. RESULTS An FPG cutoff value of 7.8 mmol/l gave a sensitivity of 20.0% and a specificity of 100% in the diagnosis of diabetes (defined as 2-h PG ≥ 11.1 mmol/l). We divided the non-diabetic subjects (FPG &amp;lt; 7.8 mmol/l and 2-h PG &amp;lt; 11.1 mmol/l) into two groups: subjects with FPG &amp;lt; 5.7 mmol/l and those with FPG ≥ 5.7 mmol/l and &amp;lt; 7.8 mmol/l. Subjects in the latter group were older, had higher blood pressure, BMI, waist-to-hip ratio, 2-h PG, fasting and 2-h insulin, fasting serum triglyceride, VLDL cholesterol, apolipoprotein B, and urinary albumin concentrations, as well as lower plasma HDL cholesterol and HDL2 cholesterol concentrations. CONCLUSIONS These findings suggest that an FPG cutoff value of 7.8 mmol/l, as recommended by the World Health Organization, was too high when applied to Chinese populations. As in the case of hyperlipidemia, plasma glucose concentration should be viewed as a continuum in terms of its relationship with cardiovascular risk.
CD4-Positive T-Lymphocytes Infiltrate the Bronchial Mucosa of Patients with Sjögren's Syndrome
Authors: SPYROS A. PAPIRIS, MARINA SAETTA, GRAZIELLA TURATO, RENATO LA CORTE, LUCIO TREVISANI, CRISTINA E. MAPP, PIERO MAESTRELLI, LEONARDO M. FABBRI, ALFREDO POTENA
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

To investigate the degree and the type of inflammation in the bronchial mucosa in patients with Sjögren's syndrome, we examined lobar bronchial biopsies obtained from 10 patients with Sjögren's syndrome (six with primary and four with secondary) and eight control subjects. Histochemistry with hematoxylin-eosin was performed both to identify the number of mononuclear cells and eosinophils and to measure the thickness of the basement membrane. Immunohistochemistry was performed to identify neutrophils (neutrophil-elastase), macrophages (CD68), and T-lymphocyte subpopulations (CD4 and CD8) in the submucosa. Subjects with Sjögren's syndrome presented a greater number of CD4-positive T-lymphocytes than did the normal control subjects (p = 0.0129). Instead, eosinophils, neutrophils, macrophages, CD8 positive T-lymphocytes, and basement membrane thickness were similar in the two groups. There were no differences in cell counts between patients with primary and those with secondary Sjögren's syndrome and between symptomatic and asymptomatic patients. No correlation was found between cell counts, symptoms, lung volumes, and disease duration. This study has shown that patients with Sjögren's syndrome have an increased number of CD4 positive T-lymphocytes in the bronchial mucosa outside of the bronchial glands, supporting the concept that, in the airways, Sjögren's syndrome involves also extraglandular tissues.
Evaluation of Protocol Before Transplantation and After Reperfusion Biopsies From Human Orthotopic Liver Allografts: Considerations of Preservation and Early Immunological Injury
Authors: Saburo Kakizoe, Katsuhiko Yanaga, Thomas E. Starzl, Jake A. Demetris
Journal: Hepatology (1990)

Light microscopic, immunohistochemical and ultrastructural analysis of protocol before transplantation and after reperfusion biopsy specimens from 87 randomly selected patients was performed to assess the contribution of preservation and immunological injury to early graft failure. Most biopsy specimens were essentially normal by light microscopy before transplantation, and no particular feature could be relied on to predict function after transplantation. Ultrastructural examination of biopsy specimens before transplantation demonstrated preferential degeneration of sinusoidal lining cells, but no strict correlation was seen between ultrastructural sinusoidal integrity before transplantation and function after transplantation. The presence of zonal or severe focal necrosis and a severe neutrophilic exudate in biopsy specimens after reperfusion presaged a poor early postoperative course in most, but not all, patients. The presence of preformed lymphocytotoxic antibodies had no effect on the early clinical course, but was associated with Kupffer cell hypertrophy in needle biopsy specimens taken after transplantation. No definite evidence was seen of hyperacute rejection as a result of preformed lymphocytotoxic antibodies as detected in conventional assays. These findings suggest that preservation injury accounts for only a subset of grafts that fail to function after transplantation. Other perioperative or "recipient" factors may be of equal or greater importance in early graft dysfunction or failure.
Errors in Diagnosis
Authors: L. Sheldon
Journal: BMJ (1947)

<h3>ABSTRACT</h3> The close association between astrocytes and microglia causes great difficulties to distinguish their individual roles in innate immune responses in central nervous system. Current chemical-based methods to eliminate microglia in glial cell culture introduce various molecular and functional alterations to astrocytes. Here, we describe a novel two-step approach to achieve a complete elimination of microglia without affecting the biological properties of co-cultured astrocytes by temporal treatment of histone deacetylase inhibitor trichostatin A (TSA). We verify TSA as a potent inducer for microglial-specific cell death, which also causes comprehensive gene expression changes in astrocytes. However, withdrawal of TSA not only ensures no microglia repopulation, but also restores all the gene expression changes in terms of astrocyte functions, including neurotrophic factors, glutamate and potassium transporters, and reactive astrocyte subtypes. By contrast, withdrawal of PLX5622, the commonly used colony-stimulating factor 1 receptor inhibitor neither prevents microglia repopulation nor restores the gene expression changes mentioned above. Using this method, we are able to discriminate differential roles of microglia and astrocytes in the induced expression of antiviral and pro-inflammatory cytokines upon various pathological stimuli including the spike protein of SARS-CoV-2. This simple and efficient method can be customized for the understanding of microglia-astrocyte interaction and the development of epigenetic therapies that target over-activated microglia in neuroinflammation-related diseases.
Nursing Education and Nursing Service
Authors: Dorothy M. Smith
Journal: JAMA (1965)

Teaching hospitals are an integral part of the education of medical students and of the continuing education of medical faculty and practitioners. A medical hierarchy in the functional structure of the teaching hospital, based on knowledge and skill in dealing with the medical problems of patients, includes the various levels of house staff, the medical students, and the clinical medical faculty. These form a cohesive learning-teaching service group and apply knowledge and skill to solving of patients' medical problems. Staff, students, and faculty ask questions of one another. They are scientific investigators— some with much knowledge and skill, some with little. It is not always as obvious, however, that a teaching hospital is a place where investigation in nursing is going on—where each patient's nursing problems are investigated, questioned, and studied by a similar nursing hierarchy of students, clinical faculty, and house staff. More frequently, the faculty, not always expert
The influence of aging and growth on the postnatal development of cardiac muscle in rats.
Authors: K Rakusan, S Raman, R Layberry, B Korecky
Journal: Circulation Research (1978)

We studied the effects of different rates of postnatal body growth on the growth of rat myocytes.Growth rates were altered by adjusting the number of newborn animals per litter to 4 (fast-growing), 8 (normal), or 16 (slow-growing).On the 21st postnatal day, average left ventricular weights (mg ± SEM) were 80 ± 5 in slowgrowing 131 ± 8 in normal, and 183 ± 5 in fast-growing rats.Average myocyte diameters, obtained from direct microscopic measurements in longitudinal sections prepared from eight animals in each group, were 8.6 ± 0.3, 9.8 ± 0.2, and 10.2 ± 0.3 fim, respectively.The total number and total length of myocytes constituting the left ventricle were estimated, assuming a constant length-to-width ratio and cyclindrical model of myocytes.The estimated total number of myocytes constituting the respective left ventricles were 23.6 ± 2.0, 24.5 ± 2.2, and 31.1 ± 2.1 millions.All differences between experimental groups were significant by analysis of variance.When the estimated total numbers of myocytes and their estimated total lengths were related to the left ventricular weights, a significant linear correlation was obtained, which indicated their dependence on the organ growth and their relative independence of age.These indications were strengthened further by analysis of covariance, which showed that the differences in all morphometric data among the three groups of hearts may be explained entirely by different growth rates of the left ventricle.These results also suggest that the accelerated growth of the heart during the early postnatal period is associated with increased proliferation of myocytes.