tbuckley/cabot-search huggingface dataset:
Targeted Cell Entry of Lentiviral Vectors
Authors: Sabrina Funke, Andrea Maisner, Michael D Mühlebach, Ulrike Koehl, Manuel Grez, Roberto Cattaneo, Klaus Cichutek, Christian J Buchholz
Journal: Molecular Therapy (2008)

Retargeting of lentiviral vector entry to cell types of interest is a key factor in improving the safety and efficacy of gene transfer. In this study we show that the retargetable envelope glycoproteins of measles virus (MV), namely, the hemagglutinin (H) responsible for receptor recognition and the fusion protein (F), can pseudotype human immunodeficiency virus 1 (HIV-1) vectors when their cytoplasmic tails are truncated. We then pseudotyped HIV-1 vectors with MV glycoproteins displaying on H either the epidermal growth factor or a single-chain antibody directed against CD20, but without the ability to recognize their native receptors. Gene transfer into cells that expressed the targeted receptor was several orders of magnitude more efficient than into cells that did not. High-target versus nontarget cell discrimination was demonstrated in mixed cell populations, where the targeting vector selectively eliminated CD20-positive cells after suicide gene transfer. Remarkably, primary human CD20-positive B lymphocytes were transduced more efficiently by the CD20-targeted vector than by a vector pseudotyped with the vesicular stomatitis virus G (VSV-G) protein. In addition, the CD20-targeted vector was able to transduce even unstimulated primary B cells, whereas VSV-G pseudotyped vectors were unable to do so. Because MV enters cells through direct fusion at the cell membrane, this novel targeting system should be widely applicable. Retargeting of lentiviral vector entry to cell types of interest is a key factor in improving the safety and efficacy of gene transfer. In this study we show that the retargetable envelope glycoproteins of measles virus (MV), namely, the hemagglutinin (H) responsible for receptor recognition and the fusion protein (F), can pseudotype human immunodeficiency virus 1 (HIV-1) vectors when their cytoplasmic tails are truncated. We then pseudotyped HIV-1 vectors with MV glycoproteins displaying on H either the epidermal growth factor or a single-chain antibody directed against CD20, but without the ability to recognize their native receptors. Gene transfer into cells that expressed the targeted receptor was several orders of magnitude more efficient than into cells that did not. High-target versus nontarget cell discrimination was demonstrated in mixed cell populations, where the targeting vector selectively eliminated CD20-positive cells after suicide gene transfer. Remarkably, primary human CD20-positive B lymphocytes were transduced more efficiently by the CD20-targeted vector than by a vector pseudotyped with the vesicular stomatitis virus G (VSV-G) protein. In addition, the CD20-targeted vector was able to transduce even unstimulated primary B cells, whereas VSV-G pseudotyped vectors were unable to do so. Because MV enters cells through direct fusion at the cell membrane, this novel targeting system should be widely applicable.
Modulation of amyloid β protein precursor processing as a means of retarding progression of Alzheimer’s disease
Authors: Steven L. Wagner, Benito Munoz
Journal: Journal of Clinical Investigation (1999)

Alzheimer’s disease (AD), a chronic neurodegenerative disorder, is characterized neuropathologically by an abundance of extracellular neuritic plaques (NPs) containing large amounts of a predominantly fibrillar peptide termed amyloid β (Aβ). The brains of victims of AD also harbor excessive numbers of neurofibrillary tangles (NFTs). NFTs are intraneuronal accumulations of paired helical filaments composed primarily of hyperphosphorylated isoforms of the microtubule-associated protein tau. In the United States, a definitive diagnosis of AD is based, at autopsy, on histopathological evidence of high numbers of both NPs and NFTs in individuals having a previous clinical history of progressive dementia. Additional neuropathological changes typically accompanying AD include congophilic angiopathy (Aβ fibrils within the basement membrane of the cerebrovasculature) and selective neuronal cell loss.
Evidence of mast-cell activation in a subset of patients with eosinophilic chronic obstructive pulmonary disease
Authors: R.E. Louis, D. Cataldo, M.G. Buckley, J. Sele, M. Henket, L.C. Lau, P. Bartsch, A.F. Walls, R. Djukanovic
Journal: European Respiratory Journal (2002)

Although asthma has been viewed mainly as an eosinophilic disease, and chronic obstructive pulmonary disease (COPD) as a neutrophilic disease, recent studies have shown increased neutrophil counts in severe asthma and sputum eosinophilia in some COPD patients. In an attempt to further characterise these two syndromes according to pathology, the current authors have conducted a study of induced sputum in 15 subjects with COPD, 17 asthmatics, and 17 nonatopic healthy individuals. Sputum was analysed for cytology and levels of eosinophil cationic protein (ECP), albumin, tryptase and soluble intercellular adhesion molecule‐1. The COPD subjects differed from the asthmatics as they had higher sputum neutrophil and lower columnar epithelial cell counts, but there were no differences in any soluble marker studied. When compared to control subjects, both the asthmatic and COPD subjects had raised eosinophil counts and ECP levels. In a subset of COPD subjects with sputum eosinophilia (&gt;3% of total cells), significantly increased levels of tryptase were detected. In conclusion, although chronic obstructive pulmonary disease is a more neutrophilic disease than asthma, the two diseases are difficult to distinguish on the basis of sputum levels of the soluble markers traditionally associated with asthma. However, a subset of patients with chronic obstructive pulmonary disease with airway eosinophilia and mast-cell activation might represent a distinct pathological phenotype.
Onset and Persistence of Postpartum Depression in an Inner-City Maternal Health Clinic System
Authors: Kimberly A. Yonkers, Susan M. Ramin, A. John Rush, Carlos A. Navarrete, Thomas Carmody, Dana March, Stephen F. Heartwell, Kenneth J. Leveno
Journal: American Journal of Psychiatry (2001)

Postpartum depressive disorders lead to maternal disability and disturbed mother-infant relationships, but information regarding the rates of major depressive disorder in minority women is noticeably lacking. The goal of this study was to determine whether the risk factors for and rate of postpartum major depressive disorder in a predominantly African American and Hispanic clinic population would be similar to those reported for Caucasian women.Investigators systematically screened all women scheduled for their first postpartum visit on selected days at four publicly funded inner-city community maternal health clinics in Dallas County (N=802). A multistage screening process included the Edinburgh Postnatal Depression Scale, the Inventory of Depressive Symptomatology, and the Structured Clinical Interview for DSM-IV for a maximum of three assessments during the initial 3-5-week postpartum period.The estimated rate of major depressive disorder during the postpartum period among women in this setting was between 6.5% and 8.5%. Only 50% of the depressed women reported onset following birth. Bottle-feeding and not living with one's spouse or significant other were associated with depression at the first evaluation; persistent depressive symptoms were linked with the presence of other young children at home. Greater severity of depressive symptoms at first contact predicted major depressive disorder several weeks later.Rates of postpartum depression among Latina and African American postpartum women are similar to epidemiologic rates for Caucasian postpartum and nonpostpartum women. As previously shown for Caucasian women, major depressive disorder in many Latina and African American postpartum women begins before delivery, revealing the need to screen pregnant women for depression.
Toxic epidermal necrolysis associated with pentazocine therapy and severe reversible renal failure
Authors: JOHN A. A. HUNTER, ALEX M. DAVISON
Journal: British Journal of Dermatology (1973)

Journal Article Toxic epidermal necrolysis associated with pentazocine therapy and severe reversible renal failure Get access JOHN A. A. HUNTER, JOHN A. A. HUNTER Department of Dermatology, University of Edinburgh and Medical Renal Unit, The Royal Infirmary, Edinburgh Search for other works by this author on: Oxford Academic Google Scholar ALEX M. DAVISON ALEX M. DAVISON Department of Dermatology, University of Edinburgh and Medical Renal Unit, The Royal Infirmary, Edinburgh Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 88, Issue 3, 1 March 1973, Pages 287–290, https://doi.org/10.1111/j.1365-2133.1973.tb07550.x Published: 01 March 1973 Article history Accepted: 31 August 1972 Published: 01 March 1973
VISTA Regulates the Development of Protective Antitumor Immunity
Authors: Isabelle Le Mercier, Wenna Chen, Janet L. Lines, Maria Day, Jiannan Li, Petra Sergent, Randolph J. Noelle, Li Wang
Journal: Cancer Research (2014)

Abstract V-domain Ig suppressor of T-cell activation (VISTA) is a novel negative checkpoint ligand that is homologous to PD-L1 and suppresses T-cell activation. This study demonstrates the multiple mechanisms whereby VISTA relieves negative regulation by hematopoietic cells and enhances protective antitumor immunity. VISTA is highly expressed on myeloid cells and Foxp3+CD4+ regulatory cells, but not on tumor cells within the tumor microenvironment (TME). VISTA monoclonal antibody (mAb) treatment increased the number of tumor-specific T cells in the periphery and enhanced the infiltration, proliferation, and effector function of tumor-reactive T cells within the TME. VISTA blockade altered the suppressive feature of the TME by decreasing the presence of monocytic myeloid-derived suppressor cells and increasing the presence of activated dendritic cells within the tumor microenvironment. In addition, VISTA blockade impaired the suppressive function and reduced the emergence of tumor-specific Foxp3+CD4+ regulatory T cells. Consequently, VISTA mAb administration as a monotherapy significantly suppressed the growth of both transplantable and inducible melanoma. Initial studies explored a combinatorial regimen using VISTA blockade and a peptide-based cancer vaccine with TLR agonists as adjuvants. VISTA blockade synergized with the vaccine to effectively impair the growth of established tumors. Our study therefore establishes a foundation for designing VISTA-targeted approaches either as a monotherapy or in combination with additional immune-targeted strategies for cancer immunotherapy. Cancer Res; 74(7); 1933–44. ©2014 AACR.
Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial
Authors: Arunee Sabchareon, Derek Wallace, Chukiat Sirivichayakul, Kriengsak Limkittikul, Pornthep Chanthavanich, Saravudh Suvannadabba, Vithaya Jiwariyavej, Wut Dulyachai, Krisana Pengsaa, T Anh Wartel, Annick Moureau, Melanie Saville, Alain Bouckenooghe, Simonetta Viviani, Nadia G Tornieporth, Jean Lang
Journal: The Lancet (2012)
Acute bacterial infection in kwashiorkor and marasmus.
Authors: I. Phillips, B. Wharton
Journal: BMJ (1968)

God cast down on them great tribulation, famine, and pesti lence: the people perished. So Hesiod (c. 700 B.c.) described the association between famine and pestilence, and they have been firmly coupled in men's minds at least since that time. McCance (1951) has reviewed the historical association. Children with kwashiorkor or nutritional marasmus often have acute bacterial infections. This has been established mainly by post-mortem surveys. Campbell (1956) found at necropsy microscopical evidence of pyaemic abscesses or bronchopneumo in the lungs of 31 out of 40 malnourished children in Cape Town, and another six had evidence of renal infection. Renal lesions, many of them infective, were also found in two-thirds of a Jamaican series (Stirling, 1962), and Brown (1965) found a 45% incidence ofbronchopneumonia among malnourished infants in a survey of all paediatric necropsies performed over a 12-year period in Mulago Hpspital, Kampala. In Cape Town two clical studies with bacterio logical support attributed many of the deaths to infection of the gut and to generalized septica (Smythe, 1958; Smythe ani Campbell, 1959). Usually, interest has been centred on one or more particular syste, and few attempts have been made to define the geeral pattern of bacterial infection. Since it has been generally assumed that acute bacterial infec tion is common and serious, antibiotics have often been advised in the treatment of all cases of kwashiorkor and marasmus ; but there is little agreement on the most suitable regimen. Peni cillin is widely used (Bhr, Viteri, and Scrimshaw, 1957; Piburn, 1960; de Silva, 1964), sometimes with streptomycin (Dean and Swanne, 1963) or sulphadiazine (Hansen, 1961). Tetracycline is favoured in Jamaica (Garrow, Picou, and Water low, 1962), and Dean (1965) often used chloramphenical. The studies in Cape Town (Smythe, 1958) led to the use of a com bination of chloramphenicol, neomycin, and nystatin, sometimes followed by penicillin and streptomycin and later by yoghurt. During most of 1966 all children admitted to the Medical Research Council Infantile Malniutrition Research Unit, Kam pala, received a five-day course of penicillin. Despite this, pyrexias often of unknown origin were common, tetracycline had frequently to be given later to control chest infections, and a few of the children showed signs of bacteraemic shock (Whar ton, 1966). Finally, the records of the unit showed that, despite all these antibiotics, bronchopneumonia was commonly found at necropsy (Dean, 1965). These clinical difficulties and the lack of agreement on therapy led us to study the pattern of acute bacterial infection in mal nourished children in Kampala.
Effect of Losartan on Microalbuminuria in Normotensive Patients with Type 2 Diabetes Mellitus
Authors: Adrienne A.M. Zandbergen, Marinus G.A. Baggen, Steven W.J. Lamberts, Aart H. Bootsma, Dick de Zeeuw, Rob J.Th. Ouwendijk
Journal: Annals of Internal Medicine (2003)

Background: Angiotensin-converting enzyme inhibitors have shown antiproteinuric effects in normotensive and hypertensive diabetic patients. Angiotensin-receptor antagonists reduce urinary albumin excretion and the risk for renal and cardiovascular complications in hypertensive patients with type 2 diabetes mellitus. The effect of angiotensin-receptor antagonists in normotensive diabetic patients with microalbuminuria has not yet been reported. Objective: To assess the antiproteinuric effects of losartan in normotensive patients with type 2 diabetes and microalbuminuria. Design: Multicenter randomized, double-blind, placebo-controlled clinical trial. Setting: 19 outpatient clinics in the Netherlands. Patients: 147 normotensive patients with type 2 diabetes mellitus and microalbuminuria. Intervention: 74 patients were randomly assigned to receive losartan and 73 patients were assigned to receive placebo for 10 weeks; 71 patients in each group completed the study. The losartan dose was 50 mg during the first 5 weeks and 100 mg during the subsequent 5 weeks. Measurements: Change in urinary albumin excretion rate after 5 and 10 weeks, change in creatinine clearance and blood pressure, and safety and tolerability of losartan. Results: A significant 25% relative reduction in the albumin excretion rate occurred after 5 weeks of the 50-mg losartan dose, with further improvement over the subsequent 5 weeks with the 100-mg dose (relative reduction, 34%). In the losartan group, creatinine clearance did not improve and blood pressure decreased slightly. Side effects did not differ between treatment groups. Conclusions: The angiotensin-receptor antagonist losartan reduces urinary albumin excretion in normotensive patients with type 2 diabetes and microalbuminuria. In multivariate analysis, the antiproteinuric effect of losartan was independent of the associated reduction in blood pressure. Losartan was safe and well tolerated in these normotensive patients.
The Nature of Fibrositis: I. The Myalgic Lesion and its Secondary Effects: a Reflex Theory
Authors: Michael Kelly
Journal: Annals of the Rheumatic Diseases (1945)

The monoamine neuromodulator dopamine (DA) plays a critical role in the brain, and the ability to directly measure dopaminergic activity is essential for understanding its physiological functions. We therefore developed the first red fluorescent GPCR-activation–based DA (GRAB<sub>DA</sub>) sensors and optimized versions of green fluorescent GRAB<sub>DA</sub> sensors following our previous studies. In response to extracellular DA, both the red and green GRAB<sub>DA</sub> sensors have a large increase in fluorescence (ΔF/F<sub>0</sub> values of 150% and 340%, respectively), with subcellular resolution, subsecond kinetics, and nanomolar to submicromolar affinity. Moreover, both the red and green GRAB<sub>DA</sub> sensors readily resolve evoked DA release in mouse brain slices, detect compartmental DA release in live flies with single-cell resolution, and report optogenetically elicited nigrostriatal DA release as well as mesoaccumbens dopaminergic activity during sexual behavior in freely behaving mice. Importantly, co-expressing red GRAB<sub>DA</sub> with either green GRAB<sub>DA</sub> or the calcium indicator GCaMP6s provides a robust tool for simultaneously tracking neuronal activity and dopaminergic signaling in distinct circuits <i>in vivo</i>.
Challenges to Healthy Eating for People With Diabetes in a Low-Income, Minority Neighborhood
Authors: Jessica Y. Breland, Lisa M. McAndrew, Rachel L. Gross, Howard Leventhal, Carol R. Horowitz
Journal: Diabetes Care (2013)

This study used qualitative interviews with black and Latino participants with diabetes to further understanding about types of foods eaten, food preparation, sources of foods and meals, communication with providers, and effects of race and ethnicity on eating in this population.Researchers recruited black and Latino adults from East Harlem, New York, to participate in four English and Spanish focus groups. Discussions were transcribed, coded, and analyzed to uncover prevalent themes, which were interpreted with the Common Sense Model of Self-Regulation.Thirty-seven adults with diabetes participated in four focus groups. The following four major themes emerged from the analyses: 1) The food environment limited participants' access to healthy foods; 2) understanding of diabetes and communication with clinicians about healthy eating was limited and abstract; 3) the short-term, negative consequences of healthy eating outweighed the benefits; and 4) stress, in large part from poverty and discrimination, was seen as a causal factor for both poor eating and diabetes.Participants' responses indicated that using healthy eating to control diabetes does not provide immediate, tangible results. Thus, these participants followed their own common sense to guide their diabetes management and improve their health. Clinicians may be better able to help patients eat healthfully if they consider these factors during medical visits.
Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737
Authors: Victoria Del Gaizo Moore, Jennifer R. Brown, Michael Certo, Tara M. Love, Carl D. Novina, Anthony Letai
Journal: Journal of Clinical Investigation (2007)

Antiapoptotic B cell leukemia/lymphoma 2 (BCL2) family proteins are expressed in many cancers, but the circumstances under which these proteins are necessary for tumor maintenance are poorly understood. We exploited a novel functional assay that uses BCL2 homology domain 3 (BH3) peptides to predict dependence on antiapoptotic proteins, a strategy we call BH3 profiling. BH3 profiling accurately predicts sensitivity to BCL2 antagonist ABT-737 in primary chronic lymphocytic leukemia (CLL) cells. BH3 profiling also accurately distinguishes myeloid cell leukemia sequence 1 (MCL1) from BCL2 dependence in myeloma cell lines. We show that the special sensitivity of CLL cells to BCL2 antagonism arises from the requirement that BCL2 tonically sequester proapoptotic BIM in CLL. ABT-737 displaced BIM from BCL2’s BH3-binding pocket, allowing BIM to activate BAX, induce mitochondrial permeabilization, and rapidly commit the CLL cell to death. Our experiments demonstrate that BCL2 expression alone does not dictate sensitivity to ABT-737. Instead, BCL2 complexed to BIM is the critical target for ABT-737 in CLL. An important implication is that in cancer, BCL2 may not effectively buffer chemotherapy death signals if it is already sequestering proapoptotic BH3-only proteins. Indeed, activator BH3-only occupation of BCL2 may prime cancer cells for death, offering a potential explanation for the marked chemosensitivity of certain cancers that express abundant BCL2, such as CLL and follicular lymphoma.
Determinants of Glomerular Volume in Different Cortical Zones of the Human Kidney
Authors: Terry Samuel, Wendy E. Hoy, Rebecca Douglas-Denton, Michael D. Hughson, John F. Bertram
Journal: Journal of the American Society of Nephrology (2005)

Enlarged glomerular size is a feature of focal segmental glomerulosclerosis, obesity-related glomerulopathy, diabetic nephropathy, and hypertension. The distribution of glomerular volumes within different cortical zones and glomerular volume alterations with age and obesity may contribute to understanding the evolution of these diseases. We analyzed the distributions of volumes of individual glomeruli in the superficial, middle, and juxtamedullary cortex of normal human kidneys using the disector/Cavalieri method. Volumes (V<sub>glom</sub>) of 720 nonsclerotic glomeruli (30 per kidney, 10 per zone) were estimated in autopsy kidneys of 24 American men, 12 aged 20 to 30 yr and 12 aged 51 to 69 yr. Black and white individuals were represented equally. The range of individual V<sub>glom</sub> within subjects varied from two- to eight-fold. There were no significant zonal differences in V<sub>glom</sub> in the young or those with body surface area (BSA) ≤ 2.11 m<sup>2</sup>. In contrast, superficial glomeruli in the older age group, in those with BSA &gt; 2.11 m<sup>2</sup>, and in white subjects were significantly larger than juxtamedullary glomeruli. Black subjects tended toward larger V<sub>glom</sub> than white subjects, and this difference was significant and most marked in the juxtamedullary zone and independent of age, BSA, and glomerular number. There is a wide range in individual V<sub>glom</sub> in adults. BSA, race, and age independently influence V<sub>glom</sub> in different zones of the renal cortex. These findings might reflect processes of aging and susceptibility factors to renal disease.
PYLORIC AND DUODENAL STENOSIS IN MONGOLIAN CHILDREN
Authors: C. P. Lapage
Journal: BMJ (1932)

of fish liver has also been used in the treatment of six cases of pernicious anaemia by Connery,8 and although the results were not so striking as those of our own series, a satisfactory response was produced in every case.It may be safely concluded, therefore, that fish liver contains the same active blood-regenerating substance as is present in mammalian liver.It need scarcely be added that the economic possibilities of this new remedy are of great importance, both to the patient suffering from pernicious anaemia and to the fish industry.At present the extract is being made from whiting, haddock, and cod livers, while a preparation of monk-fish liver is ready for trial.It will be possible to obtain fresh fish liver at a fraction of the cost of mam- malian liver, and since the expense entailed in the manufacture of the extract should be similar to that of mam- malian liver extract, the cost to the patient should be much reduced.A valuable by-product-fish oil-will help to reduce the cost still further.The fish industry will benefit by having an outlet for the sale of fish livers, much of which at present is scarcely marketable.