tbuckley/cabot-search huggingface dataset:
Awaiting a New Era of Cancer Immunotherapy
Authors: Cheng William Hong, Qi Zeng
Journal: Cancer Research (2012)

A major challenge in cancer therapy is the lack of specificity for cancer cells. Antibody-based therapies have better specificity and, thus, improved efficacy over standard chemotherapy regimens. Monoclonal antibodies (mAb) constitute the most rapidly growing class of human therapeutics and are proven agents for recognizing and destroying malignant cells. However, the development of antibody therapies has focused only on targeting extracellular (cell-surface or secreted) proteins rather than intracellular targets (within cells, such as phosphatases and/or kinases and transcription factors), because antibodies are generally believed to be too large to enter cells, resulting in a large untapped source of intracellular therapeutic targets. Recently, we presented evidence that suggests that intracellular proteins with high expression in cancer cells are useful targets for mAb-based or vaccination immunotherapies, thus challenging current understanding. Here, we further discuss the concept and future uses of these immunotherapies against a large pool of intracellular oncoproteins for cancer therapy. This line of research has the potential to vastly expand the field of antibody therapy and usher in a new era of cancer vaccines.
Handicap in Darier's disease and Hailey-Hailey disease
Authors: A. HARRIS, S.M. BURGE, P.J. DYKES, A.Y. FINLAY
Journal: British Journal of Dermatology (1996)

One hundred and thirty-seven patients with Darier's disease and 66 patients with Hailey-Hailey disease completed the Dermatology Life Quality Index (DLQI). The average DLQI score for Darier's disease was 5.89 (19.6% of the maximum score), median = 4, quartiles: 1.9. The average DLQI score for Hailey-Hailey disease was 6.06 (20.2% of the maximum score), median = 5, quartiles: 2.9. The DLQI score did not correlate with the physician's assessment of clinical severity in both diseases, thus emphasizing the importance of remembering the potential for handicap even in patients with disease that seems to be mild. The domains of the questionnaire with the highest mean scores in both diseases were for questions relating to symptoms and feelings. Domains relating to personal relationships and work obtained low mean scores even in severe disease. It is encouraging that most patients with Darier's disease and Hailey-Hailey disease maintain good relationships at work and home and seem to be able to adapt to their skin disease.
Arterial imaging with a new forward-viewing intravascular ultrasound catheter, II. Three-dimensional reconstruction and display of data.
Authors: K H Ng, J L Evans, M J Vonesh, S N Meyers, T A Mills, B J Kane, W N Aldrich, Y T Jang, P G Yock, M D Rold
Journal: Circulation (1994)

BACKGROUND: Current intravascular ultrasound (IVUS) catheters provide transverse imaging at the level of the ultrasound transducer. This limits imaging to large-diameter segments without critical atherosclerotic narrowings. We have developed a prototype 20-MHz forward-viewing IVUS catheter that provides two-dimensional sector imaging distal to the catheter tip. A present limitation of this technique is that the catheter must be manually rotated to obtain multiple longitudinal views required to integrate the segment into a three-dimensional matrix. To overcome this, we have developed an algorithm that reconstructs these multiple two-dimensional forward-viewing IVUS images into a three-dimensional matrix for more complete depiction of the segment distal to the ultrasound catheter. This algorithm allows display and multidimensional slicing of the three-dimensional reconstruction. METHODS AND RESULTS. To test our algorithms, five arterial segments (three canine aortas, two human femoral arteries) were evaluated in vitro. In each segment, 36 forward-viewing longitudinal slices were collected, digitized, processed, and reoriented to produce a three-dimensional reconstruction (3DR) matrix. The matrix data were sliced into parallel transverse sections and compared with morphometric interpretation of histological sections (Histo). As a result, image data could be reconstructed for a distance of 2.0 cm ahead of the catheter. 3DR easily demonstrated wall and luminal morphology and provided transverse IVUS images comparable to the histological specimens. A good correlation was noted between Histo- and 3DR-determined luminal diameters (LD) and luminal areas: 3DR LD = 1.4 Histo LD-0.4, r = .86; 3DR LD = 0.7 +/- 0.20 cm (mean +/- SD); and Histo LD = 0.7 +/- 0.13 cm. CONCLUSIONS: These preliminary data demonstrate the feasibility of 3DR of forward-viewing IVUS data. This method allows rapid, detailed analysis of diseased arterial segments previously unavailable with standard IVUS and may permit better targeting of interventional techniques.
Drugs Employed for the Suppression of Immunologic Responsiveness
Authors: Alan C. Aisenberg
Journal: New England Journal of Medicine (1965)

SCINCE the grafting of organs between genetically nonidentical individuals uniformly leads to immunologic reaction against the graft and its subsequent death and rejection, successful homotransplantation requires immunologic modification of the recipient. At the time of writing such suppression of immunologic reactivity has been most readily obtained with drugs. It should be remarked at the outset that immunologic suppression either with drugs or by any other means is not a simple or well understood event. The complexity arises from the phenomenon of tolerance1 originally observed in neonatal animals by Medawar, but now recognized as occurring under a variety of circumstances in . . .
PENTOTHAL SODIUM ANAESTHESIA
Authors: O. J. Murphy
Journal: BMJ (1936)

fundus and may be abolished by infiltrating the area of skin involved.This pain is probably an example of peritoneo-cutaneous radiation.The local anaesthesia is effective for three to eight hours, and the fact that it has been found possible to ensure absolutely painless childbirth proves the truth of Macken- zie's theory of referred pain so far as the uterus is con- cerned, and at the same time offers the hope that an improved technique will ensure painless childbirth without any risk to the mother or the child, and without the continuous attendance of an anaesthetist.
The Study of the Brain. A Companion Text to the Stereoscopic Atlas of Neuroanatomy
Authors: C. G. SMITH
Journal: American Journal of Psychiatry (1955)

country, relatively little biochemical research is being directed toward it."Infantile depressions are described by Spitz, and children's reaction to the death of a parent by Keeler.The psychoanalytic interpretation of depressive pat.terns is presented by Rado, under the title of "Hedonic Con- trol, Action-Self and the Depressive Spell."The physical therapies, as applied to depressions, are discussed by Alex- ander, Davidoff and Russ and Kalinowsky.It is quite obvious that we are very far from a complete understanding of the etiology of depressive states, although a continuing investigation along psychologic, psychodynamic, physiologic, biochemical and cultural lines, such as this book presents, sheds further light on this very interesting field of psychiatry.
Schooling for the Learning Disabled: A Selective Guide to LD Programs in Elementary and Secondary Schools Throughout the United States
Authors: Charles D. Aring
Journal: JAMA (1985)

The family with a child who has a learning disability is subject to confusion and heartache, particularly if there has been no help forthcoming from the experts. The routine school situation is not set up to encompass mavericks, and the confusion is compounded by lack of recognition of the true nature of the condition. Not a few of the afflicted are regarded as showing aberrant behavior, which they are prone to exhibit when exposed to unsympathetic or uninformed authority. This is a guide to the alternatives in education available to the child with a learning disability. Besides an outline of the state of the art, it contains descriptions of 50 diverse programs devoted to children with learning disability in elementary and secondary schools in the Northeastern, Southeastern, Midwestern, and Far Western United States. The authors proposed to enlarge and update the list in 1984 through 1985 and solicit suggestions to
Treatment of Rheumatoid Arthritis by Selective Inhibition of T-Cell Activation with Fusion Protein CTLA4Ig
Authors: Joel M. Kremer, Rene Westhovens, Marc Leon, Eduardo Di Giorgio, Rieke Alten, Serge Steinfeld, Anthony Russell, Maxime Dougados, Paul Emery, Isaac F. Nuamah, G. Rhys Williams, Jean-Claude Becker, David T. Hagerty, Larry W. Moreland
Journal: New England Journal of Medicine (2003)

Effective new therapies are needed for rheumatoid arthritis. Current therapies target the products of activated macrophages; however, T cells also have an important role in rheumatoid arthritis. A fusion protein — cytotoxic T-lymphocyte–associated antigen 4–IgG1 (CTLA4Ig) — is the first in a new class of drugs known as costimulation blockers being evaluated for the treatment of rheumatoid arthritis. CTLA4Ig binds to CD80 and CD86 on antigen-presenting cells, blocking the engagement of CD28 on T cells and preventing T-cell activation. A preliminary study showed that CTLA4Ig may be effective for the treatment of rheumatoid arthritis.
Functional Behavior of the Microcirculation
Authors: F. T. Jung
Journal: JAMA (1961)

The aim of this book is to describe microcirculatory activity—the behavior of venules, arterioles, and especially capillaries—with emphasis on the close interdependence between structure and function, so as to enable the reader to deal more adequately with the accumulating mass of clinical and pathological information on the subject. An opening chapter outlines some general concepts. It is followed by chapters on the structure of the microcirculation, special and regional considerations, endothelium, functional behavior and local regulation, normal and abnormal vascular reactivity, capillary permeability, mechanisms of transcapillary exchange, vascular response to tissue injury, chemical mediators of tissue injury, experimental shock, and circulatory homeostasis. Neither the text nor the 11 illustrations have the vividness of motion pictures now available. The reader is likely to be confused when the author writes "antedated" for "antiquated," "monitor" for "regulate," and "stigmata" for "stomata." The only mathematical expression in the book (page 84) is misprinted, so
The emergence of top-down proteomics in clinical research
Authors: John P Savaryn, Adam D Catherman, Paul M Thomas, Michael M Abecassis, Neil L Kelleher
Journal: Genome Medicine (2013)

Proteomic technology has advanced steadily since the development of 'soft-ionization' techniques for mass-spectrometry-based molecular identification more than two decades ago. Now, the large-scale analysis of proteins (proteomics) is a mainstay of biological research and clinical translation, with researchers seeking molecular diagnostics, as well as protein-based markers for personalized medicine. Proteomic strategies using the protease trypsin (known as bottom-up proteomics) were the first to be developed and optimized and form the dominant approach at present. However, researchers are now beginning to understand the limitations of bottom-up techniques, namely the inability to characterize and quantify intact protein molecules from a complex mixture of digested peptides. To overcome these limitations, several laboratories are taking a whole-protein-based approach, in which intact protein molecules are the analytical targets for characterization and quantification. We discuss these top-down techniques and how they have been applied to clinical research and are likely to be applied in the near future. Given the recent improvements in mass-spectrometry-based proteomics and stronger cooperation between researchers, clinicians and statisticians, both peptide-based (bottom-up) strategies and whole-protein-based (top-down) strategies are set to complement each other and help researchers and clinicians better understand and detect complex disease phenotypes.
HAIRY TONGUE IN PATIENTS RECEIVING PHENOTHIAZINES: PRELIMINARY REPORT
Authors: A. E. PAGANINI, M. ZLOTLOW
Journal: American Journal of Psychiatry (1959)

1. In an Indiscriminate survey of 896 patients at Pilgrim State Hospital, 20 patients possessed a hairy tongue. 2. Three of these patients were on no drugs whatsoever. 3. Seventeen patients were on chlorpromazine or chlorpromazine and mepazine. 4. Five of these 17 patients lost their hairy tongue afteŕ discontinuance of medication. It obviously cannot be stated definitely that the phenothiazines cause hairy tongue. But, as noted above, the 5 patients whose medication was discontinued lost their hairy tongue within 2 weeks. The rest of the patients still retain their hairy tongue while receiving their medication. This seems to point the finger of suspicion toward the phenothiazines, especially in view of the well-established concept that other drugs, notably the antibiotics, have been found to cause this condition. The occurrence of the 3 cases of hairy tongue in patients receiving no medication also points out the possibility of this being purely co-incidental. In addition, there lurks in the background of all these patients the fact that most of those with hairy tongue possess poor oral hygiene and are heavy smokers or tobacco chewers. Further studies of this problem are being carried out in an attempt to correlate all these findings. The observation is considered to be of interest and importance and is, therefore, reported in this preliminary study as a possible complication in the use of phenothiazine drugs.
IgE in the human placenta: why there?
Authors: E. Rindsjö, M. Joerink, N. Papadogiannakis, A. Scheynius
Journal: Allergy (2010)

Immunoglobulin E (IgE) antibodies are key effector molecules in the allergic inflammatory response and are also involved in the protection against extracellular parasites. Allergic symptoms often develop early in life, and the intrauterine environment has been proposed to play an important role in affecting the risk of later allergy development. The placenta constitutes a selective barrier between the maternal and foetal circulation. Recently, we reported that maternal IgE antibodies are present on foetal macrophages in the villous tissue of the human placenta irrespective of maternal allergy status. This review discusses the presence of IgE antibodies in the human placenta and its possible roles in normal and pathologic pregnancy. It also deals with the relationship between placental IgE and development of allergy during childhood. A better understanding of the role of IgE in placenta could give us clues on how to prevent allergy development in the future generations.
Systematic Review: Comparative Effectiveness of Medications to Reduce Risk for Primary Breast Cancer
Authors: Heidi D. Nelson
Journal: Annals of Internal Medicine (2009)

Background: Trials demonstrate the efficacy of medications to reduce the risk for invasive breast cancer. Purpose: To summarize benefits and harms of tamoxifen citrate, raloxifene, and tibolone to reduce the risk for primary breast cancer. Data Sources: MEDLINE and Cochrane databases from inception to January 2009, Web of Science, trial registries, and manufacturer information. Study Selection: Predefined eligibility criteria were used to select articles. English-language reports of randomized, controlled trials (RCTs) for benefits and RCTs and observational studies for harms were included. Data Extraction: Two reviewers assessed study data, quality, and applicability. Data Synthesis: Seven placebo-controlled RCTs and 1 head-to-head trial provide results for main outcomes. Tamoxifen (risk ratio, 0.70 [95% CI, 0.59 to 0.82]; 4 trials), raloxifene (risk ratio, 0.44 [CI, 0.27 to 0.71]; 2 trials), and tibolone (risk ratio, 0.32 [CI, 0.13 to 0.80]; 1 trial) reduce risk for invasive breast cancer compared with placebo by 7 to 10 per 1000 women per year. Tamoxifen and raloxifene reduce estrogen receptor–positive breast cancer but not estrogen receptor–negative breast cancer, noninvasive breast cancer, or mortality. All medications reduce fractures. Tamoxifen (risk ratio, 1.93 [CI, 1.41 to 2.64]; 4 trials) and raloxifene (risk ratio, 1.60 [CI, 1.15 to 2.23]; 2 trials) increase thromboembolic events by 4 to 7 per 1000 women per year; raloxifene causes fewer events than tamoxifen. Tamoxifen increases risk for endometrial cancer (risk ratio, 2.13 [CI, 1.36 to 3.32]; 3 trials) compared with placebo by 4 per 1000 women per year and causes cataracts compared with raloxifene. Tibolone causes strokes in older women. Limitations: Bias, trial heterogeneity, and a dearth of head-to-head trials limit this review. Data are lacking on doses, duration, and timing of the medications; long-term effects; and nonwhite and premenopausal women. Conclusion: Three medications reduce risk for primary breast cancer but increase risk for thromboembolic events (tamoxifen, raloxifene), endometrial cancer (tamoxifen), or stroke (tibolone). Primary Funding Source: Agency for Healthcare Research and Quality.
The unborn. Human values and responsibilities
Authors: H. O. Tiefel
Journal: JAMA (1978)

RECENT controversies about abortion, fetal experimentation, and the nontreatment of seriously diseased newborns raise a recurrent set of underlying questions: Are the unborn human beings? What is a human being and what is its value? What are our responsibilities toward beings whose human status is in doubt? This essay analyzes the interconnections between these questions and states as well as defends one of two alternative responses to them. One is never quite sure of the right sequence of these questions. The more traditional order, and the one followed here, is to begin with human status and to move to responsibilities or rights. But it is probably true that our definitions of "human being"—or even our choice of alternative basic terms such as "person" or "unborn child"—are deliberate and will allow us to support whatever moral responsibilities we wish to advocate. Yet, whether we start with asking who is a human
Mild Cystic Fibrosis Linked to Chromosome 7q22 Markers with an Uncommon Haplotype
Authors: A. Mcconkie-Rosell, Yuan-Tsong Chen, D. Harris, M. C. Speer, M. A. Pericak-Vance, Jia-Huan Ding, W. E. Highsmith, M. Knowles, S. G. Kahler
Journal: Annals of Internal Medicine (1989)

Cystic fibrosis is the commonest autosomal recessive genetic disorder among northern Europeans and their descendants. Recently, investigators have mapped the gene for cystic fibrosis to chromosome 7. We report the results of DNA linkage analysis in a consanguineous family with mild cystic fibrosis. The probes used in this study were pmet D, pmet H, XV-2c, KM. 19, and pJ3.11. Linkage to the identified cystic fibrosis locus of 7q22 was established with a peak logarithm of the odds (lod) score of 3.00 at a recombination fraction Θ = 0.00 using the tightly linked marker KM. 19. In addition, we found the D haplotype, which is not commonly associated with cystic fibrosis, to be segregating in this family. The D haplotype is composed of the 1.4-kb allele detectable by XV-2c and the 6.6-kb allele detectable by KM. 19. The three patients with cystic fibrosis who had consanguineous parents were homozygous DD, were among the least severely affected, and had no pancreatic insufficiency. The five patients with unrelated parents were heterozygous for the D haplotype and the commoner B haplotype, except one patient who was homozygous DD. All affected persons with pancreatic insufficiency had the DB genotype. These DNA linkage studies provide additional evidence for the existence of a cystic fibrosis allele that is associated with mild disease.
Computer-assisted image analysis of liver collagen: Relationship to Ishak scoring and hepatic venous pressure gradient
Authors: Vincenza Calvaruso, Andrew Kenneth Burroughs, Richard Standish, Pinelopi Manousou, Federica Grillo, Gioacchino Leandro, Sergio Maimone, Maria Pleguezuelo, Ilias Xirouchakis, Gian Piero Guerrini, David Patch, Dominic Yu, James O'Beirne, Amar Paul Dhillon
Journal: Hepatology (2008)

Abstract Histopathological scoring of disease stage uses descriptive categories without measuring the amount of fibrosis. Collagen, the major component of fibrous tissue, can be quantified by computer-assisted digital image analysis (DIA) using histological sections. We determined relationships between DIA, Ishak stage, and hepatic venous pressure gradient (HVPG) reflecting severity of fibrosis. One hundred fifteen patients with hepatitis C virus (HCV) who had undergone transplantation had 250 consecutive transjugular liver biopsies combined with HVPG (median length, 22 mm; median total portal tracts, 12), evaluated using the Ishak system and stained with Sirus red for DIA. Liver collagen was expressed as collagen proportionate area (CPA). Median CPA was 6% (0.2-45), correlating with Ishak stage (stage 6 range, 13%-45%), and with HVPG ( r = 0.62; P &lt; 0.001). Median CPA was 4.1% when HVPG was less than 6 mm Hg and 13.8% when HVPG was 6 mm Hg or more ( P &lt; 0.0001) and 6% when HVPG was less than 10 mm Hg and 17.3% when HVPG was 10 mm Hg or higher ( P &lt; 0.0001). Only CPA, not Ishak stage/grade, was independently associated by logistic regression, with HVPG of 6 mm Hg or more [odds ratio, 1.206; 95% confidence interval (CI), 1.094-1.331; P &lt; 0.001], or HVPG of 10 mm Hg or more (odds ratio, 1.105; 95% CI, 1.026-1.191; P = 0.009). CPA increased by 50% (3.6%) compared with 20% in HVPG (1 mm Hg) in 38 patients with repeated biopsies. Conclusion: CPA assessed by DIA correlated with Ishak stage scores and HVPG measured contemporaneously. CPA was a better histological correlate with HVPG than Ishak stage, had a greater numerical change when HVPG was low, and resulted in further quantitation of fibrosis in cirrhosis. (Hepatology 2009.)
CDC Recommendations for Opt-Out HIV Testing—Reply
Authors: John G. Bartlett, Kenneth Hugh Mayer
Journal: JAMA (2009)

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