tbuckley/cabot-search huggingface dataset:
Natural History of Chronic Hepatitis B Virus Infection: What We Knew in 1981 and What We Know in 2005
Authors: Hyung Joon Yim, Anna Suk-Fong Lok
Journal: Hepatology (2006)

Remarkable progress has been made in our understanding of the natural history of chronic hepatitis B virus (HBV) infection in the past 25 years. Availability of sensitive HBV DNA assays and application of sophisticated immunological techniques led to the recognition that HBV replication persists throughout the course of chronic HBV infection, and host immune response plays a pivotal role in HBV-related liver disease. Knowledge of the HBV genome organization and replication cycle led to the unraveling of HBV genotypes and molecular variants, which contribute to the heterogeneity in outcome of chronic HBV infection. The natural course of chronic HBV infection is now perceived as consisting of 4 phases: immune tolerance, immune clearance [hepatitis B e antigen (HBeAg)-positive chronic hepatitis], inactive carrier state, and reactivation (HBeAg-negative chronic hepatitis B). Understanding the dynamic nature of chronic HBV infection is crucial in the management of HBV carriers and underscores the need for long-term monitoring. Accumulating evidence indicates that antiviral therapy can prevent progression of HBV-related liver disease, particularly among patients with sustained response. Newer antiviral therapies with improved efficacy and decreased risk of resistance may lead to a complete revision of the chapter on the natural history of chronic HBV infection on the occasion of the golden jubilee of HEPATOLOGY.
A LACRIMAL NEEDLE AND PUNCTUM DILATOR COMBINED
Authors: Arthur S. Tenner
Journal: JAMA (1924)

I have used this needle for the last two months with such satisfaction that it has seemed to me worthy of publication of its merits. It has a small, solid tip with a lateral fenestration 1.5 mm. back of the tip. It is conical, increasing in diameter from about 22 gage at the tip to about 17 gage at the base. It is without any curve, and is about 2 cm. long. The material is sterling silver and is not affected by silver salts or iodin. The hub has the regular standard Luer slip and can be used, therefore, with a Luer syringe of any size. It is advantageous, however, to use a well made syringe of domestic manufacture, such as a B-D Luer, for the reason that the imported syringes fit poorly, resulting either in leakage or in the needle's flying off during pressure. The advantage of the small
Internalization of 125I-Insulin by IM-9 Cultured Human Lymphocytes: A Comparison Between A14-Monoiodo-Pork and Biosynthetic Human Insulin
Authors: Jean Louis Carpentier, Philippe A Halban, Albert E Renold, Lelio Orci
Journal: Diabetes Care (1981)

Human insulin synthesized from A- and B-chains separately produced in Escherichia coli from cloned genes was characterized by examining its interaction biochemically and morphologically with IM-9 cultured human lymphocytes. Biosynthetic human insulin (BHI) behaves similarly to pork insulin with respect both to its binding properties and to the rate and magnitude at which it is internalized by the cells.
Most cases of research misconduct go undetected, conference told
Authors: Richard Smith
Journal: BMJ (2008)

Questionable research practices are common and probably do more damage to science than the “big three” of fabrication, falsification, and plagiarism, said Nick Steneck, consultant to the US Office of Research Integrity, last week at a conference on the governance of good research conduct in the United Kingdom.

The priority in the United States had been to eliminate serious research misconduct, said Professor Steneck, but now much more attention is being paid to preventing “questionable research practices,” which take many forms, including poor design, incomplete literature review, failure to report some evidence, unreported outcomes, failure to declare …
CXCR3 blockade protects against Listeria monocytogenes infection–induced fetal wastage
Authors: Vandana Chaturvedi, James M. Ertelt, Tony T. Jiang, Jeremy M. Kinder, Lijun Xin, Kathryn J. Owens, Helen N. Jones, Sing Sing Way
Journal: Journal of Clinical Investigation (2015)

Mammalian pregnancy requires protection against immunological rejection of the developing fetus bearing discordant paternal antigens. Immune evasion in this developmental context entails silenced expression of chemoattractant proteins (chemokines), thereby preventing harmful immune cells from penetrating the maternal-fetal interface. Here, we demonstrate that fetal wastage triggered by prenatal Listeria monocytogenes infection is driven by placental recruitment of CXCL9-producing inflammatory neutrophils and macrophages that promote infiltration of fetal-specific T cells into the decidua. Maternal CD8+ T cells with fetal specificity upregulated expression of the chemokine receptor CXCR3 and, together with neutrophils and macrophages, were essential for L. monocytogenes-induced fetal resorption. Conversely, decidual accumulation of maternal T cells with fetal specificity and fetal wastage were extinguished by CXCR3 blockade or in CXCR3-deficient mice. Remarkably, protection against fetal wastage and in utero L. monocytogenes invasion was maintained even when CXCR3 neutralization was initiated after infection, and this protective effect extended to fetal resorption triggered by partial ablation of immune-suppressive maternal Tregs, which expand during pregnancy to sustain fetal tolerance. Together, our results indicate that functionally overriding chemokine silencing at the maternal-fetal interface promotes the pathogenesis of prenatal infection and suggest that therapeutically reinforcing this pathway represents a universal approach for mitigating immune-mediated pregnancy complications.
Severe diaphragm weakness in multiple sclerosis.
Authors: C B Cooper, P S Trend, C M Wiles
Journal: Thorax (1985)

Respiratory failure is only rarely associated with multiple sclerosis.' 2 We describe a patient in whom a diagnosis of demyelinating disease was established and who presented in relapse with acute bilateral diaphragm weakness associated with other signs suggestive of a lesion extending up to the cervicomedullary junction.He developed respiratory failure and required mechanical ventilation. Case reportA 41 year old caucasian male presented in February 1981 with vertigo, diplopia, paraesthesiae, and urinary reten- tion.He was ataxic and had an internuclear ophthalmo- plegia and bilateral extensor responses.Lumbar cerebro- spinal fluid showed 41 lymphocytes/mm3 and a protein con- centration of 2 g/l.He was treated with dexamethasone and recovered.In March 1982 he presented with typical left optic neuritis responding poorly to corticosteroid treatment.Later that year he had sensory disturbance over the trunk and gait ataxia.In May 1983
STANDARDIZATION OF DIGITALIS
Authors: H. A. McGuigan
Journal: JAMA (1934)

To the Editor:—  The digitalis committee (The Journal, March 17, p. 862) endorses the cat method for the standardization of digitalis and gives some valuable information concerning it. It then states that tablets of digitalis leaves made up to the strength of 1 cat unit, ½ cat unit and 2 cat units have proved satisfactory in clinical use. Also liquid preparations of digitalis should be put up so that 1 cc. contains the equivalent of 1 cat unit.  I should like to ask: In clinical work why not leave the cat in the laboratory? What clinicians want is an assured active preparation. Most of them do not know what a cat unit means, and why should they be asked to remember it? It adds only to confusion to say that 1 cc. contains a cat unit. If the cat must be mentioned, it would be sufficient to state that the
Teaching medical students and doctors how to communicate risk
Authors: P. Sedgwick
Journal: BMJ (2003)

The need for doctors to have proficient communication skills is well recognised,1 but teaching students how to communicate risk to patients seems to have received little attention in the undergraduate medical curriculum. Primarily it is statisticians who teach the concept of probability. This ultimately translates into the communication of risk that informs the clinical consultation. Although students need to appreciate the basics of statistical methods and know the different ways to convey risk,2 it is particularly important that they have the opportunity to practise these skills under safe conditions and receive constructive feedback.1 3

The recently established graduate entry programme at St George's Hospital Medical School in London has an integrated curriculum across all years.4 The course is delivered by using problem based learning whereby students use “triggers” from a problem case or scenario to identify their own learning issues.5 It has …
Lhx6 Directly Regulates Arx and CXCR7 to Determine Cortical Interneuron Fate and Laminar Position
Authors: Daniel Vogt, Robert F. Hunt, Shyamali Mandal, Magnus Sandberg, Shanni N. Silberberg, Takashi Nagasawa, Zhengang Yang, Scott C. Baraban, John L.R. Rubenstein
Journal: Neuron (2014)
Phonosurgery: Theory and Practice
Authors: Byron J. Bailey
Journal: JAMA (1990)

"Phonosurgery" is the term used to include a variety of operations designed to improve the quality of the voice. Some of these procedures have been around for decades (eg, injection of Teflon paste into a paralyzed vocal cord), while others are new and controversial. This book focuses on the latter, with particular emphasis on laryngeal framework surgery. The author, Professor Isshiki, has been trained in otolaryngology and plastic surgery and is internationally renowned for his pioneering efforts to increase our understanding of the fundamental basis for poor voice quality after injury, scarring, or paralysis involving this delicate and complex neuromuscular structure. Even the adverse effects of aging on voice quality have been carefully analyzed, and surgical procedures have been designed to restore a stronger, more youthful sound to the voice. One might think of these procedures as "voice-lifts," or the acoustical counterpart to face-lifts. Dr Isshiki devotes the first portion
Effect of progesterone pretreatment on cadmium toxicity in male Fischer (F344/NCr) and Wistar (WF/NCr) rats.
Authors: N Shiraishi, R A Barter, H Uno, M P Waalkes
Journal: Environmental Health Perspectives (1994)

A previous report indicated that progesterone pretreatment can markedly reduce cadmium (Cd) toxicity in male NAW mice. Therefore we examined the effects of progesterone pretreatment on Cd toxicity in male Fischer (F344) and Wistar (WF) rats. A single subcutaneous injection of 10 or 30 mumole (CdCl2)/kg proved nonlethal over 24 hr but caused the typical spectrum of testicular lesions in these rats. Moreover, when F344 rats were pretreated with progesterone (100 mg/kg, sc, at -48, -24, and 0 hr) and then given cadmium (20 mumole CdCl2/kg, 0 hr), this dose of cadmium proved very toxic, unexpectedly causing 53% mortality. Progesterone pretreatment had no effect on cadmium-induced lethality in WF rats or on testicular lesions in either strain. Significant elevations in serum lactate dehydrogenase (LDH) activity, indicative of hepatotoxicity, were also observed in progesterone-pretreated F344 rats given cadmium as compared to rats given Cd alone. Progesterone did not induce increases in hepatic or renal metallothionein (MT) and hepatic or testicular MT-I mRNA levels in F344 rats. In contrast, levels of the testicular cadmium-binding protein (TCBP) in progesterone-pretreated F344 rats were doubled. This increase in TCBP provided no protection against cadmium toxicity in the testes. These results indicate that, in contrast to previously reported data for mice, progesterone pretreatment increased the lethality of cadmium in male F344 rats and had no effect on cadmium-induced testicular toxicity in F344 and WF rats.
Surgical Significance of the Thymus
Authors: David P. Boyd, Franklyn P. Gerard
Journal: New England Journal of Medicine (1960)

THE thymus has been called the organ of mystery. Galen so described it and considered it a pad to protect the vena cava from the hard inner surface of the sternum. Today, one suspects that this body is more important than Galen believed, but little is known of its function. Certainly, it is of importance in myasthenia gravis, and it frequently enters into the diagnosis of mediastinal tumors. These two considerations have prompted us to review our experience as the basis for this report.Twenty-four thymectomies were performed from 1928–1958. Seven of these were in patients with myasthenia gravis who . . .
Hyperactivity in the Lower Sternal Region With Tc-99m Sestamibi: Possible Cardiac Origin
Authors: FABIENNE SERVAIS, ALAIN SERET, DIDIER BLOCKLET, ANDRÉ LENAERS, ANDRÉ SCHOUTENS
Journal: Clinical Nuclear Medicine (1998)

Scintimammography performed with Tc-99m sestamibi in a 63-year-old woman with a history of mitral valve replacement and pulmonary hypertension demonstrated that the frequently observed sternal hyperactivity on anterior planar views could arise from the myocardium. Caution therefore should be taken before diagnosing hyperactivity in the lower sternal region as neoplastic involvement.
CLASSIFICATION OF MYELOMA PROTEINS, BENCE JONES PROTEINS, AND MACROGLOBULINS INTO TWO GROUPS ON THE BASIS OF COMMON ANTIGENIC CHARACTERS
Authors: Mart Mannik, Henry G. Kunkel
Journal: The Journal of Experimental Medicine (1962)

Antisera to normal 7S gamma-globulin and to Bence Jones proteins permit the grouping of myeloma proteins (gamma and beta 2A types), Bence Jones proteins, and the Waldenström type macroglobulins into two fundamental antigenic groups. The antigenic determinants responsible for this grouping are common to all these proteins which fall in the general category of immunoglobulins. Antisera to Bence Jones proteins were particularly useful for this classification since they failed to react with the proteins of the opposite group. These antisera also permit the grouping of normal 7S gamma-globulin into two major types. The Bence Jones proteins from individual patients were found to correspond in antigenic group to that of the serum myeloma protein. Studies with antisera to 7S gamma-globulin and to Bence Jones proteins indicated that the Bence Jones proteins were antigenically identical to a portion of the corresponding multiple myeloma protein molecules.
A Comparison of Surgical Rates in Canada and in England and Wales
Authors: Eugene Vayda
Journal: New England Journal of Medicine (1973)

Abstract Comparison showed that surgical rates in Canada (1968) were 1.8 times greater for men and 1.6 times greater for women than in England and Wales (1967). The age-standardized and sex-specific rates for diverse elective and discretionary operations — such as tonsillectomy and adenoidectomy, hemorrhoidectomy and inguinal herniorrhaphy —were two or more times higher in Canada than in England and Wales. In elderly people, mortality from diseases of the gallbladder was twice as high in Canada as in England and Wales, but the Canadian cholecystectomy rate was more than five times greater. Because the compared rates for individual surgical procedures are suitably standardized, some of the disparities between the two countries are probably due to sources other than the incidence and prevalence of disease. Among the contributing factors are divergent styles of treatment and indications for surgery, but the main determinants may be the differences in organization and payment of health services, in functional "limited licensure" and in the numbers of surgeons and hospital beds. (N Engl J Med 289:1224–1229, 1973)
Biology of Neuroglia
Authors: Mary Jane C. Showers
Journal: JAMA (1966)

Neurohistochemistry, edited by C. W. M. Adams, 753 pp, 300 illus, $29, Amsterdam and New York: Elsevier Publishing Co., 1965.  Biology of Neurogliais a compilation of the invited papers presented in 1963 in Buenos Aires at the International Symposium of Neurologic Research. It attempts to coordinate interdisciplinary data relevant to neuroglia that have accrued from the application of biochemical, cytochemical, electronmicroscopic and physiologic, including microphysiologic, techniques.  The dynamic involvement of astrocytes and ependymal cells is demonstrated in the ionic and osmotic involvement of the central nervous system particularly with sodium. Glycogen metabolism of the astroglia was found to be altered in circumstances affecting an astroglial-neuronal metabolic unit. The unresolved problem of cerebral edema was approached from several avenues by way of the neuroglia which appear to be related in multiple ways with the edematous process. The edema was a variable dependent upon pathogenesis. Synaptic events, myelination and allergic responses,
Abstract 2203: Pathway analysis of genome-wide association study data highlights taste transduction and metabolic pathways and esophageal squamous cell carcinoma susceptibility
Authors: Paula L. Hyland, Han Zhang, Qi Yang, Shih-Wen Lin, Dennis Maeder, Nan Hu, Ze-Zhong Tang, Hua Su, Lemin Wang, Chaoyu Wang, Ti Ding, Jin-Hu Fan, You-Lin Qiao, William Wheeler, Carol Giffen, Laurie Burdett, Zhaoming Wang, Stephen J. Chanock, Sanford M. Dawsey, Neal D. Freedman, Christian C. Abnet, Alisa M. Goldstein, Kai Yu, Philip R. Taylor
Journal: Cancer Research (2014)

Abstract Background: In China, esophageal cancer is the fourth leading cause of cancer death and essentially all cases are histologically esophageal squamous cell carcinoma (ESCC). Agnostic pathway-based analyses applied to GWAS data can identify biological pathways and/or groups of genes enriched with disease-associated variants whose individual effect sizes may be too small to be detected by standard single locus methods. Methods: We used the adaptive rank-truncated product (ARTP) method to analyze 1,827 pathways containing 69,420 genes in GWAS data from 1942 ESCC cases and 2111 controls with Chinese ancestry. Pathways were retrieved from five databases: KEGG, BioCarta, Reactome, HumanCys and NCI-Nature curated. Statistical significance was determined by permutation. Results: Associations with ESCC risk (P&amp;lt;0.001) were observed for 60 pathways, which included overlapping pathways from different sources predominantly associated with cell cycle control and signaling, DNA repair, and apoptosis. After excluding genes with previous GWAS hits from the pathway analysis, the KEGG taste transduction pathway and the KEGG metabolic pathways were significantly associated with risk of ESCC (P&amp;lt;0.001). The most significant genes (P&amp;lt;0.001) in these pathways were TAS2R13, TAS2R42, TAS2R14, TAS2R46 and TAS2R50, and MTAP, GAPDH, DCTD, POLD2 and AMDHD1, respectively. Significance: This approach provides new insights into the collective role of genetic variants and ESCC risk in Han Chinese and suggests that genetic alterations associated with taste transduction and metabolic pathways may contribute to cancer susceptibility. Citation Format: Paula L. Hyland, Han Zhang, Qi Yang, Shih-Wen Lin, Dennis Maeder, Nan Hu, Ze-Zhong Tang, Hua Su, Lemin Wang, Chaoyu Wang, Ti Ding, Jin-Hu Fan, You-Lin Qiao, William Wheeler, Carol Giffen, Laurie Burdett, Zhaoming Wang, Stephen J. Chanock, Sanford M. Dawsey, Neal D. Freedman, Christian C. Abnet, Alisa M. Goldstein, Kai Yu, Philip R. Taylor. Pathway analysis of genome-wide association study data highlights taste transduction and metabolic pathways and esophageal squamous cell carcinoma susceptibility. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2203. doi:10.1158/1538-7445.AM2014-2203
ASSOCIATION OF INTERVENTIONAL CARDIOLOGY BOARD CERTIFICATION AND IN-HOSPITAL OUTCOMES OF PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTIONS
Authors: Paul Nicolas Fiorilli, Karl Minges, Jeph Herrin, John Messenger, Henry Ting, Brahmajee Nallamothu, Rebecca Lipner, Eric Holmboe, joseph Brennan, Jeptha Curtis
Journal: Journal of the American College of Cardiology (2014)
The Enforcement of Medical Laws.
Authors: George E. Davis
Journal: JAMA (1901)

Lawrenceburg, Ky., Nov. 23, 1901. <h3>To the Editor:</h3> —The editorial and original articles in the issue ofThe Journalof November 16, discussing the enforcement of medical laws, are worthy the attention and approbation of every member of the profession in America. As a Kentuckian, I appreciate the tribute you pay to the profession of Kentucky in its effective work in ridding the state of quacks. Individually, however, on account of my recent experience in dealing with a quack, I am not so enthusiastic and feel that my efforts in protecting the profession and the public will hardly be so "strenuous" in the future as they have been in the past. Your suggestion that "what is needed to enforce the medical laws is a well-organized state society with its branches ramifying into every county and with a paid attorney of its own, to act for the profession, independent of, or
A1.70 Sterile inflammation occurs in a TLR9-independent manner in experimental arthritis and rheumatoid arthritis
Authors: Julie Mussard, Matthieu Ribon, Gaëlle Clavel, Marie-Christophe Boissier, Patrice Decker
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Rheumatoid arthritis (RA) is an inflammatory disease of unknown etiology. Toll-like receptor (TLR) 9 recognizes pathogen-derived DNA and even self DNA under certain circumstances. Interestingly, environmental factors and especially bacterial infections have been suggested to favour RA development. In addition, TLR9 might also recognize damage-associated molecular patterns (DAMP) in RA. However, the involvement of TLR9 in RA remains unclear. Therefore, we have investigated whether TLR9 is necessary for disease development in a mouse model of RA and we analysed TLR9 expression in human samples. <h3>Materials and Methods</h3> Disease development was followed in the collagen-induced arthritis (CIA) mouse model. The impact of TLR9 was evaluated by comparing wild-type (WT) mice and TLR9-knockout (KO) true littermates. Arthritis was followed by clinical score evaluation. Inflammation and bone destruction were estimated by histology. Anti-collagen antibody and blood cytokine levels were measured by ELISA. B and T lymphocytes as well as neutrophils were analysed by flow cytometry. Osteoclastogenesis was analysed by culturing bone marrow cells with M-CSF and RANKL and then counting TRAP-positive multinucleated cells by microscopy. Moreover, TLR9 expression was analysed ex vivo by flow cytometry on whole blood from healthy donors and RA patients. <h3>Results</h3> TLR9 is not required for arthritis development in CIA as TLR9-KO mice strongly developed clinical arthritis. Accordingly, WT and KO mice produced similar levels of anti-collagen antibodies. As a control, we verified that WT and KO mice responded to complete Freund’s adjuvant. Moreover, inflammation and joint destruction were observed in both WT and TLR9-KO mice. In agreement with those observations, no statistically significant difference was noted between WT and KO mice regarding the percentage or the activation of lymphocytes and neutrophils in the blood, spleen and lymph nodes. The impact of TLR9 on cytokine secretion and osteoclastogenesis in vivo is presently being analysed. In human samples, we have shown that leukocytes from healthy donors and RA patients express TLR9 at the same extent. <h3>Conclusions</h3> TLR9-KO mice clearly develop arthritis. Immune cells from RA patients do not over-express TLR9 in comparison to healthy donors. Our results thus suggest that TLR9 does not play a crucial role in inflammatory arthritis development in the CIA model and that in vivo TLR9 ligands do not up-regulate TLR9 in RA patients. This also suggests that TLR9 is not strongly involved in the recognition of DAMP in RA.