tbuckley/cabot-search huggingface dataset:
Toll-free autoimmunity
Authors: Kendall Powell
Journal: The Journal of Experimental Medicine (2005)

Antiinflammatory eggsProteins secreted by parasite eggs might hold the key to the next antiinflammatory therapy.On page 1319, Smith and colleagues describe the first chemokine binding protein (CKBP) produced by a human pathogen and show that it can suppress acute inflammation in disease models.The blood-dwelling worm Schistosoma mansoni takes advantage of the host's immune system in two ways.It subverts specific inflammatory cells to help move its eggs from the intestinal vasculature to the feces, where they can be shed.It also suppresses the immune response in order to establish chronic infections, in part as shown here by keeping other inflammatory cells away from the eggs.This selective cell recruitment was not due solely to cytokine modulation, a known schistosome ability.As viruses produce chemokine binding proteins to neutralize host chemokines, the authors investigated whether S. mansoni might also make a chemokine binding protein to mask the eggs from strong inflammation.Smith and colleagues now identify a novel CKBP (smCKBP) that is secreted from schistosome eggs.This protein bound to the chemokines CXCL8 and CCL3 and prevented them from binding to their receptors on immune cells.Injecting mice with recombinant smCKBP blocked chemokinemediated neutrophil infiltration in response to a variety of inflammatory stimuli.This treatment, however, had no effect on chronic inflammation disorders such as arthritis.The authors suggest that, in nature, the parasite eggs secrete smCKBP to keep neutrophils and macrophages out of the surrounding granuloma so as not to attract immune attention, but pinning this mechanism down will require further study.Already tolerated by infected humans, smCKBP holds great potential as a new therapy for acute inflammatory diseases, especially those caused by neutrophilia.
Neuroblastoma: Clinical and Biological Manifestations
Authors: Audrey E. Evans
Journal: JAMA (1983)

This is a comprehensive volume on neuroblastoma that tries to include both clinical and biologic manifestations of this unusual tumor of childhood. The multiple authors deal authoritatively with their individual assignments, although there is some unevenness in the depth of the writing and the inclusion of details. The chapters dealing with therapy are more superficial, but this, in part, may be caused by the relative lack of success in the overall treatment of this tumor. By and large, those concerned with the biology of the tumor are more extensive in their treatment of the topic. The 14 chapters do not seem to follow an obvious order and are subdivided by age, site of the primary, diagnostic studies, basic biologic studies, and therapy, but readers can pick their way among the chapters with the aid of a detailed index. The information is current and up to date, and some of the
Studies on testosterone metabolism in subjects with testicular feminization syndrome
Authors: P. Mauvais-Jarvis, J. P. Bercovici, O. Crepy, F. Gauthier
Journal: Journal of Clinical Investigation (1970)

The metabolism of radioactive testosterone simultaneously administered intravenously and either orally or percutaneously has been studied in seven patients with the syndrome of testicular feminization and compared with that of normal males and females. This investigation was carried out in order to determine the relative contribution to urinary 17-oxo and 17β-hydroxy androstane steroids of labeled testosterone, according to its mode of administration. In normal males the yields of urinary 5α-androstane-3α,17β-diol (androstanediol) originating from either an intravenous or a percutaneous dose of testosterone were respectively 3 and 6 times higher than those arising from an oral dose which perfuses the liver directly. These data indicate that in normal males, testosterone might be 5α-hydrogenated outside the liver. By contrast in patient with feminizing testes, because the contribution to androstanediol of radioactive testosterone is identical whatever its mode of administration, the extrahepatic 5α-reduction of this substrate seems very unlikely.
Molecular Diagnostics of Hepatitis C Virus Infection
Authors: John D. Scott, David R. Gretch
Journal: JAMA (2007)

Hepatitis C virus (HCV) is a common blood-borne pathogen that relies heavily on nucleic acid testing for confirmation of infection. Nucleic acid tests are invaluable for the diagnosis of HCV infection and provide critical prognostic information for guiding treatment and measuring the response to antiviral therapy.To review the currently available molecular diagnostic tests for HCV, their clinical applications, and how these tests shed light on the natural history of HCV.Search of MEDLINE (1966 to July 2006), article reference lists, and national meeting abstracts for the diagnosis and applications of molecular diagnostic tests for HCV. Studies were selected on the basis of clinical relevance.Qualitative nucleic acid tests have low limits of detection (<50 IU HCV RNA/mL) and are used for confirmation of HCV infection and for screening blood donations. Hepatitis C virus genotype test results provide important prognostic information related to therapeutic response and are routinely used for selecting treatment regimens. Quantitative HCV RNA testing provides prognostic information regarding likelihood of treatment response and plays an important role in monitoring the antiviral response to treatment. Sustained virological response is defined as testing negative for HCV RNA 6 months after cessation of therapy. Recent studies suggest that the rate of response to therapy is also important. For example, conversion to an HCV RNA negative test result after 4 weeks of therapy constitutes a rapid virological response and is a strong predictor of treatment success. Patients who have not had an early virological response, defined as at least a 2-log decline in HCV RNA after 12 weeks of therapy, are unlikely to respond with an additional 36 weeks of therapy, and should stop therapy.A sensitive nucleic acid test should be used to confirm all cases of acute or chronic HCV infection. A genotype test and quantitative HCV RNA test should be performed on all patients prior to therapy to best assess probability of response and to aid in selection of appropriate therapeutic regimen. Monitoring HCV RNA during treatment provides important information on likelihood of sustained virological response. The same type of quantitative HCV RNA test should be used throughout a patient's treatment course.
Treating stroke: home or hospital?
Authors: G Mulley, T Arie
Journal: BMJ (1978)

A family doctor with an average list will see five or six new victims of stroke each year.'How is he to decide whether to treat the patient at home or refer him to hospital ?The World Health Organisation2 has stated that stroke is a medical emergency which requires accurate diagnosis and optimum care and that this can best be given in hospital.The United
Mechanism of T cell tolerance induction by murine hepatic Kupffer cells
Authors: Qiang You, Linling Cheng, Ross M. Kedl, Cynthia Ju
Journal: Hepatology (2008)

Abstract The liver is known to favor the induction of immunological tolerance rather than immunity. Although Kupffer cells (KC) have been indicated to play a role in liver tolerance to allografts and soluble antigens, the mechanisms involved remain unclear. We hypothesized that KCs could promote immune tolerance by acting as incompetent antigen-presenting cells (APC), as well as actively suppressing T cell activation induced by other potent APCs. The expression of antigen presentation-related molecules by KCs was phenotyped by flow cytometry. The abilities of KCs to act as APCs and to suppress T cell activation induced by splenic dendritic cells (DC) were examined by in vitro proliferation assays using CD4+ OVA-TCR (ovalbumin T cell receptor) transgenic T cells. We found that, compared with DCs, KCs expressed significantly lower levels of major histocompatibility complex (MHC) II, B7-1, B7-2, and CD40. This result is consistent with our observation that KCs were not as potent as DCs in eliciting OVA-specific T cell proliferation. However, KCs isolated from polyinosinic:polycytidylic acid–treated mice expressed significantly higher levels of MHC II and costimulatory molecules than did naïve KCs and could stimulate stronger T cell responses. More importantly, we found that KCs could inhibit DC-induced OVA-specific T cell activation. Further investigation of the underlying mechanism revealed that prostaglandins produced by KCs played an important role. The results ruled out the possible involvement of interleukin-10, nitric oxide, 2,3-dioxygenase, and transforming growth factor β in KC-mediated T cell suppression. Conclusion: Our data indicate that KCs are a tolerogenic APC population within the liver. These findings suggest that KCs may play a critical role in regulating immune reactions within the liver and contributing to liver-mediated systemic immune tolerance. (Hepatology 2008.)
Mapping TB resistance
Authors: Nicole LeBrasseur
Journal: The Journal of Experimental Medicine (2009)

The first genetic resistance factor for tuberculosis (TB) infection is now reported by Cobat et al. The group has identified one locus that determines whether an individual will respond to the TB skin test and a second that controls the extent of that response. The results suggest that one major genetic locus controls innate resistance to the pathogen in humans.

Two-thirds of the global population is infected with Mycobacterium tuberculosis, the agent responsible for TB. Yet the disease only manifests in about 10% of infected individuals. To find genetic variants controlling susceptibility to infection, the authors studied 128 families in Cape Town, South Africa, where TB is highly endemic.

Although most subjects were likely to have been exposed to M. tuberculosis, about 40% did not show delayed type hypersensitivity (DTH) in a skin antigen test. This strong resistance mapped to a 6-Mbp chromosome region, 11p14. This locus may unveil cellular mechanisms that might one day be manipulated to prevent TB—an important goal given the recent rise in drug-resistant strains.

The second locus, in the 2.9-Mbp 5p15 region, segregated with differing extents of positive DTH responses. These genetic factors might contribute to whether an infected individual keeps the bacterium dormant or develops the disease. The same chromosomal region is associated with susceptibility to sarcoidosis, an immune disorder of persistent inflammation that is often associated with TB.

A candidate 5p15 gene is a solute carrier (SLC) family member. A human SLC member called NRAMP1 is known to influence granuloma responses to mycobacteria, and loss of the mouse SLC6A3 protein reduces DTH response to ovalbumin. NL
Do Worldwide Outbreaks Mean Tuberculosis Again Becomes 'Captain of All These Men of Death'?
Authors: Charles Marwick
Journal: JAMA (1992)

THE ADMINISTRATION, public health community, and Congress all are trying to head off the spread of multidrug-resistant tuberculosis in the United States. Many reports of the resistant form of the organism have been linked with those who are infected with the human immunodeficiency virus (HIV). As the problem grows, President George Bush is nearly doubling the request for funds for tuberculosis elimination to $40 million this year. In Congress, Sen Edward Kennedy (D, Mass) is requesting funds to study issues raised by the occurrence of this resistant form and its association with HIV. Drug-resistant tuberculosis also is being reported around the world, especially in developing countries, says Barry Bloom, PhD, Albert Einstein College of Medicine, New York, NY. Resistance has emerged, he says, because antituberculosis drugs were freely distributed in some countries without controls over their use. <h3>System Failure?</h3> In the United States in the years prior to 1984, about
Methodological and Policy Limitations of Quantifying the Saving of Lives: A Case Study of the Global Fund's Approach
Authors: David McCoy, Nele Jensen, Katharina Kranzer, Rashida A. Ferrand, Eline L. Korenromp
Journal: PLoS Medicine (2013)

David McCoy and colleagues critique the dominance of "lives saved" models of assessing the impact of health programs, using The Global Fund as a case study. Please see later in the article for the Editors' Summary
Vaccine-specific T-cell proliferation in response to a dual peptide cancer vaccine in breast and ovarian cancer patients
Authors: Erika J Schneble, John S Berry, Alfred F Trappey, Timothy J Vreeland, Diane F Hale, Alan K Sears, Guy T Clifton, Sathibalan Ponniah, Nathan M Shumway, Elizabeth A Mittendorf, George E Peoples
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts HER2 is a commonly expressed tumor-associated antigen in breast (BrCa) and, therefore, an attractive target for immunotherapy. We have investigated HER2-derived peptides as vaccines mixed with GM-CSF to include GP2 (a HLA-A2 and HLA-A3 restricted, CD8+ eliciting epitope) and AE37
Mental disorders in public, private nonprofit, and proprietary general hospitals
Authors: M Olfson, D Mechanic
Journal: American Journal of Psychiatry (1996)

The authors' goal was to assess the effects of facility ownership on the characteristics of psychiatric inpatients treated in public, private nonprofit, or proprietary general hospitals.Data from the 1993 National Hospital Discharge Survey were analyzed to determine the number, sociodemographic and diagnostic composition, and treatment characteristics of patients with primary mental disorders discharged from public, private nonprofit, and proprietary general hospitals.An estimated 1.83 million patients with a primary mental disorder diagnosis were discharged from general hospitals in 1993; the number of such discharges in the National Hospital Discharge Survey, which excluded federal general hospitals, was 13,086. These patients were unevenly distributed among public (9.4%), private nonprofit (78.9%), and proprietary (11.7%) hospitals. Psychiatric patients of public and private nonprofit hospitals were more likely to be diagnosed with schizophrenia (public: 23.4%, nonprofit: 18.8%, proprietary: 12.6%), a comorbid substance-related disorder (public: 29.9%, nonprofit: 31.0%, proprietary: 17.4%), a personality disorder (public: 11.6%, nonprofit: 11.3%, proprietary: 4.7%), or a general medical disorder (public: 62.4%, nonprofit: 57.4%, proprietary: 41.1%) than patients of proprietary hospitals. Uninsured psychiatric patients were far more common at public hospitals than at the other types of facilities (public: 17.0%, nonprofit: 9.9%, proprietary: 6.4%).Public general hospitals play an important role in caring for uninsured patients with severe mental illness. Before widespread closures occur in the public general hospital sector, it is critical that policy makers identify and develop resources to replace the care these institutions currently provide to poor patients with severe psychiatric disorders.
Friction Injuries Following Road Accidents
Authors: C. C. Slack
Journal: BMJ (1952)

THROMBOSIS IN VARICOSE VEINS 1MJO Discussion Raeburn (1951) has restated the initiating causes of thrombosis as (a) venous stasis; (b) disordered metabolism of vascular endothelium, leading possibly to increased adhesiveness -(c) intimal trauma; and (d) sepsis.Venous stasis would certainly result from partial occlusion by a foreign body.The presence of aseptic inflammation has been shown by vein biopsy.Intimal damage may occur from repeated small traumata produced by limb movements with a foreign body in the vein lumen.Some of the criteria, therefore, for the production of venous thrombosis appear to be satisfied.Clinical implications of the method are obvious.The relation of the method to other forms of treatment has yet to be determined.A more definite assessment awaits the progress of adequate follow-up studies. SummaryA new method of causing intravascular thrombosis is presented, with particular reference to the treatment of varicose veins.It consists in leaving a length of silk ligature within the lumen of the vein.Clinical and histological evidence is produced to show that complete obliteration of the vein invariably results without any ill effects, general or local.The mechanism and clinical implications of the method are discussed.
Acquired Partial Corticosterone Methyl Oxidase Type II Defect in Diabetes Mellitus: Case of Hyperreninemic Hypoaldosteronism
Authors: Susan S Braithwaite, Anthony L Barbato, Mary Ann Emanuele
Journal: Diabetes Care (1990)

The aim of this study was to investigate the pathogenesis of hypoaldosteronism in diabetes. Endogenous elevation of plasma renin activity and exogenous corticotropin were used to study steroidogenesis. Observations were made over 12 yr on the evolution and treatment of hyperkalemia in a diabetic subject. In 1977, potassium, baseline cortisol, aldosterone, and renin activity were normal; renin activity increased normally with posture; and cortisol responded normally to ACTH infusion. Nine yr later, persistent hyperkalemia was documented. Upright renin activity was elevated to 5.26 ng · L−1 · s−1, with concomitant elevation of 18-hydroxycorticosterone (18-OHB) and a low-normal aldosterone level. One hour after administration of 0.25 mg i.m. cosyntropin, cortisol increased normally, aldosterone increased from 220 to 360 pM, and 18-OHB increased from 3700 to 4800 pM. During treatment with fludrocortisone, fludrocortisone with furosemide, and furosemide alone, improvement of hyperkalemia was noted. Endogenous hyperreninemia and basal elevations of 18-OHB, accompanied by limited aldosterone responsiveness to renin and ACTH, suggest the presence of a partial corticosterone methyl oxidase type II defect. Evolution of hyperkalemia between 1977 and 1986 suggests this defect was acquired.
THE WATER SUPPLY IN SHIPS FROM ITS BEGINNING TO THE PRESENT TIME.
Authors: HENRY G. BEYER
Journal: JAMA (1905)

The problem of the water supply for sea-going ships is one of the most important and, at the same time, one of the most difficult to solve of all the problems of naval hygiene. It certainly is not a simple question. Ships can not always choose the source of their water supply. It may be impure or even infected to begin with. But even granting that it was faultless when collected, it may not remain wholesome during a long cruise. The early efforts of the old sanitarians to provide faultless drinking water for seamen are full of pathos. Before the last century men did not know in what wholesome drinking water consisted. Much less did they know how to preserve it pure and sweet. When in addition to the ignorance of the age we find all efforts toward progress met either with cold indifference or active opposition, we may easily
Bile duct injury after laparoscopic cholecystectomy: the value of endoscopic retrograde cholangiopancreatography.
Authors: P H Davids, J Ringers, E A Rauws, L T de Wit, K Huibregtse, M N van der Heyde, G N Tytgat
Journal: Gut (1993)

This study describes the value of endoscopic retrograde cholangiopancreatography (ERCP) in patients with bile duct injury after laparoscopic cholecystectomy. Twelve consecutive patients were studied over a one year period. In all patients the biliary tree was visualised during ERCP. Four patients had complete bile duct obstruction, seven patients had a stricture (two with concomitant leakage), and one patient had leakage from a hepatic branch. Three patients with complete obstruction, presented with a relatively prolonged symptom free, 'silent' period before diagnosis. In all four patients with complete transection, a proximal hepaticojejunostomy was performed. In one patient with a tough fibrous stricture, secondary to incorrect clip placement, passage of the guidewire was impossible, leaving surgical reconstruction as the only therapeutic option. All remaining seven patients with leakage or strictures, or both were successfully treated by endoscopic sphincterotomy only (n = 1) or sphincterotomy and subsequent stent placement (n = 6). When patients do not recover uneventfully after laparoscopic cholecystectomy even without cholestasis or jaundice, early ERCP is recommended as a safe and valuable method to detect bile duct injury and to suggest treatment. Subsequently, more than half of such patients can be treated endoscopically. Extended follow up is needed to evaluate the longterm results.
521. Spliceosome-Mediated RNA Trans-Splicing with rAAV Partially Restores CFTR Function to Polarized Human CF Airway Epithelial Cells
Authors: Xiaoming Liu, Meihui Luo, Liang N. Zhang, Ziying Yan, Wei Ding, Roman Zak, Gary S. Mansfield, Lloyd G. Mitchell, John F. Engelhardt
Journal: Molecular Therapy (2005)

Top of pageAbstract
We previously reported that Spliceosome-Mediated RNA Trans-splicing (SMaRT) using recombinant adenoviral vectors expressing pre-trans-splicing molecules (PTMs) could partially restore CFTR chloride channel activity to polarized human |[Auml]|F508 CF airway epithelia. Although these studies proved that SMaRT could correct CFTR mRNA defects, recombinant adenoviral infection from the basolateral surface was required due to inefficient infection from the apical membrane. Hence, applications of SMaRT technology for CF gene therapy require further testing with alternative, more clinically viable, vector systems. Furthermore, since rAAV vectors have packing limitations with respect to the size of the CFTR transgene insert, SMaRT correction of CFTR has the added attraction of a smaller transgene cassette. In the present study, we investigated whether rAAV vectors could effectively rescue CFTR chloride conductance in polarized human CF airway epithelial cells using a SMaRT approach. AAV vectors were generated to contain a PTM engineered to bind intron 9 of CFTR pre-mRNA and then trans-splice the normal sequence for human CFTR exons 10-24 into the endogenous pre-mRNA. Human CF polarized airway epithelia were infected from the apical membrane with rAAV2 or rAAV5 CFTR-PTM vectors in the presence of proteasome-modulating agents (Doxorubicin and LLnL) to enhance transduction. Epithelia were then evaluated for cAMP-sensitive short circuit currents at 2 weeks post-infection. Levels of CFTR correction seen with rAAV2 (1.07 |[plusmn]| 0.24 micro-Amps) and rAAV5 (0.90 |[plusmn]| 0.20 micro-Amps) CFTR-PTM vectors were similar, representing a conductance equivalent to 14.2% and 13.6% of that observed in non-CF human polarized epithelia, respectively. RT-PCR analysis demonstrated the existence of wild type CFTR transcript in CFTR-PTM correct epithelia, while only the |[Delta]|F508 mRNA was detected in polarized cells infected with control rAAV LacZ-PTM vectors. These results provided evidence that rAAV vectors are capable of utilizing SMaRT for correction of CFTR function following apical infection of human CF airway epithelia. The ability of CFTR-PTM-mediated correction to maintain endogenous CFTR regulation of the transgene product may further improve the efficacy of gene therapy for CF.
High-performance PEGylated Mn–Zn ferrite nanocrystals as a passive-targeted agent for magnetically induced cancer theranostics
Authors: Jun Xie, Yu Zhang, Caiyun Yan, Lina Song, Song Wen, Fengchao Zang, Gong Chen, Qi Ding, Changzhi Yan, Ning Gu
Journal: Biomaterials (2014)