tbuckley/cabot-search huggingface dataset:
Pulmonary Embolism by Small Blood Clots: Physiological Responses in the Anaesthetized Dog
Authors: R. Marshall, P. R. Allison
Journal: Thorax (1962)

Embolization ofthepulmonary arteries of anaesthetized dogsbylarge blood clots orthrombi usually causes nodisturbance ofheart rhythmor ofrespiration atthetimeofimpaction ofthe embolus (Allison, Dunnill, andMarshall, 1960; Marshall, Allison, Sabiston, Bosman, andDunnill, inpreparation) andconsiderable recovery oflung function occurs during thefirst twoweeksafter theembolization. Itispossible thathuman pulmonary embolism ofsevere degree isdueto theimpaction ofalarge embolus after multiple small emboli havecaused aninitial partial obstructionofthepulmonary circulation. Experimental workinanimals alsosuggests thatembolism of small arteries, rather thanlarge arteries, initiates reflexes whichmay increase thepulmonary vascular resistance andcause evenmoreobstructiontothecirculation. Thepresent investigation wascarried outto observe therespiratory andhaemodynamic effects ofrepeated embolism bysmall bloodclots andthe recovery offunction after theembolization. METHODS The material usedforembolization in these experiments wasfresh bloodclot.Thedogswere premedicated withmorphine, 1.1mg/kg.,and chlorpromazine, 1.0mg./kg., andanaesthetized with pentobarbitone. The dogswerebledintosterile beakers, thebloodforeachinjection beingina separate beaker.Thebloodwasallowed tostand until ithadformed afirmclot whichwasthenchopped withsterile scissors, poured into asyringe, andinjected slowly intravenously. Insomeexperiments theblood wasinjected intotheforeleg veinthrough a thinwalled 18gaugeneedle andinothers itwasinjected through a polythene tubeinserted byway ofthe femoral veinintotheinferior venacava. Theinternal diameter ofbothneedle andtubewas1mm. Before theclots wereinjected thefunctional residual capacity (F.R.C.) anddiffusing capacity ofthelungs weremeasured (Marshall etal., inpreparation) and cardiac catheterization wascarried outtomeasurethe pulmonary arterial pressure. Inmostofthedogsthe catheter wasleft inthemainpulmonary artery during theinjection oftheclots. Cannulae wereinserted intotheleft femoral artery forrecording pressure, intotheright femoral artery forwithdrawing blood, intothesuperior venacavaformeasuring central venouspressure, andintotheright femoral veinfor theinjection ofdyeandbloodclots. A cuffed endotracheal tubewasinserted andrespiration was recorded using aspirometer andkymograph. Inmost oftheexperiments thedogsbreathed airenriched with oxygenbutintheexperiments wheretheright-to-left shunt wasmeasured (seebelow) thespirometer contained 100%oxygenandthedog's lungs werewashed outwithoxygenbefore connexion tothespirometer. An intra-oesophageal balloon connected toa capacitancemanometer wasusedtomeasureintrathoracic pressure, andtheoutput fromthis manometer, together witha volumetracing obtained froma lowtorque potentiometer attached to thespirometer, were
Two-Center Evaluation of Dynamic Sentinel Node Biopsy for Squamous Cell Carcinoma of the Penis
Authors: Joost A.P. Leijte, Ben Hughes, Niels M. Graafland, Bin K. Kroon, Renato A. Valdés Olmos, Omgo E. Nieweg, Cathy Corbishley, Sue Heenan, Nick Watkin, Simon Horenblas
Journal: Journal of Clinical Oncology (2009)

Sentinel node biopsy is used to evaluate the nodal status of patients with clinically node-negative penile carcinoma. Its use is not widespread, and the majority of patients with clinically node-negative disease undergo an elective inguinal lymph node dissection. Reservations about the use of sentinel node biopsy include the fact that most current results come from one institution and the supposedly long learning curve associated with the procedure. The purpose of this study was to address these issues by analyzing results from two centers and by evaluating the learning curve.All patients undergoing sentinel node biopsy for penile carcinoma at two centers were included. The sentinel node identification rate, false-negative rate, and morbidity of the procedure were calculated.from the first 30 procedures were assessed for a potential learning curve. Results A total of 323 patients with penile squamous cell carcinoma, which included 611 clinically node-negative groins, were scheduled for sentinel node biopsy. A sentinel node was found in 572 of the 592 groins (97%) that proceeded to sentinel node biopsy. In 79 groins, a sentinel node was positive for tumor. Six inguinal node recurrences occurred after a negative sentinel node procedure, all within 15 months after sentinel node biopsy. The combined false-negative rate was 7%. Complications occurred in 4.7% of explored groins. None of the false-negative procedures occurred in the initial 30 procedures.Sentinel node biopsy is a suitable procedure to stage clinically node-negative penile cancer, and it has a low complication rate. No learning curve was demonstrated in this study.
NKT cells reject islets
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

TIM-2 soaks up ferritinThe TIM (T cell immunoglobulin mucin) proteins have emerged as key regulators of allergic and autoimmune diseases due to their influence on T helper (Th)-1 and Th-2 responses.On page 955, Chen and colleagues show that one member of this family, TIM-2, multitasks as a receptor for H-ferritin, a component of the iron storage protein ferritin.Ferritin was not what the group expected to find when they launched a search for TIM-2 ligands."Ferritin is not something immunologists think about much," says senior author William Seaman.Although circulating H-ferritin had been shown to increase during inflammation and to bind to T and B cells, the consequences of these observations were largely unknown.Chen et al. now show that although TIM-2 is most highly expressed in the liver, the primary iron storage organ, this protein is also found on splenic B cells.TIM-2 expression was particularly high on germinal center B cells that were actively responding to antigenic stimulation.Using a TIM-2 reporter cell line, they showed that a soluble product of activated macrophages bound to TIM-2.That product was H-ferritin.Binding triggered endocytosis of the receptor-ligand pair, suggesting that the interaction was functional.The authors are now investigating the consequences of the ferritin-TIM-2 interaction.A recent study showed that intracellular H-ferritin is required for the antiapoptotic effect of NF-B activation in fibroblasts, prompting Seaman to speculate that H-ferritin uptake in activated germinal center B cells might have a similar antiapoptotic effect.
Development of Risk-Based Guidelines for Pediatric Cancer Survivors: The Children's Oncology Group Long-Term Follow-Up Guidelines From the Children's Oncology Group Late Effects Committee and Nursing Discipline
Authors: Wendy Landier, Smita Bhatia, Debra A. Eshelman, Katherine J. Forte, Teresa Sweeney, Allison L. Hester, Joan Darling, F. Daniel Armstrong, Julie Blatt, Louis S. Constine, Carolyn R. Freeman, Debra L. Friedman, Daniel M. Green, Neyssa Marina, Anna T. Meadows, Joseph P. Neglia, Kevin C. Oeffinger, Leslie L. Robison, Kathleen S. Ruccione, Charles A. Sklar, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2004)

The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers are risk-based, exposure-related clinical practice guidelines intended to promote earlier detection of and intervention for complications that may potentially arise as a result of treatment for pediatric malignancies. Developed through the collaborative efforts of the Children’s Oncology Group Late Effects Committee, Nursing Discipline, and Patient Advocacy Committee, these guidelines represent a statement of consensus from a multidisciplinary panel of experts in the late effects of pediatric cancer treatment. The guidelines are both evidence-based (utilizing established associations between therapeutic exposures and late effects to identify high-risk categories) and grounded in the collective clinical experience of experts (matching the magnitude of risk with the intensity of screening recommendations). They are intended for use beginning 2 or more years following the completion of cancer therapy; however, they are not intended to provide guidance for follow-up of the survivor’s primary disease. A complementary set of patient education materials (“Health Links”) was developed to enhance follow-up care and broaden the application of the guidelines. The information provided in these guidelines is important for health care providers in the fields of pediatrics, oncology, internal medicine, family practice, and gynecology, as well as subspecialists in many fields. Implementation of these guidelines is intended to increase awareness of potential late effects and to standardize and enhance follow-up care provided to survivors of pediatric cancer throughout the lifespan. The Guidelines, and related Health Links, can be downloaded in their entirety at www.survivorshipguidelines.org .
Dietary Fat Reduction and Breast Cancer Outcome: Interim Efficacy Results From the Women's Intervention Nutrition Study
Authors: Rowan T. Chlebowski, George L. Blackburn, Cynthia A. Thomson, Daniel W. Nixon, Alice Shapiro, M. Katherine Hoy, Marc T. Goodman, Armando E. Giuliano, Njeri Karanja, Philomena McAndrew, Clifford Hudis, John Butler, Douglas Merkel, Alan Kristal, Bette Caan, Richard Michaelson, Vincent Vinciguerra, Salvatore Del Prete, Marion Winkler, Rayna Hall, Michael Simon, Barbara L. Winters, Robert M. Elashoff
Journal: JNCI Journal of the National Cancer Institute (2006)

Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer receiving conventional cancer management.A total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40:60 to dietary intervention (n = 975) or control (n = 1462) groups. An interim analysis was performed after a median follow-up of 60 months when funding for the intervention ceased. Mean differences between dietary intervention and control groups in nutrient intakes and anthropometric variables were compared with t tests. Relapse-free survival was examined using Kaplan-Meier analysis, stratified log-rank tests, and Cox proportional hazards models. Statistical tests were two-sided.Dietary fat intake was lower in the intervention than in the control group (fat grams/day at 12 months, 33.3 [95% confidence interval {CI} = 32.2 to 34.5] versus 51.3 [95% CI = 50.0 to 52.7], respectively; P<.001), corresponding to a statistically significant (P = .005), 6-pound lower mean body weight in the intervention group. A total of 277 relapse events (local, regional, distant, or ipsilateral breast cancer recurrence or new contralateral breast cancer) have been reported in 96 of 975 (9.8%) women in the dietary group and 181 of 1462 (12.4%) women in the control group. The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 (95% CI = 0.60 to 0.98, P = .077 for stratified log rank and P = .034 for adjusted Cox model analysis). Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status.A lifestyle intervention reducing dietary fat intake, with modest influence on body weight, may improve relapse-free survival of breast cancer patients receiving conventional cancer management. Longer, ongoing nonintervention follow-up will address original protocol design plans, which called for 3 years of follow-up after completion of recruitment.
Calpain activation contributes to hyperglycaemia-induced apoptosis in cardiomyocytes
Authors: Y. Li, Y. Li, Q. Feng, M. Arnold, T. Peng
Journal: Cardiovascular Research (2009)

Cardiomyocyte apoptosis contributes to cardiac complications of diabetes. The aim of this study was to investigate the role of calpain in cardiomyocyte apoptosis induced by hyperglycaemia. In cultured adult rat ventricular cardiomyocytes, high glucose (33 mM) increased calpain activity and induced apoptosis, concomitant with the impairment of Na+/K+ ATPase activity. These effects of high glucose on cardiomyocytes were abolished by various pharmacological calpain inhibitors, knockdown of calpain-1 but not calpain-2 using siRNA, or over-expression of calpastatin, a specific endogenous calpain inhibitor. The effect of calpain inhibition on cardiomyocyte apoptosis was abrogated by ouabain, a selective inhibitor of Na+/K+ ATPase. Furthermore, blocking gp91phox-NADPH oxidase activation, L-type calcium channels, or ryanodine receptors prevented calpain activation and apoptosis in high glucose-stimulated cardiomyocytes. In a mouse model of streptozotocin-induced diabetes, administration of different calpain inhibitors blocked calpain activation, increased the Na+/K+ ATPase activity, and decreased apoptosis in the heart. Calpain-1 activation induces apoptosis through down-regulation of the Na+/K+ ATPase activity in high glucose-stimulated cardiomyocytes and in vivo hyperglycaemic hearts. High glucose-induced calpain-1 activation is mediated through the NADPH oxidase-dependent pathway and associated with activation of L-type calcium channels and ryanodine receptors. Our data suggest that calpain activation may be important in the development of diabetic cardiomyopathy and thus may represent a potential therapeutic target for diabetic heart diseases.
Penicillin for Ocular Infections
Authors: G. T. W. Cashell
Journal: BMJ (1944)

The use of penicillin in ophthalmology has led to the rapid and successful treatment of many acute bacterial infections, and the risk of intraocular.infection following injuries has been lessened.The following report of a series of cases treated with this drug at an R.A.F.hospital is presented in substantiation of these remarks.Before giving details of the cases it is necessary to outline briefly: (1) the principles of the treatment; (2) the types of ocular infection suitable for treatment; (3) the methods of application and dosage; (4) the assessment of the results. Principles of TreatmentPenicillin is admirably suited for surface application, and can be used in the form of drops in ophthalmic work.It is found that only small quantities need be employed: doses in the order of 1,000 units are sufficient to treat many cases.The drug has been used in the form of the calcium or sodium salt; both have been well tolerated in the eyes, and have been
Antibiotic therapy reduces nitrosative stress and programmed cell death in the rabbit foetal lung
Authors: C. Gras-Le Guen, A. Jarry, G. Vallette, C. Toquet, C. Colombeix, C. L. Laboisse, G. Potel, J-C. Roze, D. Bugnon, T. Debillon
Journal: European Respiratory Journal (2005)

The correlation of clinical and epidemiological data suggests that intrauterine infection/inflammation can promote foetal lung injury. The aim of this study was: 1) to characterise the early inflammatory response elicited in infected foetal lungs, in terms of nitric oxide-derived oxidative stress and programmed cell death; and 2) to investigate the effects of antibiotic therapy on these parameters. A previously described rabbit experimental model of materno-foetal infection was used. Animals were divided into three groups: controls; Escherichia coli infected (12 h); and E. Coli infected (12 h) and treated (24 h gentamicin+ceftriaxone). Foetal lungs were examined in terms of histology, nitric oxide synthase (NOS) activity, immunohistochemical detection of 3-nitrotyrosine, and detection of apoptotic cells by the TUNEL assay and Hoechst staining. In the infected group, a moderate inflammatory response was observed, associated with a significant increase in inducible NOS activity, the formation of 3-nitrotyrosine residues in epithelial and immune cells, the down-regulation of constitutive NOS activity and clusters of apoptotic cells, as compared with the control group. Early antibiotic therapy, initiated at 12 h post-inoculation, elicited a significant decrease in the infection-induced nitrosative stress. Levels of 3-nitrotyrosine and of apoptotic cells were decreased in the infected-and-treated group compared with the infected group, mainly by the re-expression of constitutive NOS and of the basal level of inducible NOS. Altogether, these findings indicate that early antibiotic therapy can curb the inflammatory reaction and help avert antenatal lung injury, which is known to be involved in the onset of bronchopulmonary dysplasia.
The Demanding Patient Revisited—Reply
Authors: Keerthi Gogineni, Katherine L. Shuman, Nicole B. Gabler, Ezekiel J. Emanuel
Journal: JAMA Oncology (2015)

from Memorial Sloan Kettering Cancer Center for their comments concerning the definition of "actionability" in the setting of cancer presenting as CUP.Also, in response to Varghese and Saltz, TTF1-positive tumors with EML4-ALK fusions characteristic of non-small-cell lung cancer were not included in our series.One case in our series did feature a TMPRSS-ERG fusion diagnostic of metastatic prostatic carcinoma.This case was listed as a CUP in that the tumor did not mark by IHC analysis as being of prostatic origin and the clinical workup did not suggest that the patient had prostate cancer.Although not a focus of our present study, we believe that hybrid capture-based comprehensive genomic profiling can definitively identify the site of origin in approximately 10% to 15% of CUP cases.The case example in our article of an EML4-ALK fusion cancer responding dramatically to crizotinib therapy cannot, in our opinion, be designated as a lung cancer by current diagnostic criteria because IHC analysis was negative for TTF1, positive for vimentin, and featured a poorly differentiated, nonmucinous, sarcomatoid morphologic appearance.Finally, we thank Whang and Hayes from the University of North Carolina for their letter describing the prolonged response of a patient to an anti-human epidermal growth factor receptor 2 plus chemotherapy regimen for an ERBB2-amplified CUP.Finally, our article 1 and all 3 Letters to the Editor have in common the desire to see the development of mechanism-driven prospective clinical trials in which genomic profiling is used to search for "druggable" alterations in CUP cases to achieve a comparison of the results of the use of targeted therapies when possible with generic chemotherapy and testing whether this approach can improve the clinical outcomes for patients with this devastating form of cancer.
VACCINE SHORTAGES: History, Impact, and Prospects for the Future
Authors: Alan R. Hinman, Walter A. Orenstein, Jeanne M. Santoli, Lance E. Rodewald, Stephen L. Cochi
Journal: Annual Review of Public Health (2005)

Vaccine shortages can result from higher-than-expected demand, interruptions in production/supply, or a lack of resources to purchase vaccines. Each of these factors has played a role in vaccine shortages in the United States during the past 20 years. Since 2000, the United States has experienced an unprecedented series of shortages of vaccines recommended for widespread use against 9 diseases, after more than 15 years without vaccine supply problems. In developing countries, the major cause of vaccine shortages is lack of resources to purchase them. Although there are several steps that could reduce the likelihood of future vaccine shortages, many would take several years to implement. Consequently, we will probably continue to see occasional shortages of vaccines in the United States in the next few years.
Schistosomiasis Control: Past, Present, and Future
Authors: P. Jordan, P. L. Rosenfield
Journal: Annual Review of Public Health (1983)

In this paper we review the range of control measures presently available and highlight the most promising control strategies both disease-specific and nonspecific. We also discuss the technical measures in relation to practical use in the field. We describe developments in epidemiological techniques for investigating the extent of the disease problem and for monitoring and evaluating control activities. We review briefly the experiences of national and international control and research programs to demonstrate some key characteristics that need to be considered in undertaking control. In the conclusion we suggest future prospects for the control of schistosomiasis.  (excerpt)
Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice.
Authors: F D Finkelman, A Svetic, I Gresser, C Snapper, J Holmes, P P Trotta, I M Katona, W C Gause
Journal: The Journal of Experimental Medicine (1991)

Antigens and infectious agents that stimulate interferon alpha(IFN-alpha) production in mice induce antibody responses that are predominantly of the immunoglobulin (Ig)G2a isotype and contain little or no IgE. This suggested the possibility that IFN-alpha might have a role in directing Ig isotype selection. Consistent with this possibility, we have found that injection of mice with recombinant mouse IFN-alpha suppresses IgE secretion, enhances IgG2a secretion, and has no independent effect on IgG1 secretion in mice stimulated with a foreign anti-IgD antibody. Injection of mice with polyinosinic acid.polycytidylic acid (poly I.C), an inducer of macrophage IFN-alpha production, also suppresses the anti-IgD antibody-induced IgE response and stimulates the IgG2a response; these effects are blocked by a sheep antibody that neutralizes mouse IFN-alpha/beta. Both recombinant IFN-alpha and poly I.C have maximum IgE suppressive and IgG2a stimulatory effects when injected early in the anti-IgD antibody-induced immune response. Addition of IFN-alpha to mouse B cells cultured with lipopolysaccharide (LPS) + interleukin 4 (IL-4) suppresses both IgG1 and IgE production, but much less potently than IFN-gamma. IFN-alpha suppresses anti-IgD antibody-induced increases in the level of splenic IL-4 mRNA, but enhances the anti-IgD antibody-induced increase in the splenic level of IFN-gamma mRNA. These results are consistent with the effect of IFN-alpha on Ig isotype expression in mice, as IL-4 stimulates IgE and suppresses IgG2a secretion while IFN-gamma exerts opposite effects. These observations suggest that antigen presenting cells, by secreting IFN-alpha early in the course of an immune response, can influence the nature of that response both through direct effects on B cells and by influencing the differentiation of T cells.
Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine
Authors: Martin Dichgans, Tobias Freilinger, Gertrud Eckstein, Elena Babini, Bettina Lorenz-Depiereux, Saskia Biskup, Michel D Ferrari, Jürgen Herzog, Arn MJM van den Maagdenberg, Michael Pusch, Tim M Strom
Journal: The Lancet (2005)