tbuckley/cabot-search huggingface dataset:
Association of specific immune response to pork and beef insulin with certain HLA-DR antigens in type 1 diabetes.
Authors: I Sklenar, T M Neri, W Berger, P Erb
Journal: BMJ (1982)

To test the association of HLA-DR antigens with high-responder and low-responder status to either beef or pork insulin, insulin antibodies in diabetic sera were separated into those with average low and those with average high affinity and their insulin-binding capacities for each insulin determined. Significantly less binding of pork insulin by the high affinity antibodies occurred in the group of patients with DR3 antigens compared with those with DR4 antigens (p less than 0.01) and DR3/4 antigens (p less than 0.01). The difference in the binding capacity of beef insulin by the high affinity antibodies between the groups with DR3 and DR4 antigens was less pronounced but still significant. The high-responder status of DR3/4 antigens to pork insulin suggests that the gene or genes associated with HLA-DR4, and responsible for a high response to pork insulin, are dominant to genes associated with HLA-DR3 and a low response. If extended to human insulin and different HLA-DR and HLA-B antigen patterns, these finding should help in the therapeutic selection of the appropriate insulin and thus reduce the induction of an anti-insulin response in patients with diabetes.
Cases of Attempted Suicide in a General Hospital: A Problem in Social and Psychologic Medicine
Authors: Merrill Moore
Journal: New England Journal of Medicine (1937)

Original Article from The New England Journal of Medicine — Cases of Attempted Suicide in a General Hospital: A Problem in Social and Psychologic Medicine — A Report on a Local Condition, Including a Survey of 1,147 Records of Attempted Suicide Cases Admitted to the Boston City Hospital
Piperlongumine treatment inactivates peroxiredoxin 4, exacerbates endoplasmic reticulum stress, and preferentially kills high-grade glioma cells
Authors: Tae Hyong Kim, Jieun Song, Sung-Hak Kim, Arav Krishnavadan Parikh, Xiaokui Mo, Kamalakannan Palanichamy, Balveen Kaur, Jianhua Yu, Sung Ok Yoon, Ichiro Nakano, Chang-Hyuk Kwon
Journal: Neuro-Oncology (2014)

Piperlongumine, a natural plant product, kills multiple cancer types with little effect on normal cells. Piperlongumine raises intracellular levels of reactive oxygen species (ROS), a phenomenon that may underlie the cancer-cell killing. Although these findings suggest that piperlongumine could be useful for treating cancers, the mechanism by which the drug selectively kills cancer cells remains unknown.We treated multiple high-grade glioma (HGG) sphere cultures with piperlongumine and assessed its effects on ROS and cell-growth levels as well as changes in downstream signaling. We also examined the levels of putative piperlongumine targets and their roles in HGG cell growth.Piperlongumine treatment increased ROS levels and preferentially killed HGG cells with little effect in normal brain cells. Piperlongumine reportedly increases ROS levels after interactions with several redox regulators. We found that HGG cells expressed higher levels of the putative piperlongumine targets than did normal neural stem cells (NSCs). Furthermore, piperlongumine treatment in HGG cells, but not in normal NSCs, increased oxidative inactivation of peroxiredoxin 4 (PRDX4), an ROS-reducing enzyme that is overexpressed in HGGs and facilitates proper protein folding in the endoplasmic reticulum (ER). Moreover, piperlongumine exacerbated intracellular ER stress, an effect that was mimicked by suppressing PRDX4 expression.Our results reveal that the mechanism by which piperlongumine preferentially kills HGG cells involves PRDX4 inactivation, thereby inducing ER stress. Therefore, piperlongumine treatment could be considered as a novel therapeutic option for HGG treatment.
A Quarter Century of Chemotherapy
Authors: George H. Hitchings
Journal: JAMA (1969)

A Passano Award, quite as much as John Donne's tolling bell, marks a time in which to pause and to reflect on the interdependence of humankind and of scientists and of scientific progress in particular. I wonder how many of you can recall the state of chemotherapy 30 years ago? At that time sulfanilamide was hailed as the "drug of the year" by Dr. Morris Fishbein, then editor ofThe Journal. As quoted by the<i>Boston Herald</i>on Dec 31, 1939, he said, "By repeated success, sulfanilamide established itself as one of medicine's few specifics, those remedies which are especially suited to cure certain diseases. The list includes quinine for malaria, arsphenine for syphilis, and diphtheria antitoxin." Sulfanilamide made four. Period. What I wish to discuss, however, is not the encouragement which that discovery gave to the search for specific remedies, but rather the conceptual advances that it stimulated. As
Proximity to Natural Gas Wells and Reported Health Status: Results of a Household Survey in Washington County, Pennsylvania
Authors: Peter M. Rabinowitz, Ilya B. Slizovskiy, Vanessa Lamers, Sally J. Trufan, Theodore R. Holford, James D. Dziura, Peter N. Peduzzi, Michael J. Kane, John S. Reif, Theresa R. Weiss, Meredith H. Stowe
Journal: Environmental Health Perspectives (2014)

Little is known about the environmental and public health impact of unconventional natural gas extraction activities, including hydraulic fracturing, that occur near residential areas.Our aim was to assess the relationship between household proximity to natural gas wells and reported health symptoms.We conducted a hypothesis-generating health symptom survey of 492 persons in 180 randomly selected households with ground-fed wells in an area of active natural gas drilling. Gas well proximity for each household was compared with the prevalence and frequency of reported dermal, respiratory, gastrointestinal, cardiovascular, and neurological symptoms.The number of reported health symptoms per person was higher among residents living < 1 km (mean ± SD, 3.27 ± 3.72) compared with > 2 km from the nearest gas well (mean ± SD, 1.60 ± 2.14; p = 0.0002). In a model that adjusted for age, sex, household education, smoking, awareness of environmental risk, work type, and animals in house, reported skin conditions were more common in households < 1 km compared with > 2 km from the nearest gas well (odds ratio = 4.1; 95% CI: 1.4, 12.3; p = 0.01). Upper respiratory symptoms were also more frequently reported in persons living in households < 1 km from gas wells (39%) compared with households 1-2 km or > 2 km from the nearest well (31 and 18%, respectively) (p = 0.004). No equivalent correlation was found between well proximity and other reported groups of respiratory, neurological, cardiovascular, or gastrointestinal conditions.Although these results should be viewed as hypothesis generating, and the population studied was limited to households with a ground-fed water supply, proximity of natural gas wells may be associated with the prevalence of health symptoms including dermal and respiratory conditions in residents living near natural gas extraction activities. Further study of these associations, including the role of specific air and water exposures, is warranted.
Service increment for teaching and research
Authors: D Plamping, A Towle
Journal: BMJ (1994)

the month after discharge the risk of suicide is increased over 100-fold.Approximately 2/8% of those presenting after parasuicide will have com- mitted suicide at eight year follow up.For those admitted to hospital the risk might be expected to be higher: 15% of patients admitted to hospital with depression commit suicide.3The introduction of more complex discharge procedures and the care programme approach have led to a greater concentration on patients who require admission to hospital and suffer severe mental illness.The lack of new resources to implement these time consuming procedures may lead to reduced provision for patients presenting in crisis.The lack of suicides in our cohort, despite important risk factors, illustrates the difficulties for secondary services in effectively targeting those at high risk of suicide.The Health of the Nation aims at reducing the rate of suicide by 15% overall and by 33% among people with serious mental illness.4In the absence of meaningful target groups, with limited and redirected resources we run the risk of targeting too specific a group, by default, and failing to meet those aims.
Decrease of Serum Cholesterol in Rabbits Following Chloroform Inhalation and as Diurnal Variation
Authors: M. ELAINE FEDOROFF, R. ALTSCHUL
Journal: Circulation Research (1958)

Normal rabbits were exposed to single, subanesthetitizing doses of chloroform vapors and a regular decrease in their total serum cholesterol was found. In rabbits with abnormally high serum cholesterol levels, however, no consistent changes were observed. In control experiments it was found that in the normal rabbit there is a diurnal variation in serum cholesterol, with lowest values around 4 p.m. No consistent changes were found in the serum cholesterol of rabbits after being submerged for brief periods in ice water.
Big strides in Europe towards clinical trial transparency
Authors: T. Groves
Journal: BMJ (2014)

The EMA, EU, and UK HRA usher in an age of evidence enlightenment

Two and half years ago several of Europe’s medicines regulators proposed that complete trial data on all drugs approved in the EU should be made publicly available in the best interests of public health.1 About time too, thought many advocates of research transparency, but would they really do it? Now we know that they will, despite attempts to derail their plans.2

The European Medicines Agency (EMA) decided on 2 October that, for all new centralised drug marketing authorisations submitted after 1 January 2015, it will provide public access to the core content of clinical study reports and will allow researchers to download and use the reports for further analyses.3 Members of the public will have to register to read the reports on screen, while academics and researchers must register and also provide proof of identity. The same policy will apply from 1 July 2015 to applications to vary marketing—submitted, for example, to seek authorisation for new indications of already approved drugs. At some point in the future, after further debate on the ethical and technical challenges, the agency intends to also provide access to the anonymised individual patient data from its …
Time since childbirth and prognosis in primary breast cancer: population based study
Authors: N. Kroman, J. Wohlfahrt, K. W. Andersen, H. T Mouridsen, T. Westergaard, M. Melbye
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To investigate whether time since birth of last child was of prognostic importance in women with primary breast cancer. <b>Design:</b> Retrospective cohort study based on a population based database of breast cancer diagnoses with detailed information on tumour characteristics, treatment regimens, reproductive factors, and vital status. <b>Setting:</b> Denmark. <b>Subjects:</b> 5652 women with primary breast cancer aged 45 years or less at the time of diagnosis. <b>Main outcome measures:</b> 5 and 10 year survival; relative risk of dying. <b>Results:</b> Women diagnosed in the first 2 years after last childbirth had a crude 5 year survival of 58.7% and 10 year survival of 46.1% compared with 78.4% and 66.0% for women whose last childbirth was more than 2 years before their diagnosis. After adjustment for age, reproductive factors, and stage of disease (tumour size, axillary nodal status, and histological grading), a diagnosis sooner than 2 years since last childbirth was significantly associated with a poor survival (relative risk 1.58, 95% confidence interval 1.24 to 2.02) compared with women who gave birth more than 5 years previously. Further analyses showed that the effect was not modified by age at diagnosis, tumour size, and nodal status. <b>Conclusion:</b> A diagnosis of breast cancer less than 2 years after having given birth is associated with a particularly poor survival irrespective of the stage of disease at debut. Therefore, a recent pregnancy should be regarded as a negative prognostic factor and should be considered in counselling these patients and in the decisions regarding adjuvant treatment. <h3>Key messages</h3> A childbirth close to subsequent diagnosis of breast cancer has a negative effect on the woman9s cancer prognosis The negative effect of recent childbirth is not affected by age at diagnosis, nodal status, and tumour size The negative effect is found both in patients who receive adjuvant treatment and those who do not Childbirth history should be taken into account when counselling young women with breast cancer
(SWR x SJL)F1 mice: a new model of lupus-like disease.
Authors: S Vidal, C Gelpí, J L Rodríguez-Sánchez
Journal: The Journal of Experimental Medicine (1994)

During the study of autoimmune models we found that (SWR x SJL)F1 mice (both parental strains with the V beta a phenotype) spontaneously produced immunoglobulin G (IgG) antibodies directed against Sm/U1 small nuclear ribonucleoproteins (snRNPs). In some of these females, the presence of these autoantibodies was found as early as 10 wk of age. Their frequency increased with age i.e., 70% at 40 wk. At that time, only 10% of males developed anti-Sm/U1snRNP antibodies. Anti-Sm/U1snRNP antibodies from positive mice generally recognized the peptides BB', D, 70 kD, and A from RNPs. These polypeptides are known to bear the autoantigenic epitopes that are recognized by human sera containing anti-Sm and anti-U1snRNP antibodies. Reactivity of IgG antibodies with the octapeptide sequence PPPGMRPP was also found in 30% of anti-Sm/U1snRNP positive (SWR x SJL)F1 mice that precipitated BB' peptides. This octapeptide has been described as the most immunoreactive linear epitope in systemic lupus erythematosus (SLE) patients with anti-Sm and anti-U1snRNP antibodies. Approximately 30% of anti-Sn/U1snRNP positive females, later produced anti-dsDNA antibodies. This fact was accompanied by the development of proteinuria due to glomerulonephritis mediated by immunocomplexes. In addition to the specific autoimmune response, (SWR x SJL)F1 females also showed other immunologic abnormalities such as hypergammaglobulinemia, and an approximately twofold increase in spleen cell number compared with control mice. These results indicate that (SWR x SJL)F1 females develop clinical and serological abnormalities similar to those observed in human SLE and constitute a novel model for the study of the genetic mechanisms that result in autoimmunity.
Tongue Necrosis Attributed to Ergotamine in Temporal Arteritis
Authors: Jonathan R. Wolpaw
Journal: JAMA (1973)

On two occasions, a woman with temporal arteritis developed tongue cyanosis and numbness shortly after the administration of ergotamine tartrate. Partial necrosis of the tongue resulted. Presumably, the lingual artery compromise, frequently present in temporal arteritis, was made symptomatic by the vasoconstrictive action of ergotamine tartrate.
Will the government's mass media campaign on drugs work?
Authors: A Hansen
Journal: BMJ (1985)

Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic porcine enteropathogenic coronavirus causing severe enteritis and lethal watery diarrhea in piglets. PEDV infection suppresses the synthesis of type I IFN, and multiple viral proteins of PEDV have been shown to target the adaptors of innate immune pathways to inhibit type I IFN production. In this study, we identified PEDV membrane (M) protein as a new antagonist of type I IFN production in both human embryonic kidney HEK293T cells and porcine kidney PK-15 cells and determined the antagonistic mechanism used by M protein to target IFN regulatory factor 7 (IRF7), an important regulator of type I IFN production. IRF7 is phosphorylated and activated by TBK1 and IKKε in response to viral infection. We found that PEDV M protein interacted with the inhibitory domain of IRF7 and significantly suppressed TBK1/IKKε-induced IRF7 phosphorylation and dimerization of IRF7, leading to the decreased expression of type I IFN, although it did not affect the interaction between TBK1/IKKε and IRF7. As expected, overexpression of M protein significantly increased PEDV replication in porcine cells. The M proteins of both epidemic PEDV strains and vaccine strain showed similar antagonistic effect on type I IFN production, and the 1-55 region of M protein was essential for disruption of IRF7 function by interacting with IRF7. Taken together, our data identified a new, to our knowledge, IFN antagonist of PEDV, as well as a novel, to our knowledge, antagonistic mechanism evolved by PEDV to inhibit type I IFN production.
Who Will Benefit From Griseofulvin?
Authors: Frederick A. J. Kingery
Journal: JAMA (1964)

GRISEOFULVIN is an antibiotic which has a fungistatic effect against most of the dermatophytes. It can therefore quite logically be expected to be of value in the management of certain superficial fungal infections. By the same token it is, of course, worthless in those cutaneous diseases of other causes which morphologically resemble common mycotic infections. Since griseofulvin therapy often requires considerable time and expense, it is important to establish an etiological diagnosis at the outset. The following three situations demonstrate this point. A bilateral eczematous eruption involving distal portions of the feet (Fig 1) had its sudden symmetrical onset one month ago. Local treatment with various fungicidal agents merely aggravated the problem. Patch tests to components in the patient's shoes gave a strong delayed eczematous reaction ( 48 hours ) to a sample of the thermoplastic rubber box toe. Complete resolution occurred when a shoe with a plastic toe box was substituted.
Anaphylactic responses to histamine in mice utilize both histamine receptors 1 and 2
Authors: J. B. Wechsler, H. A. Schroeder, A. J. Byrne, K. B. Chien, P. J. Bryce
Journal: Allergy (2013)

Anaphylaxis is a severe, potentially life-threatening reaction that can occur in response to common triggers, including food allergens (e.g., peanut), insect stings, and several medications. Activation of mast cells and basophils to release preformed mediators, such as histamine, is thought to be an important process that underlies reactions. Histamine can exert effects through four different receptors, termed H1R-H4R. Despite clinical use of both H1R and H2R blockers in the therapy for acute allergic reactions, there is little mechanistic evidence to support the necessity for blocking H2R, a receptor best characterized for its role in stomach acid production.Here, we sought to define the necessity for histamine receptors in the pathology of anaphylaxis using H1R and H2R knockout (KO) mice, as well as a H1R/H2R double KO strain.In response to IgE-mediated systemic anaphylaxis, the symptoms and decreases in core body temperature observed in wild-type mice were reduced but not ablated in either H1R or H2R KO. In contrast, H1R/H2R KO were significantly protected and were indistinguishable from histamine-deficient mice. Intravenous injection of histamine was sufficient to elicit these responses, and similar to IgE-mediated anaphylaxis, loss of both H1R and H2R was necessary for complete protection.Our data demonstrate definitively that both H1R and H2R participate in the immediate systemic responses during histamine-associated pathophysiology and mechanistically support the utility of H2R-blocking therapeutics in alleviating symptoms of anaphylaxis.
Effect of BN 52021, a platelet activating factor antagonist, on experimental murine contact dermatitis
Authors: M. CSATO, B.M. CZARNETZKI
Journal: British Journal of Dermatology (1988)

A specific platelet activating factor (PAF) receptor antagonist, BN 52021, was tested for its efficacy in modulating DNFB‐induced allergic and croton oil‐induced irritant contact dermatitis in mouse ears. Oral treatment of the animals in the elicitation phase of the dermatitis caused a significant suppression of DNFB‐induced ear swelling. The compound was less active in croton oil‐induced irritant dermatitis and ineffective when given during the sensitization phase of allergic dermatitis. The results provide indirect evidence for the involvement of PAF in the effector phase of murine contact dermatitis of the allergic type and also the irritant type to a lesser extent.
Extraction of a Key from the Trachea.
Authors: M. G. Sloan
Journal: JAMA (1890)

<h3>To the Editor:</h3> —On the evening of February 14, 1890, Carl Blohm, aged 2 years, was brought to my office by his father, who stated that the boy had "swallowed" a key a few moments before. The patient was voiceless, dyspnœa was constant and alarming, and there was a frequent croupy cough. There was great retraction of the soft parts about the clavicles and in the inframammary regions in inspiration. It was very evident that the foreign body was somewhere in the air passages, and it seemed to me probable that it had not passed much below the larynx, as I could on no other theory account for the complete aphonia. However, neither with the finger nor with a pair of laryngeal forceps was I able to reach it through the mouth. It was plain that relief, to be of avail, must be speedy. Accordingly, after ineffectually trying a vigorous
Slouching Toward Policy: Lazy Bioethics and the Perils of Science Fiction
Authors: Ruth Levy Guyer, Jonathan D. Moreno
Journal: The American Journal of Bioethics (2004)

Too much contemporary bioethical discourse is weak on science, lazily citing and adopting science fiction scenarios rather than science facts in the framing of analyses and policies. We challenge bioethicists to take more seriously the role of providing informed insight into and oversight over contemporary science and its implications and applications. Bioethicists must work harder to understand the fast-changing truths and limits of basic science, and they must incorporate only appropriate and authentic science into their discourse, just as they did in the past when addressing the quandaries of clinical medicine. The field of bioethics is not so old and entrenched that its future is assured. Bioethicists must make themselves useful to society in order to deserve and retain the public's trust. They can best do this by ensuring that decision making and public policy are grounded in facts, not fictions and fantasies.
Haemangioma: clinical course, complications and management
Authors: M. Luu, I.J. Frieden
Journal: British Journal of Dermatology (2013)

Despite their high incidence, most infantile haemangiomas (IH) do not require treatment as they regress spontaneously and most do not leave significant sequelae. For the subset of haemangiomas that require treatment, indications for intervention can be divided into three main categories: ulceration, disfigurement and impairment of function or vital structures. In addition, certain IH have a risk of associated structural anomalies. Given the wide heterogeneity of haemangiomas, deciding which haemangiomas need intervention and when to intervene requires a detailed knowledge of natural history and clinical indicators of increased risk.