tbuckley/cabot-search huggingface dataset:
A Tissue-specific NF- B inhibitor ameliorates inflammatory joint diseases
Authors: B. Sehnert, H. Burkhardt, F. Nimmerjahn, S. Pohle, J. Wessels, D. Vestweber, J. Zwerina, G. Schett, S. Dubel, R. Voll
Journal: Annals of the Rheumatic Diseases (2010)

The nuclear transcription factorκB (NFκB) is a potential molecular target for anti-inflammatory therapy. The NFκB pathway is crucial to the transcriptional activation of multiple mediators involved in the initiation and maintenance of inflammatory processes such as arthritis. The present study was undertaken to investigate the potency of a novel class of NFκB inhibitors that interfere with the NFκB signalling pathway selectively in endothelial cells, a cell type that plays an important role in the extravasation of leucocytes …
REACTIONS OF RABBITS TO INTRACUTANEOUS INJECTIONS OF PNEUMOCOCCI AND THEIR PRODUCTS
Authors: Louis A. Julianelle
Journal: The Journal of Experimental Medicine (1930)

1. Following repeated intracutaneous injections of heat-killed pneumococci rabbits acquire an increased skin reactivity. 2. The increased skin reactivity reaches a maximum after 4 to 6 injections have been made, after which it becomes greatly diminished. 3. The relationship of increased skin reactivity to active resistance to infection by Pneumococcus, and to the presence of species-specific antibodies in the blood, is still obscure. 4. The increased skin reactivity is not transferable by serum from a highly reactive to a normal rabbit. 5. After regression of the reaction to the first injection of Pneumococcus into the skin, there frequently follows a recrudescence, or exacerbation, of the reaction. 6. The increased skin reactivity and secondary reactions are incited alike by all types and all forms of Pneumococcus.
Experimentation or observation? Of the self alone or the natural world?
Authors: Emanuel A. Schegloff
Journal: Behavioral and Brain Sciences (2004)

One important lesson of Roberts' target article may be potentially obscured for some by the title's reference to "self-experimentation." At the core of this work, the key investigative resource is sustained and systematic observation, not experimentation, and it is deployed in a fashion not necessarily restricted to self-examination. There is an important reminder here of a strategically important, but neglected, relationship between observation and experiment.
Immediate hypersensitivity to aztreonam and imipenem.
Authors: P Hantson, B de Coninck, J L Horn, P Mahieu
Journal: BMJ (1991)

SIR, -Dr Christopher Law asks how many reports are requested of doctors and why arrangements exist for such reports to be paid for outside NHS remuneration.'The answer to the first question is, "All to many!" General practitioners in particular receive a myriad of requests for reports, some of doubtful necessity.In regard to the second question, there is no doubt that the requirement to pay for these reports on an item of service basis is responsible for preventing even more requests for reports.Moreover, in these days of cross charging between all government departments it would be invidious for general practitioners, who are independent con- tractors, or indeed hospital doctors, who are salaried to the NHS, to be asked to subsidise a department outside the NHS.With regard to completion of the report for patients claiming attendance allowance under the new "special rules," the fee agreed with the Department of Social Security takes into account those patients whose records take much longer to examine before the form can be completed.
Screening for colonic cancer in patients with Barrett's oesophagus.
Authors: D. A. Robertson, R. C. Ayres, C. L. Smith
Journal: BMJ (1989)

addition to written reports is required to gain a comprehensive view of performance.In the United States this type of monitoring by a physician is recommended for all cases of cardiac arrest treated by emergency medical technicians using advanced skills.'No such recommendations exist in the United King- dom.Monitoring of electrocardiograms and cassette tapes is time consuming and requires additional equip- ment.' Lack of resources or medical support, in addition to the lack of official directives, may result in ambulance services failing to monitor standards, and the full potential of advanced trained ambulance staff will not be achieved.We thank Marks and Spencer for funding this research, Miss S Smith for preparing the manuscript
"Imferon" and Cancer
Authors: J. J. R. Duthie, R. H. Girdwood, D. Hubble, A. G. Macgregor, E. J. Wayne, A. Wilson, G. M. Wilson
Journal: BMJ (1960)

<h3>ABSTRACT</h3> Evaluating how wildlife conservation laws are implemented is critical for safeguarding biodiversity. Two agencies, the U.S. Fish and Wildlife Service and National Marine Fisheries Service (FWS and NMFS; Services collectively), are responsible for implementing the U.S. Endangered Species Act (ESA), which requires federal protection for threatened and endangered species. FWS and NMFS’ comparable role for terrestrial and marine taxa, respectively, provides the opportunity to examine how implementation of the same law varies between agencies. We analyzed how the Services implement a core component of the ESA, section 7 consultations, by objectively assessing the contents of &gt;120 consultations on sea turtle species against the requirements in the Services’ consultation handbook, supplemented with in-person observations from Service biologists. Our results showed that NMFS consultations were 1.40 times as likely to have higher completeness scores than FWS consultations given the standard in the handbook. Consultations tiered from an FWS programmatic consultation inherited higher quality scores of generally more thorough programmatic consultations, indicating that programmatic consultations could increase the quality of consultations while improving efficiency. Both agencies commonly neglected to account for the effects of previous consultations and the potential for compounded effects on species. From these results, we recommend actions that can improve quality of consultation, including the use of a single database to track and integrate previously authorized harm in new analyses and the careful but more widespread use of programmatic consultations. Our study reveals several critical shortfalls in the current process of conducting ESA section 7 consultations that the Services could address to better safeguard North America’s most imperiled species.
An Embryologically Derived Classification of Ovarian Tumors
Authors: Milton L. Bassis
Journal: JAMA (1960)

The following classification of ovarian tumors has an embryologic foundation, with the cellular background of the tumors determined in embryonic life and their differentiation into the various types determined by the genetic potentialities of their cells of origin. This results in attempts by the tumor to recapitulate in morphology the various stages in the development of the urogenital ridge, namely, the mullerian apparatus, germ cells, primitive gonads, and adrenals. <h3>Embryology1-2</h3> The genital system first appears in the fifth to sixth week of embryonic life as an undifferentiated structure, with the occurrence of a localized thickening, the urogenital ridge, on each side of the dorsal mesentery bulging ventrally into the coelom. This common fold subdivides longitudinally into a more lateral mesonephric ridge and a medial genital ridge. Both sexes develop a pair of female ducts, the mullerian ducts, as the result of a groove developing in the thickening epithelium of
Physiologically based pharmacokinetics and cancer risk assessment.
Authors: M E Andersen, K Krishnan
Journal: Environmental Health Perspectives (1994)

Physiologically based pharmacokinetic (PBPK) modeling involves mathematically describing the complex interplay of the critical physicochemical and biological determinants involved in the disposition of chemicals. In this approach, the body is divided into a number of biologically relevant tissue compartments, arranged in an anatomically accurate manner, and defined with appropriate physiological characteristics. The extrapolation of pharmacokinetic behavior of chemicals from high dose to low dose for various exposure routes and species is possible with this approach because these models are developed by integrating quantitative information on the critical determinants of chemical disposition under a biological modeling framework. The principal application of PBPK models is in the prediction of tissue dosimetry of toxic moiety (e.g., parent chemical, reactive metabolite, macromolecular adduct) of a chemical. Such an application has been demonstrated with dichloromethane, a liver and lung carcinogen in the B6C3F1 mouse. The PBPK model-based risk assessment approach estimated a cancer risk to people of 3.7 x 10(-8) for a lifetime inhalation exposure of 1 micrograms/m3, which is lower by more than two orders of magnitude than that calculated by the U.S. Environmental Protection Agency using the linearized multistage model (for low-dose extrapolation) and body surface correction factor (for interspecies scaling). The capability of predicting the target tissue exposure to toxic moiety in people with PBPK models should help reduce the uncertainty associated with the extrapolation procedures adopted in conventional dose-response assessment.
PRIMARY SERUM TOXICITY AS DEMONSTRATED BY THE CHICKEN EMBRYO
Authors: Ernst Witebsky, Erwin Neter
Journal: The Journal of Experimental Medicine (1935)

1. The 3 day old chicken embryo removed from its shell is a suitable test object for the demonstration of primary serum toxicity. Addition of normal rabbit type sera as well as Forssman antiserum causes the vascular network to contract and the embryo sinks in the yolk and dies. 2. Only sera of animals of the so called rabbit type produce this phenomenon. Sera of the guinea pig type are ineffective. 3. Heating to 51 degrees C. destroys the complement content of normal human serum as also its effectiveness to produce the vascular phenomenon. 4. Up to the present it has not been possible to reactivate heat-inactivated normal serum by the addition of complement, while inactivated Forssman antiserum can be easily reactivated. 5. The vascular phenomenon of the chicken embryo is produced not only by the addition of a mixture of Forssman antiserum and complement but also by separate addition of both components. 6. Guinea pig type sera, containing dissolved Forssman antigen, are not only ineffective but actually exert an inhibitory influence on effective rabbit type sera as well as on Forssman antiserum.
PML in a Patient without Severe Lymphocytopenia Receiving Dimethyl Fumarate
Authors: Dennis J Nieuwkamp, Jean-Luc Murk, Bob W van Oosten, Charlotte H P Cremers, Joep Killestein, Marco C Viveen, Wim Van Hecke, Daphne W Frijlink, Mike P Wattjes
Journal: New England Journal of Medicine (2015)

Progressive multifocal leukoencephalopathy developed in a 64-year-old woman who was treated with compounded dimethyl fumarate for psoriasis. Lymphocytopenia in this patient was not as severe as in other patients with PML receiving fumaric acid esters.
The relationship between pericardial pressure and right atrial pressure: an intraoperative study.
Authors: J V Tyberg, G C Taichman, E R Smith, N W Douglas, O A Smiseth, W J Keon
Journal: Circulation (1986)

The objective of this study was to determine the constraining effect of the normal human pericardium. Accordingly, immediately after thoracotomy in nine patients undergoing elective cardiac surgery, we measured mean pericardial surface pressure over the lateral free wall of the left ventricle with a flat balloon as well as mean right atrial pressure while incrementally infusing up to 2.1 liters of Ringer's solution to increase right atrial pressure. In each case, the slope of the relationship between right atrial (range -4 to 20 mm Hg, overall) and pericardial pressures was near unity (1.16 +/- 0.20 mean +/- SD) and the intercept was approximately zero (0.71 +/- 2.48 mm Hg). Correlation coefficients ranged from .86 to .97. These observations suggest that right atrial pressure can be used as an estimate of pericardial surface pressure. If this is the case, true left ventricular preload (i.e., effective distending pressure or transmural diastolic pressure) might be estimated from the difference between left ventricular filling pressure and right atrial pressure, both conveniently measurable clinically by means of a triple-lumen, flow-directed catheter.
Abnormal redox status of membrane-protein thiols in sickle erythrocytes.
Authors: B H Rank, J Carlsson, R P Hebbel
Journal: Journal of Clinical Investigation (1985)

Although sickle erythrocytes (RBC) undergo excessive autooxidation, investigators have not found evidence for abnormal oxidation of protein thiols in sickle RBC membranes (e.g., protein aggregates linked by intermolecular disulfide bonds). However, the conventional techniques heretofore used cannot detect more subtle changes in thiol status such as abnormal intramolecular disulfide bonds. We examined RBC membranes using thiol-disulfide exchange chromatography which partitions sodium dodecyl sulfate-solubilized proteins on the basis of reactive thiols, yielding gel-bound (reduced-thiol) and filtrate (oxidized/blocked-thiol) fractions. Membranes from normal RBC partition so that only 13.6 +/- 1.4% of all membrane protein is found in the filtrate fraction. An abnormally increased amount of membrane protein from sickle RBC (21.5 +/- 4.3%) partitions into the filtrate fraction (P less than 0.001). Since sickle RBC do not have high molecular weight aggregates of membrane protein, this indicates abnormal intramolecular thiol oxidation in sickle RBC membranes. Treatment of normal RBC with thiol blockers and oxidants simulates this shift of membrane protein into the filtrate fraction. Analysis using polyacrylamide gel electrophoresis reveals that the filtrate fraction derived from normal RBC consists mostly of band 7 and glycophorins, with only trace amounts of other membrane proteins. Superimposed upon this normal background, sickle RBC filtrates are enriched with all proteins (including cytoskeletal protein bands 1, 2, 2.1, and 4.1), suggesting a generalized oxidative perturbation of sickle RBC membranes. These observations support the concept that excessive RBC autooxidation may play a role in sickle disease pathophysiology, and they perhaps help explain the development of those membrane abnormalities that may reflect cytoskeletal dysfunction in sickle erythrocytes.
Advances in Uterine Leiomyoma Research: The Progesterone Hypothesis
Authors: Mitchell S. Rein
Journal: Environmental Health Perspectives (2000)

Uterine leiomyomas are monoclonal tumors. However, the factors involved in their initiation and growth remain poorly understood. The neoplastic transformation of myometrium to leiomyoma likely involves somatic mutations of normal myometrium and the complex interactions of sex steroids and local growth factors. Traditionally, estrogen has been considered the major promoter of myoma growth. The purpose of this review is to highlight the biochemical, histologic, and clinical evidence that supports an equally important role for progesterone in the growth of uterine myomas. Biochemical studies suggest that progesterone, progestins, and the progesterone receptor modulate myoma mitotic activity. A hypothesis to explain the pathogenesis of myomas is presented.
District cancer physicians: integration or fragmentation?
Authors: L J Donaldson
Journal: BMJ (1987)

highly reminiscent of those reported in some schizophrenics.Hitherto it has been difficult to acount for the excess of births in winter or the sex difference in age of onset in schizophrenia.Similarly, arguments over the importance of soft neurological signs, cognitive impairment, and abnor- malities oflaterality have not been resolved.But a model that regards early neurodevelopmental deviance as one of several risk factors does provide a unifying explanation for what until now have been regarded as curious epiphenomena of schizophrenia.
Relationship of gold and penicillamine therapy to diffuse interstitial lung disease.
Authors: D L Scott, G V Bradby, T J Aitman, G C Zaphiropoulos, C F Hawkins
Journal: Annals of the Rheumatic Diseases (1981)

Seven cases of diffuse interstitial lung disease (DILD) are reported with an unequivocal temporal relationship between the development of the lung disease and treatment with gold (6 cases) and penicillamine (1 case). They were characterised clinically by the sudden onset of dyspnoea and crepitations and radiologically by diffuse bilateral pulmonary shadowing. Most showed evidence of hypersensitivity such as eosinophilia, a raised serum IgE level in response to gold, proteinuria, thrombocytopenia, or an immediate postinjection reaction. DILD is a serious complication of treatment with gold and penicillamine that is commoner than generally realised.
Mathematics is bad for you: population risk reduction medicalises us all
Authors: J. L. Fanu
Journal: BMJ (2012)

3,3′-Diindolylmethane (DIM), a natural autolytic product in plants of the <i>Brassica</i> genus, including broccoli, cauliflower, and Brussels sprouts, exhibits promising cancer protective activities, especially against mammary neoplasia in animal models. We observed previously that DIM induced a G<sub>1</sub> cell-cycle arrest and strong induction of cell-cycle inhibitor p21 expression and promoter activity in both estrogen-responsive and -independent breast cancer cell lines. We showed recently that DIM up-regulates the expression of interferon γ (IFNγ) in human MCF-7 breast cancer cells. This novel effect may contribute to the anticancer effects of DIM because IFNγ plays an important role in preventing the development of primary and transplanted tumors. In this study, we observed that DIM activated the IFNγ signaling pathway in human breast cancer cells. DIM activated the expression of the IFNγ receptor (IFNGR1) and IFNγ-responsive genes p56- and p69-oligoadenylate synthase (OAS). In cotreatments with IFNγ, DIM produced an additive activation of endogenous p69-OAS and of an OAS-Luc reporter and a synergistic activation of a GAS-Luc reporter. DIM synergistically augmented the IFNγ induced phosphorylation of signal transducer and activator of transcription factor 1, further evidence of DIM activation of the IFNγ pathway. DIM and IFNγ produced an additive inhibition of cell proliferation and a synergistic increase in levels of major histocompatibility complex class-1 (MHC-1) expression, accompanied by increased levels of mRNAs of MHC-1-associated proteins and transporters. These results reveal novel immune activating and potentiating activities of DIM in human tumor cells that may contribute to the established effectiveness of this dietary indole against various tumors types.
Clindamycin-induced esophageal ulceration
Authors: G. Wagenvoort, W. van Mook, A. Bodelier
Journal: Endoscopy (2011)

A 24-year-old man, with no prior medical history, presented with acute-onset mid-chest pain, aggravated by swallowing. The pain had begun 6 days previously when the man was lying down. The patient had taken the last dose of three 300-mg clindamycin tablets for mild folliculitis, 1 hour before onset of the symptoms. Self-prescribed pantoprazole – 20 mg for 3 days – had provided no relief.
Growth factors in reproduction
Authors: Linda C. Giudice, Walid Saleh
Journal: Trends in Endocrinology and Metabolism (1995)

The changes that occur in the female reproductive tract during the menstrual cycle and in early pregnancy, in preparation for embryo implantation and subsequent placental and fetal development, have long attracted the interest of reproductive biologists. The early embryo expresses growth factors and growth factor receptors that are, in general, temporally expressed. In addition, the oviduct and uterine endometrium also synthesize growth factors and cytokines, and the developing embryo finds itself in a growth-factor-rich milieu during early development. The autocrine, juxtracrine, and paracrine actions of these factors in the development of the early embryo and of the maternal reproductive tract are just beginning to be appreciated, as are their potential roles in cellular proliferation and cell-cell communication within the developing embryo, in the reproductive tract, and at the maternal-trophoblast interface. When detailed mechanisms underlying these interactions are fully understood, it is anticipated that therapies will be rationally designed to treat reproductive disorders associated with abnormal embryonic development and poor placentation.
Clindamycin-Associated Colitis With Toxic Megacolon
Authors: Morris Axelrod
Journal: JAMA (1975)

<h3>To the Editor.—</h3> Lincomycin and clindamycin have been reported as causing a spectrum of diarrheal diseases ranging from mild nonspecific colitis to severe pseudomembranous colitis, which may be lethal.<sup>1-6</sup>We wish to report a patient presently in our care for clindamycin-induced pseudomembranous colitis complicated by toxic megacolon. <h3>Report of a Case.—</h3> A 30-year-old, previously healthy man was admitted on Jan 7, 1975, with a two-week history of diarrhea, at times bloody. Prior to admission, he had been treated in the emergency rooms of two hospitals and given a mixture of kaolin, pectin, atropine, scopolamine, and hyoscyamine (Donnagel) and a mixture of atropine sulfate and diphenoxylate hydrochloride (Lomotil), without relief. Because of worsening diarrhea, upper abdominal pain, and dehydration, he was admitted to our hospital with the diagnosis of enterocolitis. On admission, he was acutely ill and dehydrated. Pulse rate was 110 beats per minute; temperature was 37.8 C (100
European Commission's new president puts public health on the agenda
Authors: R. Watson
Journal: BMJ (1999)

The incoming president of the European Commission, Romano Prodi, is determined to move responsibility for public health higher up the European Union's political agenda. He is also considering the creation of a food safety agency along the lines of the US Food and Drug Administration.

As Mr Prodi and his colleagues prepare to begin their five year term of office in September, he is restructuring the commission's internal bureaucracy to create a major new department. This will be …
Developing new hepatitis B immunisation strategies.
Authors: A J Zuckerman
Journal: Gut (1996)

The four main approaches to immunisation against hepatitis B are: vaccination of high risk babies; universal adolescent immunisation; universal infant immunisation; and vaccination of everybody. Universal antenatal screening would permit identification of carrier mothers and immunisation of their babies. Vaccination of adolescents would provide protection close to the time when risk of exposure increases, and could be delivered as part of a wider package on health education. Universal vaccination of infants is the best option because it is known that vaccines can be delivered to babies and it is more acceptable to parents. Development of a combined hepatitis B-diphtheria-pertussis-tetanus vaccine would be beneficial. The identification of hepatitis B antibody escape mutants is of concern because of the implications for vaccine efficacy. Altered or absent expression of the hepatitis B virus (HBV) antigenic group determinant a may allow infection even in subjects who have responded previously to vaccination.
Death by tsunami and poverty
Authors: Kamran Abbasi
Journal: BMJ (2005)

Fishermen in the Indian Ocean were unaware of the wave that swept past them and devastated their homes and families. How many of us are unaware that over a million people died in the 1970s after a cyclone struck Bangladesh and an earthquake shook China? What, then, makes this tsunami disaster so potent—beyond unprecedented television and newspaper coverage—that the United Nations will have launched a flash appeal by the time you read this week's BMJ ?

A wave that killed on two continents is a stark reminder that the many divisions within and between nations are insignificant when …