tbuckley/cabot-search huggingface dataset:
Hotspots of immune response to tumours can predict breast cancer progression, study shows
Authors: S. Mayor
Journal: BMJ (2015)

A test that analyses hotspots of the immune response to tumour tissue offers a new approach to predicting survival and the response to treatment, a study of women with breast cancer has found.

Researchers analysed tumour samples from 245 women with oestrogen receptor negative breast cancer by using statistical software previously used for measuring spatial interactions in ecological and …
Morris Fishbein, MD-1889-1976, editor of JAMA-1924-1950
Authors: W. R. Barclay
Journal: JAMA (1976)

On September 27, 1976, the medical profession lost one of its most distinguished and important members with the death of Morris Fishbein. His place in medicine was not secured by providing medical care nor by laboring in the research laboratory. His contributions were those of editor, author, lecturer, teacher, critic, and philosopher, and in these roles he was unsurpassed.  Endowed with a prodigious memory, a brilliant intellect, and tireless energy, he became medicine's most colorful, well-known, and influential person.  Shortly after he graduated from Rush Medical College in 1913, Doctor Fishbein became assistant to Dr George H. Simmons, editor of The Journal of the American Medical Association . In 1924 he succeeded to the editorship of this journal, a position he held until 1950.The Journal, first published in 1883, has had 12 editors to this date, and of these, Morris Fishbein held the editorship the longest. Counting his term as
Diseases of Food Hypersensitivity
Authors: Dean D. Metcalfe
Journal: New England Journal of Medicine (1989)

IN 1912, Schloss reported that a child who had had adverse reactions after eating certain foods had itching and redness at the site of scarification of the skin onto which drops of extracts from these foods had been applied.1 At about the same time, Talbot observed that children with asthma and eczema due to "egg poisoning" also had skin reactions to an extract of egg.2 Later, in 1921, Prausnitz and Küstner3 demonstrated that the factor responsible for sensitivity to fish was present in the serum of a fish-sensitive subject. This observation was the basis of the P-K test, now known . . .
Drugs Five Years Later: Bleomycin
Authors: JOHN M. BENNETT
Journal: Annals of Internal Medicine (1979)

Bleomycin was approved by the Food and Drug Administration in 1975 for therapy against squamous cell carcinomas, testicular cancers, and malignant lymphomas. An extensive bibliography on this drug indicates that there is little evidence of activity against other malignancies. Although initially used exclusively as a single agent, bleomycin has been considered recently for use in combination chemotherapy. Because of associated toxicity involving the lung and mucous membranes, bleomycin should be used cautiously by physicians, particularly in noninvestigational settings.
Altered expression of the hemidesmosome-anchoring filament complex proteins in basal cell carcinoma: possible role in the origin of peritumoral lacunae
Authors: Ph. BAHADORAN, Ch. PERRIN, D. ABERDAM, A. SPADAFORA-PISANI, G. MENEGUZZI, J-P. ORTONNE
Journal: British Journal of Dermatology (1997)

Basal cell carcinoma (BCC) is a frequent skin cancer with low metastatic potential. Expression of the anchoring filament proteins, native laminin-5 and its individual alpha 3, beta 3 and gamma 2 chains, uncein. and linear IgA antigen was examined by immunostaining in 17 BCC with different histological subtypes. Immunoreactivity of the hemidesmosomal proteins, integrin alpha 6 beta 4, 230-kDa bullous pemphigoid antigen (BP-230 Ag) and plectin/HD-1, and that of dermal-epidermal junction (DEJ) components, integrin alpha 2 beta 1, laminin-1, collagen IV, and collagen VII was also analysed. Around tumour nests, the labelling of laminin-5 was absent or markedly reduced in 12 BCC (comprising eight solid BCC, three adenoid BCC and one keratotic BCC) and strong in five BCC (comprising three adenoid BCC, one keratotic BCC and one adenoid and keratotic BCC). Intriguingly, in tumour cells of 12 BCC including laminin-5 negative tumours, a cytoplasmic reactivity of the laminin gamma 2 chain was detected, but not that of the alpha 3 and beta 3 chains. In the basement membrane of the epidermis overlying tumour nests, the labelling of laminin-5 was always strong. Uncein, linear IgA disease antigen, and integrin alpha 6 beta 4 were absent in solid BCC and weakly expressed in adenoid or keratotic BCC. For plectin/HD-1 and BP-230 Ag, a cytoplasmic reactivity was detected in the majority of the tumour cells. The labelling of integrin alpha 2 beta 1, laminin-1, collagen IV and collagen VII indicated no alteration in the synthesis of these proteins. In peritumoral lacunae, immunoreactivity of hemidesmosome and anchoring filament proteins was absent, except for plectin/HD-1 on the tumour side and sometimes for laminin-5 on the stromal side, while laminin-1, collagen IV and collagen VII were detected on the stromal side. These findings suggest that the components of the hemidesmosome-anchoring filament complex are not synthetized or assembled properly in BCC, and that the alteration of these adhesion structures may be the cause of peritumoral lacunae.
Outbreak of Dysentery Due to Contact with a Pet Monkey
Authors: D. T. Robinson, E. C. Armstrong, K. P. Carpenter
Journal: BMJ (1965)

Herpes Simplex-7uel-7ensen and MacCallMm BRITJSH 903 relapsed after an interval, but none to date have had a lesion in the same site, although they stated that this had always occurred previously.It remains to be seen to what extent the treatment is curative when it has been applied.Failure in method (inadequate cover of the whole affected area) may explain why some patients derived little benefit from the treat- ment, or the virus may have been I.D.U.-resistant.All strains isolated are being examined for this property.All lesions occurred on the face round the mouth, on the lips, and in one instance on the nose.The unusual form of treatment presented no major practical problems in the group investigated.The patients feel a sharp impact, and may ooze a little blood from the entry wound for a minute or two.On the other hand many expressed delight with the (as it turned out) real shortening of the attack, and commented on the rapidity with which the unpleasant itching and tingling went, often within an hour.This seems to be a real advantage in the group treated with I.D.U. (10of 12 in the active, 3 of 11 in the placebo group).We have since used the spray gun in the treatment of herpetic paronychia, and have found that the duration of the lesions was apparently shortened, that the virus disappeared or became very scanty after treat- ment, and that the patient experienced relief from the often excruciating pain in this condition. SummayTwenty-three patients with herpes of the face participated in a double-blind controlled trial to test the effect of 5-iodo-2'- deoxyuridine (idoxuridine), 0.1% in aqueous solution.The solution was applied with a modified airgun for intradermal in- jection.In 12 patients receiving the active I.D.U.solution in a single treatment there was an average shortening of the dura- tion of the lesion of 3.32 days (or 37%) compared with the average duration (8.87 days) in 11 receiving saline.A true therapeutic effect of I.D.U. on herpes infections of the skin has been demonstrated.Our thanks are due to Dr. T. A. Turnbull, of Smith Kline and French Laboratories Ltd., for the supply of I.D.U
REPORT OF CASES OF CARBON MONOXIDE POISONING TREATED BY METHYLENE BLUE INJECTION
Authors: A. W. Christopherson
Journal: JAMA (1933)

I wish to report further confirmative evidence of the value of methylene blue (methylthionine chloride U. S. P.) in the treatment of carbon monoxide poisoning. Recently five men were brought to me for emergency treatment following a "mysterious" poisoning. They had been working with a road construction crew and were blasting rock in a tunnel measuring 6 by 10 by 115 feet. The blast was set at the depth of the tunnel and ten minutes later two of the men entered the tunnel to commence work. After a few moments one of them sensed the danger and warned the other to run. The latter collapsed almost immediately and the former ran but collapsed at the mouth of the tunnel, where he was dragged to safety. One man ran into the tunnel and rescued the fallen man, but he also collapsed when safely within reach of others. These three were rushed
Whispering Through the Keyhole
Authors: Brent W. Beasley
Journal: JAMA (1997)

This is a case report, of sorts. One possibly for the record books, yet not to define a new disease or an innovative treatment. I could give you a packaged, neat synopsis of this Woman's presentation and highlight her puzzling neurological findings. But that's not what I see when I remember the event. I see her hand. Joan didn't have a personal physician, so when the emergency staff decided she needed admission, she was assigned to our residency service. The nurse plopped Joan's chart by my elbow as she hurried by and barked, "Room 2!" I completed the admission notes of my previous patient, finished off a Dr Pepper, and rounded the corner to meet my new patient, pulling my lab coat around me to ward off the 65-degree temperature of the hospital. Emergency department nurses and technicians were flitting about the area where "Room 2," enclosed by mere curtains
In search of afferent pathways of a cardiogenic hypertensive chemoreflex.
Authors: M D Thames, U J Johannsen, A L Mark
Journal: Circulation (1987)

Injection of serotonin (5-HT) into the left atrium or ventricle activates a hypertensive chemoreflex. The primary purpose of our study was to determine the afferent pathway(s) that mediates this response. A secondary goal was to localize the receptive sites of this reflex. We measured changes in arterial pressure, reflex vascular responses in skeletal muscle and paw, and changes in renal nerve traffic that occurred after the left atrial or left ventricular injection of 5-HT. Injection of 5-HT (100 to 600 micrograms) into left atrium or ventricle produced large reflex increases in vascular resistance and sympathetic outflow. These responses were not reduced after bilateral cervical vagotomy. In separate experiments, increases in renal nerve traffic with left ventricular injection of 5-HT were assessed before and after cardiac sympathetic deafferentation. Interruption of cardiac sympathetic afferent pathways did not significantly attenuate increases in renal nerve activity with 5-HT. Injection of 5-HT (300 micrograms) into the aortic root produced large increases in arterial pressure but this was not observed after injections into the vertebral or common carotid arteries or descending aorta. Injection of 5-HT (100 micrograms) into the left main coronary artery (perfused via a Gregg cannula from an external reservoir) resulted in a depressor reflex (Bezold-Jarisch). In contrast, injection of 5-HT (200 micrograms) into the left ventricle when the drug was prevented from reaching the left coronary artery produced a large pressor response.(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic Thyrotoxic Myopathy with Involvement of Respiratory and Bulbar Muscles
Authors: D. Gaan
Journal: BMJ (1967)

The gel obtained from the cyst in Case 2 was stored frozen at -20°C.A portion was analysed by the microKjeldahl method and found to contain 0.52 % nitrogen, corresponding to a protein content of approximately 3%.The remainder of the gel was lyophilized and 3 mg. of the dried material was hydrolysed with 1 ml.6N HC1 in an evacuated sealed tube at 1150 C. for 20 hours.Hydrochloric acid was removed from the hydro- lysate in a rotary evaporator and the residue analysed for amino- acids by Piez and Morris's (1960) modification of the method of Spackman, Stein, and Moore (1958).The results are shown in the Table, where they are compared with values for collagen from human tendon (Eastoe, 1955) and elastin from bovine aorta (Gotte, Stem, Elsden, and Partridge, 1963).The absence of hydroxyproline and hydroxylysine from the hydrolysate was confirmed by paper chromatography with the use or butanol/acetic acid/water (4:1:5) and water-saturated phenol as solvents and both ninhydrin and isatin as staining reagents.The paper chromatograms confirmed the presence of substantial amounts of glucosamine.
TWIST1 Is an ERK1/2 Effector That Promotes Invasion and Regulates MMP-1 Expression in Human Melanoma Cells
Authors: Michele B. Weiss, Ethan V. Abel, Melanie M. Mayberry, Kevin J. Basile, Adam C. Berger, Andrew E. Aplin
Journal: Cancer Research (2012)

Abstract Tumor cells often use developmental processes to progress toward advanced disease. The E-box transcription factor TWIST1 is essential to epithelial–mesenchymal transition (EMT) and cell migration in the developing neural crest. In melanoma, which derives from the neural crest cell lineage, enhanced TWIST1 expression has been linked to worse clinical prognosis. However, mechanisms underlying TWIST1 expression and whether aberrant TWIST1 levels promote steps in melanoma progression remain unknown. Here, we report that elevated TWIST1 mRNA/protein expression is dependent on extracellular signal-regulated kinase (ERK)1/2 signaling, which is hyperactive in the majority of melanomas. We show that TWIST1 protein levels are especially high in melanoma cell lines generated from invasive, premetastatic stage tumors. Furthermore, TWIST1 expression is required and sufficient to promote invasion through Matrigel and spheroid outgrowth in three-dimensional dermal-mimetic conditions. Alterations to spheroid outgrowth were not as a result of altered cell death, cell-cycle profile, or paradigm EMT protein changes. Importantly, we identify matrix metalloproteinase-1 (MMP-1) as a novel downstream target of TWIST1. We have determined that TWIST1 acts, in a dose-dependent manner, as a mediator between hyperactive ERK1/2 signaling and regulation of MMP-1 transcription. Together, these studies mechanistically show a previously unrecognized interplay between ERK1/2, TWIST1, and MMP-1 that is likely significant in the progression of melanoma toward metastasis. Cancer Res; 72(24); 6382–92. ©2012 AACR.
Relationship of Incorrect Dosing of Fibrinolytic Therapy and Clinical Outcomes
Authors: Rajendra H. Mehta
Journal: JAMA (2005)

Context Incorrect dosing of alteplase has been associated with worse clinical outcomes in patients.However, patients at high risk of adverse events are more prone to dosing errors, thus confounding this relationship.Objective To determine if the association between incorrect dosing of alteplase and adverse outcomes is related to cause and effect or to confounding.Design, Setting, and Patients Observational analysis in May 2004 of a doubleblind, double-dummy trial of 16 949 patients with ST-segment elevation myocardial infarction who were enrolled in the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) trial and were assigned to either a bolus of tenecteplase (with alteplase placebo bolus plus infusion) or a bolus of alteplase (with tenecteplase placebo plus infusion).Main Outcome Measures Thirty-day mortality, in-hospital stroke, and major bleeding associated with incorrect dosing of active alteplase compared with placebo alteplase. ResultsIncorrect dosing occurred in 4.9% of patients who received active alteplase and in 4.6% of patients who received alteplase placebo.Patients receiving incorrect doses of alteplase or alteplase placebo were more likely to be older, female, black, shorter, have lower body weight and systolic blood pressure, and have a higher Killip class at presentation.Thirty-day mortality was higher in patients who received an overdose (9.8%) or underdose (19.5%) of alteplase compared with those who received a correct dose (5.4%).The same pattern was present in patients who received an alteplase placebo (10.0% for overdose, 23.5% for underdose, and 5.4% for correct dose).Similar patterns were seen for in-hospital intracranial hemorrhage and major bleeding.The higher rates of adverse outcomes with incorrect dosing were largely accounted for by adjusting for baseline characteristics.Conclusions The relationship between incorrect dosing and patient outcome in ASSENT-2 is primarily due to confounding factors rather than incorrect dosing itself.These data highlight the need for caution when ascribing a causal relationship to associations between incorrect dosing and adverse outcomes.
572. Alveolar Epithelial Cell-Specific Plasmid Nuclear Import
Authors: James V. DeGiulio, David A. Dean
Journal: Molecular Therapy (2005)

A major concern regarding naked DNA delivery, both in vivo and in vitro, is the relatively low level of gene expression observed following transfection of non-dividing cells. This low level of gene expression is due in part to the relative inaccessibility of plasmid to the nucleus where the cellular transcriptional machinery resides. Many groups have had success customizing plasmid vectors to facilitate DNA nuclear transport. To enhance nuclear import of plasmids, a specific DNA nuclear targeting sequence (DTS) can be included within the plasmid. These sequences bind a subset of newly synthesized transcription factors in the cytoplasm and the plasmid is transported into the nucleus via nuclear localization signals within the DNA-bound transcription factor proteins. Our lab has shown that by using specific DTSs, which bind cell-specific transcription factors, nuclear import of plasmid DNA and subsequent gene expression can be restricted to specific cell types. The experiments presented here describe our identification of a new cell-specific DTS that functions in a class of cells in the lung epithelium. The lung alveolar epithelium contains two morphologically and functionally distinct cell types known as type I (ATI) and type II (ATII) cells. Because several lung diseases specifically affect ATII cells, this cell type is an attractive target for gene delivery. To identify an ATII-specific DTS, a set of ATII-specific promoter sequences were cloned into plasmids lacking any other DTS and these plasmids were microinjected into the cytoplasm of A549 and MLE-12 cells, both ATII-like cell lines. The localization of plasmid DNA was determined eight hours post-injection using in situ hybridization. Of all the sequences tested, only a fragment of the human surfactant protein C (SP-C) promoter (-318 to +18), when included on a plasmid, mediated nuclear import in A549 and MLE-12 cells. When plasmids containing the SP-C promoter were cytoplasmically microinjected into non-ATII cell types (HeLa, TC7, pulmonary smooth muscle cells, and bronchial epithelial cells), no nuclear localization was observed. Thus, the human SP-C promoter functions as an ATII-specific DNA nuclear targeting sequence. Restriction of gene expression to desired cell types represents one of the most important challenges to gene therapy today, and the use of specific nuclear import sequences represents a novel strategy for cell-specific expression of transgenes from plasmids.
Cephalothin—A New Antibiotic
Authors: Richard S. Griffith, Henry R. Black
Journal: JAMA (1964)

A new antibiotic, cephalothin, was shown, in vitro, to have a broad spectrum of activity, including penicillin-resistant staphylococci.<i>Pseudomonas</i>strains were totally resistant. Therapeutic concentrations were achieved with doses of 0.5 to 1 gm given intramuscularly every four to six hours or 4 to 6 gm daily in divided dose or by sustained infusion intravenously. Sixty per cent to 90% of the dose appeared in the urine; however, there was no evidence of accumulation or toxicity in patients with poor renal function, possibly because of rapid tissue destruction. Good or excellent clinical results were seen in 51 of 61 infections caused by gram-positive or gram-negative organisms. Patients with a history of penicillin allergy were given cephalothin with no resultant difficulty.
Reply to Neeraj Kumar Goyal, Apul Goel and Rahul Yadav's Letter to the Editor re: Matthias Oelke, François Giuliano, Vincenzo Mirone, Lei Xu, David Cox, Lars Viktrup. Monotherapy with Tadalafil or Tamsulosin Similarly Improved Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia in an International, Randomised, Parallel, Placebo-controlled Clinical Trial. Eur Urol 2012;61:917–25
Authors: Matthias Oelke
Journal: European Urology (2012)
MENIERE'S DISEASE, WITH REPORT OF A CASE.
Authors: JAMES M. BROWN
Journal: JAMA (1898)

The employment of a term as indefinite as "Meniere's Disease" is now generally held to be, in giving title to the subject to which I ask your attention, may call for some explanation or apology, for quoting the words of Sir Wm. B. Dalby: "The term serves more frequently to mark ignorance of the lesion which occasions a series of symptoms, often analogous, but which are under the influence of very different causes." Such apology if called for must be the admitted absence of any designation more definite, and yet generally applicable to all cases of, or the various symptoms met with in, this disease, together with the great diversity of opinion which still obtains in the minds of the profession concerning it. Until we know the exact pathology and are able to separate other analogous diseases with which it may be confounded, it is wiser to hold to the
The Effect of Ancient DNA Damage on Inferences of Demographic Histories
Authors: E. Axelsson, E. Willerslev, M. T. P. Gilbert, R. Nielsen
Journal: Molecular Biology and Evolution (2008)

The field of ancient DNA (aDNA) is casting new light on many evolutionary questions. However, problems associated with the postmortem instability of DNA may complicate the interpretation of aDNA data. For example, in population genetic studies, the inclusion of damaged DNA may inflate estimates of diversity. In this paper, we examine the effect of DNA damage on population genetic estimates of ancestral population size. We simulate data using standard coalescent simulations that include postmortem damage and show that estimates of effective population sizes are inflated around, or right after, the sampling time of the ancestral DNA sequences. This bias leads to estimates of increasing, and then decreasing, population sizes, as observed in several recently published studies. We reanalyze a recently published data set of DNA sequences from the Bison (Bison bison/Bison priscus) and show that the signal for a change in effective population size in this data set vanishes once the effects of putative damage are removed. Our results suggest that population genetic analyses of aDNA sequences, which do not accurately account for damage, should be interpreted with great caution.
Highly sensitive C-reactive protein level predicts recurrence of atrial fibrillation after cardioversion in patients on antiarrhythmic drugs
Authors: Oussama Wazmi, Nassir F. Marrouche, David Martin, Mostafasahin Shaaraoui, Walid Saliba, Eduardo Saad, Mandeep Bhargava, Alejandro Perez-Lugones, Andrea Natele
Journal: Journal of the American College of Cardiology (2003)