tbuckley/cabot-search huggingface dataset:
Charles Scott Sherrington 1857–1952
Authors: Henry R. Viets
Journal: New England Journal of Medicine (1952)

THE death of Sir Charles Sherrington on March 4, 1952, in his ninety-fifth year, brings to a close a long life devoted to research and teaching in physiology with, at the same time, leadership in a broad field of political, artistic, intellectual and humanitarian endeavors. Knighted in 1922; winner of the Nobel Prize, with Edgar Adrian, in 1932; Fellow and one-time President of the Royal Society, Sir Charles received the Order of Merit, one of Britain's highest awards, more than a quarter-century ago. He gave the Silliman Lectures at Yale in 1904 and the Dunham Lectures at Harvard in 1927. . . .
A Lecture on VASOVAGAL SYNCOPE AND THE CAROTID SINUS MECHANISM
Authors: T. Lewis
Journal: BMJ (1932)

fni the present article a form of fainting is described for which the term " vasovagal syncope " will be found most a.ppropriate.It forms a common and interesting disturbance of a transient kind.It will be described and discussed in relation to a mechanism that has been under close investigation in recent years.There is another and distinct condition with which terminology tends to con- fuse it-namely, what I shall call for convenience " Gowers's syndrome "; there is also a third condition, probably comprising a vasomotor disturbance-namely, " Nothnagel's syndrome," and thought by some to be identical with Gowers's syndrome.The available evidence relating to these last two maladies will be considered sufficiently to allow us to see what there is in it of significance from the standpoint of the vascular system.
Clinical Lecture on a Case of Tubercle of the Iris and Ciliary Body
Authors: J. R. Wolfe
Journal: BMJ (1882)

THE BR1fT2SR MEDICAL 7OURARAL 299 been duly explained it was eed that the opertion should be done.I cut through thie neck of the mur with Adams's saw, enconteritng some little delay on account of the hardnes of the bone, and possibly from having got too close to the shaft, that is, not sufficiently across the neck.The operation was done under Lister's precautions.When the section of the bone was complete, I divided the tendon of the adductor longes, and those of the sartorius and tensor vaglnm femoris.We were able at once to put the limb in much better position; and, subsequently, when the wound was healed, this was still further Improved.No inflam- mationoccurredabout thewound, and he made anuninterrupted recovery.We did not succeed in preventing union of the bone at the site of section, and you now see the ultimate condition obtained.The man lhas mince been able to walk erect; and he hu now, for six years, been en- gaged in his former occupation with greatly increaed comfort.One drawback I must mention; and it is, indeed, on account of this ft.-These woodcuts are copied from photographs to show the condition before and after operation.that we now have him again under care.He had, two years ago, an acute abscess in his buttock.This was four yeats after the operation, and not apparently in any direct connection with it.The abscess did not lead to bare bone, and, after it was opened, sound healing oc- curred; but he now, two years later, comes to us again, complaining of pain in the same position, and fearing that another abscess is imminent.may state that I have under observation, In private, a very similar case, in which one hip has been ankylosed for many years.The patient is in robust health, and yet occasionally-that is, once in three or four ears-deep-seated abscesses occur, after the evacuation of which sound ealing again takes place.I do not know of any cause for these abs-
Production of lung carcinomas in C57BL mice exposed to a cigarette smoke and air mixture.
Authors: R J Harris, G Negroni
Journal: BMJ (1967)

There is no doubt that the tar produced by condensing cigarette smoke is carcinogenic for mice (see Day, 1967).However, lung epithelium differs from the skin and the condensate differs from fresj cigarette smoke in, for example, the absence of the gaseous components.It appeared worth while to us, therefore, to attempt to produce lung carcinomas in mice by allowing them to breathe a mixture of cigarette smoke and air for a prolonged period.Stewart and Herrold (1962), in a "critique of experiments on attempts to induce cancer with tobacco derivatives," review negative mouse inhalation studies by Lorenz et al. (1943) and by Dunn (1943) using Strong A mice (a strain with a 90% spontaneous incidence of lung adenomas at 18 months of age).Essenberg (1952), however, had exposed the same strain of mice to cigarette smoke for 12 to 14 months in a ventilated chamber and increased the incidence of papillary adeno- carcinomas in these mice.Milhlbock (1955) also claimed to have increased the incidence of lung tumours in a hybrid 020 xDBA strain of mouse by puffing smoke from cigarettes into a sealed cage every two hours each day.We believed, however, that we should use a strain such as C57BL, which apparently have a predominant gene for resistance to the induction of lung tumours (Bloom and Falconer, 1964), and in which Peacock and Peacock (1966) described only one deep-seated spontaneous papillary adenoma in an 817-days-old male.We were thus aware of many negative results, but were not convinced that these experiments had been conducted under the optimum conditions.In most cases (except for Lorenz et al.) there was no evidence that the animals were actually taking the smoke droplets into their lungs.Most observers agree that lung cancer in man is multi- factorial, and that of these other factors chronic respiratory disease (bronchitis, bronchiolitis, and chronic pneumonitis) is probably the most important.There are two ways in which lung disease might contribute to the occurrence of lung cancer.Firstly, the diseased lung might be less able to prevent retention of particulate carcinogens, such as smoke droplets ; and, secondly, infectious agents such as respiratory viruses and mycoplasma might themselves produce areas of cellular proliferation which were susceptible to the effects of inhaled chemical (or viral) carcinogens.
Abstract IA16: Engineered T cell therapies for cancer.
Authors: Carl H. June
Journal: Cancer Research (2013)

Abstract Chimeric antigen receptors (CARs) combine an antigen recognition domain of a specific antibody with a intracellular signaling domains into a single engineered protein. CD19 is an ideal target for CARs since expression is restricted to normal and malignant B cells. In preclinical studies, inclusion of the CD137 (4-1BB) signaling domain results in remarkable antitumor activity and in vivo persistence of anti-CD19 CARs. We have previously reported dramatic in-vivo expansion, persistence and anti-tumor activity of CAR modified autologous T cells targeted to CD19 (CART19 cells) in 3 patients with CLL with relatively short follow up (Porter, et al NEJM 2011; Kalos et al Sci Trans Med 2011). Currently, 11 patients have been treated with CART19 cells. There were 9 adults (median age 65 years (range 51-78)) treated for relapsed, refractory and high risk CLL and two pediatric cases treated for relapsed refractory pre-B cell ALL. CLL patients had received a median of 5 prior regimens excluding single agent rituxumab (range 2-10) and all had active disease at the time of cell infusion. The pediatric patients with ALL had chemotherapy refractory relapse, and one was resistant to allogeneic transplantation and CD19 directed blinotumomab. A median of 7.5 x 10^8 total cells (range 1.7-50) corresponding to 1.45 (range 0.14-5.9 x 108) genetically modified cells were infused. In the patients in complete remission, CAR modified CART19 cells are detectable in the peripheral blood by flow cytometry at the most recent follow up for at least 2 years. All patients in CR have B cell aplasia. No patient with CR has progressed. Citation Format: Carl H. June. Engineered T cell therapies for cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA16.
Readers want transparency in link between doctors and drug firms
Authors: L. Eaton
Journal: BMJ (2003)

Ninety six per cent of those voting in a poll conducted by the BMJ on its website (bmj.com) would like to see all financial relationships between doctors and drug companies conducted with transparent contracts that are disclosed to patients.​patients.




Table 1

Responses (percentage of respondents) to the eight questions in BMJ poll


		Yes	No	Don't know
Would you like doctors to stop seeing drug company representatives, replacing them with more independent sources of health information? 	79	15	4	
Would you like doctors to stop receiving all forms of direct and indirect gifts from drug companies? 	84	13	2	
Would you like industry-funded education of doctors replaced by education funded by more independent sources? 	84	9	4	
Would you like doctors' professional associations and their peer-reviewed journals to reduce their reliance on industry funding to specified maximum levels? 	85	7	5	
Would you like all financial relationships between doctors and drug companies conducted with transparent contracts that are disclosed to patients and the public? 	96	1	1	
Would you like mechanisms that genuinely create more distance and independence between doctor/researchers and their research sponsors? 	83	9	5	
Would you like government/public agency advisory panels, which are responsible for independent assessment of medical products or health policies, to reduce their reliance on doctors with financial ties to drug companies? 	87	6	4	
Would you like to see these sorts of changes become the basis of a charter for a new relationship between doctors and drug companies? 	90	5	3	


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A total of 1479 people responded to the questions. The poll was conducted after the BMJ published its theme issue “Time to Untangle Doctors from Drug Companies” (31 May) (see also www.bmj.com/collections/specials.shtml).
Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts
Authors: Sergio A. Quezada, Tyler R. Simpson, Karl S. Peggs, Taha Merghoub, Jelena Vider, Xiaozhou Fan, Ronald Blasberg, Hideo Yagita, Pawel Muranski, Paul A. Antony, Nicholas P. Restifo, James P. Allison
Journal: The Journal of Experimental Medicine (2010)

Adoptive transfer of large numbers of tumor-reactive CD8+ cytotoxic T lymphocytes (CTLs) expanded and differentiated in vitro has shown promising clinical activity against cancer. However, such protocols are complicated by extensive ex vivo manipulations of tumor-reactive cells and have largely focused on CD8+ CTLs, with much less emphasis on the role and contribution of CD4+ T cells. Using a mouse model of advanced melanoma, we found that transfer of small numbers of naive tumor-reactive CD4+ T cells into lymphopenic recipients induces substantial T cell expansion, differentiation, and regression of large established tumors without the need for in vitro manipulation. Surprisingly, CD4+ T cells developed cytotoxic activity, and tumor rejection was dependent on class II–restricted recognition of tumors by tumor-reactive CD4+ T cells. Furthermore, blockade of the coinhibitory receptor CTL-associated antigen 4 (CTLA-4) on the transferred CD4+ T cells resulted in greater expansion of effector T cells, diminished accumulation of tumor-reactive regulatory T cells, and superior antitumor activity capable of inducing regression of spontaneous mouse melanoma. These findings suggest a novel potential therapeutic role for cytotoxic CD4+ T cells and CTLA-4 blockade in cancer immunotherapy, and demonstrate the potential advantages of differentiating tumor-reactive CD4+ cells in vivo over current protocols favoring in vitro expansion and differentiation.
Robert Thomas Paul
Authors: John Quarrie
Journal: BMJ (2006)

Former general practitioner Loch Aline, Scotland (b 1939; q Leeds 1963), died from a heart attack on 15 February 2006.

After preregistration posts in Keighley, Yorkshire, Bob joined a group practice in Barnoldswick for three years. He then worked in Ontario for four years, where he developed an interest in anaesthetics. Returning to the United Kingdom in 1971, he worked in Whitby for 14 years before moving to Loch Aline in 1986. He retired on health grounds in 1994, moving to France and to the Scottish Borders in 2001. He leaves a wife, five children, and 11 grandchildren.
Relation of the "Anti-Stiffness Factor" to Collagen Disease and Calcinosis
Authors: J. Lansbury, L. W. Smith, R. Wulzen, W. J. Van Wagtendonk
Journal: Annals of the Rheumatic Diseases (1950)

The Relation of the Anti-Stiffness Factor to Collagen Disease and CalcinosisThe " anti-stiffness factor " is a fat-soluble vitamin whichregulatesphosphorus metabolism.The object of this communication is to report studies on the possible relations of the anti-stiffness factor to human disease.Since none of the work on the anti-stiffness factor has appeared in journals devoted to clinical matters, the essential experimental findings are briefly summarized below.Sources and Nature of the Anti-Stiffness Factor.-Thecrude sources of the antistiffness factor are green vegetables, raw cream, unheated molasses, and raw sugar- cane juice.The nature of the active principle is still unknown.Active fractions, however, are fat soluble.Reliable assay is difficult; Gouley found that methylvinyl-ketone had some anti-stiffness activity, but this has not been confirmed as the active principle.Oleson and others (1947), and Petering and others (1948), suggested ergostanyl acetate and alpha-ergostanyl acetate respectively as the active principle.Van Wagtendonk and Wulzen (1943) isolated a fat-soluble fraction from raw cream curative in doses of 0 1 ,ug., and (1946) a crystalline substance from molasses and cane juice which was active in doses of 0 * 002 jig.Ross and others (1949) have recently presented evidence for the presence of a steroid compound in cane juice which exhibits anti-stiffness activity.Animals Lacking Anti-Stiffness Factor Smith and Elvove (1929) produced calcification in animals by a diet high in phosphorus and ergosterol, and Stephens and Barr (1933) did the same by a diet high in calcium, phosphorus, and acid.But the production of calcific deposits by a deficient diet dates from the work of Wulzen and Bahrs (1936); they reported that guinea-pigs maintained for months on a diet lacking in green vegetables developed general muscle stiffness and pain on movement of the carpal joints.As the condition progresses, the skeletal muscles atrophy, the animal becomes rigid in extension with flaring of the rib cage, and ultimately there are deposits of calcium salts between the muscle fibres, around the joints, and under the skin in the majority of the animals.These may break down and discharge calcium salts.Late manifestations include widespread deposits of calcium in and around blood vessels, and in parenchymal tissues such as the stomach and intestines.In some instances the skin is adherent to the underlying structures.In advanced cases there may be 97 2
The promise of cloning for human medicine
Authors: R. Winston
Journal: BMJ (1997)

The promise of cloning for human medicineNot a moral threat but an exciting challenge T he production of a sheep clone, Dolly, from an adult somatic cell 1 is a stunning achievement of British science.It also holds great promise for human medicine.Sadly, the media have sensationalised the implications, ignoring the huge potential of this experiment.Accusations that scientists have been working secretively and without the chance for public debate are invalid.Successful cloning was publicised in 1975, 2 and it is over eight years since Prather et al published details of the first piglet clone after nuclear transfer. 3issing from much of the debate about Dolly is recognition that she is not an identical clone.Part of our genetic material comes from the mitochondria in the cytoplasm of the egg.In Dolly's case only the nuclear DNA was transferred.Moreover, we are a product of our nurture as much as our genetic nature.Monovular twins are genetically closer than are artificially produced clones, and no one could deny that such twins have quite separate identities.Dolly's birth provokes fascinating questions.How old is she?Her nuclear DNA gives her potentially adult status, but her mitochondria are those of a newborn.Mitochrondia are important in the aging process because aging is related to acquired mutations in mitochondrial DNA, possibly caused by oxygen damage during an individual's life. 4Experimental nuclear transfer in animals and in human cell lines could help elucidate mechanisms for many of these processes.Equally extraordinary is the question concerning the role of the egg's cytoplasm in mammalian development.Once the quiescent nucleus had been transferred to the recipient egg cell, developmental genes expressed only in very early life were switched on.There are likely to be powerful factors in the cytoplasm of the egg that make this happen.Egg cytoplasm is perhaps the new royal jelly.Studying why and how these genes switch on would give important information about both human development and genetic disease.Research on nuclear transfer into human eggs has immense clinical value.Here is a model for learning more about somatic cell differentiation.If, in due course, we could influence differentiation to give rise to targeted cell types we might generate many tissues of great value in transplantation.These could include skin and blood cells, and possibly neuronal tissue, for the treatment of injury, for bone marrow transplants for leukaemia, and for degenerative diseases such as Parkinson's disease.One problem to be overcome is
CELLULAR MECHANISMS OF PROTEIN METABOLISM IN THE NEPHRON
Authors: Jean Oliver, Muriel MacDowell
Journal: The Journal of Experimental Medicine (1958)

1. The exaggeration of "hyaline droplet" formation observed in the renal lesion of epidemic hemorrhagic fever when treated with the infusion of large amounts of human serum albumin and the histochemical characteristics of the droplets so formed afford evidence towards their identification with the protein absorption droplets of experimental procedures and with those that occur in other renal diseases. 2. Protein absorption droplets (hyaline droplets) are the visible aspect of pathological modifications of a physiological process; i.e., the continuing reabsorption of plasma proteins by the proximal convolutions. 3. The mitochondria of the renal cells are directly involved in both the physiological and the abnormal reabsorption and disposal of the plasma proteins; the absorption droplets are a complex of reabsorbed proteins and mitochondrial substances and enzymes; they result whenever disposal is at a rate insufficient to prevent accumulation. 4. Failure of intracellular disposal of reabsorbed protein is determined by (a) the quantitative and qualitative characteristics of the protein and (b) by the functional state of renal cell. 5. Various factors in renal disease that result in disturbances of reabsorption and of intracellular disposal, both with and without droplet formation, are described.
A randomized trial comparing transjugular intrahepatic portosystemic stent-shunt with variceal band ligation in the prevention of rebleeding from esophageal varices
Authors: R Jalan, E H Forrest, A J Stanley, D N Redhead, J Forbes, J F Dillon, A J MacGilchrist, N D Finlayson, P C Hayes
Journal: Hepatology (1997)

The aim of this study was to compare transjugular intrahepatic portosystemic stent-shunt (TIPSS) with variceal band ligation (VBL) in the secondary prophylaxis of esophageal variceal hemorrhage in patients with cirrhosis. Fifty-eight patients with cirrhosis who presented with the first episode of esophageal variceal hemorrhage were randomized to TIPSS (31) or VBL (27), 24 hours after control of bleeding. Shunt function was assessed after 1 month and then at 6 monthly intervals thereafter. VBL was performed weekly until variceal eradication, and then at 3 months, 6 months, and yearly thereafter. Mean follow-up in the TIPSS group was 15.7 (±10.2) months; in the VBL group, it was 16.8 (±10.9) months. Results for rebleeding and mortality were analyzed on an intention-to-treat basis and using the Kaplan-Meier method. The frequency and the severity of variceal rebleeding was significantly lower in the TIPSS group (9.8%), compared with the VBL group (51.9%) ( P &lt; .0006). Although mortality rates were not significantly different, 8 of the patients who rebled in the VBL group required TIPSS therapy for uncontrolled bleeding. No significant differences were found in the frequency of other complications such as encephalopathy and sepsis. Patients in the VBL group required significantly greater time in the intensive care unit during the period of this study (&lt;0.03). The total direct cost of treatment incurred was pound sterling 1,373 ($2,200) per patient, the cost being less in the patients treated with TIPSS compared with VBL. The results of this study show that TIPSS is superior to VBL for the secondary prophylaxis of variceal hemorrhage in patients with cirrhosis.
Treatment strategies for prostate cancer
Authors: R. W. Switzer
Journal: JAMA (1993)

To the Editor.  —This letter is written in regard to the two ghastly articles on the treatment of prostate cancer you published in the May 26, 1993, issue of JAMA .  The first article on radical prostatectomy 1 purports to show that the recent increase in this procedure has not changed the death rate from this disease and then quotes death rates for the 15 years prior to the increase to substantiate this. The important period will be 15 to 20 years after surgery, not before. The authors do not seem to understand that a sea change has occurred in the diagnosis of prostate cancer because of the advent of the PSA test and the availability of ultrasound-guided biopsy.  The article by Fleming et al 2 on clinically localized prostate cancer creates a model for treatment based on assumptions, estimates, and assignments, many of which are spurious and all of which
Abstract 723: Acquired resistance to PLX4720 involves both ERK re-activation and suppression of BH3-only proteins in human melanoma cells
Authors: Yongping Shao, Andrew E. Aplin
Journal: Cancer Research (2011)

Abstract B-RAF is mutated to a constitutively active form in 8% of human cancers. Tumors harboring mutant B-RAF are often dependent on B-RAF-MEK-ERK1/2 signaling for the maintenance of malignant properties. Evidence for oncogene addiction has been underscored in early phase clinical trials in which the RAF inhibitor, PLX4032/RG7204, caused partial or complete responses in 81% of mutant B-RAF harboring melanoma patients. However, the average duration of response was 7-8 months with the majority of patients relapsing, indicating the acquisition of resistance to PLX4032. Since understanding the mechanisms of resistance will drive the design of future combinatorial trials, we undertook an in vitro analysis of melanoma cell acquired resistance to PLX4720, the tool compound for PLX4032. Through continuous culture in the presence of PLX4720, we developed mutant B-RAF melanoma cell populations that display resistance to B-RAF inhibitors. Resistance was associated with a partial re-activation of ERK1/2 signaling, recovery of G1/S cell cycle events, and suppression of BH3-only proteins, Bim-EL and Bmf, in the presence of PLX4720. Preventing the ERK1/2 re-activation with MEK inhibitors blocked G1-S cell cycle events but failed to induce apoptosis or up-regulate Bim-EL and Bmf levels. These data indicate that acquired resistance to PLX4032/4720 likely involves ERK1/2 pathway re-activation and ERK1/2-independent silencing of BH3-only protein up-regulation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 723. doi:10.1158/1538-7445.AM2011-723