tbuckley/cabot-search huggingface dataset:
Abstract 4354: Dihydroartemisinin inhibits mTORC1 signaling in tumor cells.
Authors: Yoshinobu Odaka, Baoshan Xu, Shile Huang
Journal: Cancer Research (2013)

Abstract Dihydroartemisinin (DHA) is a derivative of artemisinin, a natural product isolated from the plant, Artemisia annua. DHA is also the active metabolite of first-generation artemisinin derivatives (artemisinin, artesunate, artemether, etc.). Artemisinins have been clinically used to treat malaria for decades. Recent studies have demonstrated that artemisinin and its derivatives possess anticancer activity. This study was set to investigate the anticancer mechanism of DHA. We found that DHA inhibited proliferation in a spectrum of tumor cells, by arresting cells in G1/G0 and G2/M phases, which was linked to downregulation of cyclin D1, CDK4 and CDC25A, as well as CDK1 and CDC25C expression, respectively. We also observed that DHA induced caspase-dependent apoptosis, which was related to downregulation of survivin, Mcl-1 and Bcl2. As the mammalian target of rapamycin (mTOR) is a master kinase that regulates cell proliferation and survival, we further tested whether DHA inhibits mTOR signaling. Interestingly, we observed that DHA inhibited phosphoryaltion of mTOR and its downstream effector molecules, p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), in a concentration- and time-dependent manner, but did not obviously affect mTORC2-mediated phosphorylation of Akt, which is in contrast to the conventional mTORC1 inhibitor, rapamycin. The results suggest that DHA may represent a novel class of mTORC1 inhibitor, and may execute its anticancer activity primarily by blocking mTOR-mediated signaling pathways in the tumor cells. Citation Format: Yoshinobu Odaka, Baoshan Xu, Shile Huang. Dihydroartemisinin inhibits mTORC1 signaling in tumor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4354. doi:10.1158/1538-7445.AM2013-4354
School Epidemic of Measles
Authors: F. G. Hobson
Journal: BMJ (1938)

One boy stated to have had measles and therefore not protected by serum developed measles, possibly a second attack.* The claim that immune globulin modifies an attack of measles is sustained, but as the author was sceptical of the claims of this preparation 10 c.cm. was employed, although the makers recom- mend no more than 2 c.cm.The single case which received a small dose showed no atteniation.
Functional Effects of Neuropeptide Y Receptors on Blood Flow and Nitric Oxide Levels in the Human Nose
Authors: ANDERS CERVIN, JENNY ÖNNERFÄLT, LARS EDVINSSON, LARS GRUNDEMAR
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The aim of this study was to examine dose-dependent effects of intranasal application of neuropeptide Y (NPY) on nasal mucosal blood flow, blood content, and intranasal nitric oxide (NO) concentration. Blood flow was measured by laser Doppler flowmetry (LDF) and blood content by rhinomanometry. Mucosal biopsies were taken for investigation of Y1 and Y2 receptor mRNA expression, using the reverse transcriptase–polymerase chain reaction (RT–PCR). Intranasal application of NPY evoked a dose-dependent reduction of nasal mucosal blood flow. Maximal vasoconstriction, seen at 12 nmol, was − 37.5 ± 6.2%, p < 0.05 (n = 9). The vasoconstrictive effect developed within 2 to 4 min and lasted > 17 min. NPY evoked a dose-dependent reduction of nasal airway resistance (NAR) on the ipsilateral side. Maximal decrease was − 24.0 ± 10.0% at 12 nmol, p < 0.05 (n = 9). There was a decrease in nasal NO production on the ipsilateral side after application of NPY 12 nmol ( − 7.4 ± 1.2%, p < 0.05, n = 8). RT–PCR products corresponding to Y1 receptor but not Y2 receptor mRNA were obtained from biopsies of the nasal mucosa. In conclusion, NPY is a potent vasoconstrictor in the human nose reducing mucosal blood flow, as well as the blood content. The effect is probably mediated via Y1 receptors. NPY receptor agonists may prove beneficial in the treatment of the congested nose in allergic or vasomotor rhinitis. Cervin A, Önnerfält J, Edvinsson L, Grundemar L. Functional effects of neuropeptide Y receptors on blood flow and nitric oxide levels in the human nose.
Effects of Oral Potassium on Blood Pressure
Authors: Paul K. Whelton
Journal: JAMA (1997)

<h3>Objective.</h3> —To assess the effects of supplementation with oral potassium on blood pressure in humans. <h3>Design.</h3> —Meta-analysis of randomized controlled trials. <h3>Data Sources.</h3> —English-language articles published before July 1995. <h3>Study Selection.</h3> —Thirty-three randomized controlled trials (2609 participants) in which potassium supplementation was the only difference between the intervention and control conditions. <h3>Data Extraction.</h3> —Using a standardized protocol, 2 of us independently abstracted information on sample size, duration, study design, potassium dose, participant characteristics, and treatment results. <h3>Results.</h3> —By means of a random-effects model, findings from individual trials were pooled, after results for each trial were weighted by the inverse of its variance. An extreme effect of potassium in lowering blood pressure was noted in 1 trial. After exclusion of this trial, potassium supplementation was associated with a significant reduction in mean (95% confidence interval) systolic and diastolic blood pressure of-3.11 mm Hg (-1.91 to-4.31 mm Hg) and-1.97 mm Hg (-0.52 to-3.42 mm Hg), respectively. Effects of treatment appeared to be enhanced in studies in which participants were concurrently exposed to a high intake of sodium. <h3>Conclusions.</h3> —Our results support the premise that low potassium intake may play an important role in the genesis of high blood pressure. Increased potassium intake should be considered as a recommendation for prevention and treatment of hypertension, especially in those who are unable to reduce their intake of sodium.
IS EARLY RESECTION OR CONSERVATIVE TREATMENT ADVISABLE IN COXITIS?Read in the Section of Surgery and Anatomy, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May, 1891.
Authors: HERMAN MYNTER
Journal: JAMA (1891)

While our increased knowledge of the pathology of tuberculous joint affections has resulted, in most joints, in earlier operations, in order to remove the local focus before the joint has become totally disorganized, the same cannot properly be said about tuberculous affections of the hip-joint. We still find the same disagreement between the adherents of conservative and operative treatment, and I scarcely say too much when I state that, in the vast majority of cases, excision is still made as<i>ultimum refugium</i>only. Yet even in these cases, a better knowledge of the pathology and consequently improved operative methods, have been followed by decreased mortality and improved functional results. In order to decide the question, it seems proper shortly to study the pathology of coxitis. We formerly believed that tuberculous affections of the hip, or, for that matter, of any other joint, commenced as diffuse inflammations, which went on to
Local Analgesia for Adult Circumcision
Authors: H. L. Rogerson
Journal: BMJ (1944)

UNUSUAL,CASE OF TUBERCULOSISMEIAJORL in appearance, as were the aorta and coronary arteries.The liver was enlarged, and was the seat of many tubercles.These varied in size from 1/4 in. to 1/2 in., and showed a surprising lack of casea- tion.They were in several cases surrounded by necrotic liver tissue and there was little or no fibrosis around the tubercles.The spleen was enlarged to about four times the normal size and was congested.Here again were seen many tubercles similar in size and appearance to those in the liver.There was a fibrinous perisplenitis.The kidneys showed several small tubercles scattered through the organs.The pancreas appeared normal, though there was an enlarged semi- caseous lymph gland near the head.The suprarenals were normal.The oesophagus, stomach, and intestines were also normal in appear- ance.There was little free fluid in the abdominal cavity, and only an occasional small tubercle was present in the peritoneum.Microscopical Examinationi.-Smearstaken from the peribronchial lymph gland and from a tubercle in the liver showed acid alcohol- fast bacilli.Sections of the tubercle in the myocardium revealed a central area of early caseation, surrounded by-endothelioid cells, histiocytes, and small round cells.Scanty giant cells of the Langhans type were present.Acid alcohol-fast bacilli were also found.
Obstetricians should focus on problems
Authors: D. K James
Journal: BMJ (1995)

obstetric team on call.Women with problems will have also received midwifery care but can have a seamless transition to an obstetrician.I believe that there could be no criticism of such a model unless there is a hidden agenda. Hidden agendaAs in many other areas of medicine obstetricians have introduced monitoring and interventionalist strategies to the management of pregnancy and labour without full scientific evaluation.This has led to a medicalisation of normal pregnancy and resulted in an increase in the rate of induction and caesarean sections, many of which could be classified as unnecessary.The hidden agenda of those who propose that obstetricians should not see women with normal pregnancies is not continuity of care and extended choice for women but rather to reduce the level of intervention by keeping women away from obstetricians.It would be much better if women, midwives, and obstetricians all acknowledged that a problem exists.The appropriate studies could then be done to determine which interventions are required for the safest and most acceptable care.If nothing else this approach would have the advantage ofbeing intellectually honest.
Studies of the toxic interactions of disinfection by-products.
Authors: R D Laurie, J P Bercz, T K Wessendarp, L W Condie
Journal: Environmental Health Perspectives (1986)

A large number and variety of compounds are formed in the process of chlorinating drinking water. The classes of compounds formed include trihalomethanes, haloacetic acids, haloacetonitriles, halophenols, and halopropanones. Many of the compounds have been shown to be toxic and are currently being further evaluated by the U.S. Environmental Protection Agency (EPA). One group of the halopropanones found in chlorinated drinking water is the dichloropropanones. The toxicological properties of this group have not been well characterized. In addition, a number of investigators have shown that ketones potentiate the hepatotoxicity of haloalkanes. We conducted a series of studies to explore both the toxicity of the dichloropropanones and their potential interactions with a well-characterized haloalkane, carbon tetrachloride. A variety of toxicological and biochemical endpoints were used to evaluate the toxicity of the dichloropropanones and their interaction with CCl4, including cytochrome P-450 concentration, reduced glutathione levels, pentane generation, serum enzyme activities, and histopathology. Administration of 1,1-dichloropropanone (DCP) resulted in elevated serum enzymes associated with periportal necrosis. Glutathione levels were reduced by the administration of 1,1-DCP; pentane generation was not increased. When 1,1-DCP was given prior to CCl4, the data were consistent with additivity. Administration of 1,3-DCP did not result in elevated serum enzymes, nor was there histopathologic evidence of necrosis. Glutathione levels and pentane generation in the 1,3-DCP-treated groups were the same as those of controls. Inhibition of the toxicologic effects of CCl4 in a dose-related manner was observed when 1,3-DCP was administered prior to CCl4.
Engineering theranostic nanovehicles capable of targeting cerebrovascular amyloid deposits
Authors: Edward K. Agyare, Kristen M. Jaruszewski, Geoffry L. Curran, Jens T. Rosenberg, Samuel C. Grant, Val J. Lowe, Subramanian Ramakrishnan, Anant K. Paravastu, Joseph F. Poduslo, Karunya K. Kandimalla
Journal: Journal of Controlled Release (2014)
Deaths from measles in England and Wales, 1970-83.
Authors: C L Miller
Journal: BMJ (1985)

Le nombre de morts dues a la rougeole etait de 39 en 1970 et de 17 en 1983, mais le pourcentage par rapport aux nombres de rougeoles declarees n'a pas diminue. La cause de mort est souvent une bronchopneumonie, ou une encephalite. L'encephalite ne frappe pas seulement les enfants physiquement ou mentalement anormaux a la naissance. Une vaccination plus precoce pourrait prevenir ces complications mais la presence des anticorps maternels pose des problemes
Mortal Lessons: Notes on the Art of Surgery
Authors: Lester S. King
Journal: JAMA (1977)

Thebook forum inThe Journalhas space to review only about 20% of the books we receive. I had originally placed Dr Selzer's book in the 80% category. However, after seeing numerous reviews in the lay press, most of them highly commendatory, I felt impelled to place on record a point of view diametrically opposite. Dr Selzer, who has published abundantly in the lay press, has here produced a collection of essays directed to the laymen, but all dealing in one way or another with medicine. In subject matter he ranged from anatomical, physiological, and surgical topics, presented for lay reading, frequently with "philosophic" overtones, to anecdotal reminiscences of his childhood. One review compared Selzer to Sir Thomas Browne, a comparison that makes me writhe. Browne is a magnificent stylist, although in a manner now outmoded. Selzer, as a stylist, conveys the impression that he has not too much
Identification of Aryl Hydrocarbon Receptor as a Putative Wnt/β-Catenin Pathway Target Gene in Prostate Cancer Cells
Authors: Dennis R. Chesire, Thomas A. Dunn, Charles M. Ewing, Jun Luo, William B. Isaacs
Journal: Cancer Research (2004)

Recent genetic and functional analyses have implicated the wnt/beta-catenin signaling pathway in prostate cancer (CaP) pathogenesis. Thus, there is much interest in understanding the consequences of wnt signaling in CaP; target gene expression is one important area of inquiry and is the focus of this report. Adenoviral-mediated overexpression of a mutant, hyperactive form of beta-catenin in CWR22-Rv1 CaP cells led to increased aryl hydrocarbon receptor (AhR, or dioxin receptor) and transmembrane protein 2 RNA transcript expression, as detected by cDNA-microarray analyses. Validating these results, reverse transcription-PCR assays demonstrated that in CWR22-Rv1 cells as well as in LAPC-4 CaP cells, increased putative target gene RNA expression occurs with transient overexpression of mutant beta-catenin, treatment of cells with lithium chloride, or with wnt3a-conditioned medium, three distinct modes of experimental wnt/beta-catenin pathway activation. This beta-catenin-associated expression of AhR and transmembrane protein 2 does not require de novo protein synthesis and may only involve a certain subset of CaP cell lines. Western and immunofluorescence analyses were undertaken to assess the relationship between the wnt/beta-catenin-stimulated increase in AhR transcripts and AhR protein expression; we provide evidence that an association exists whereby up-regulation of AhR RNA by wnt or beta-catenin is coupled with augmented AhR protein levels. Intriguingly, these studies also demonstrated that nuclear beta-catenin staining may not be a sole deciding factor when predicting the status of wnt/beta-catenin signaling in CaP cells. Finally, the extent to which wnt signaling may synergize with an environmental agonist of AhR (2,3,7,8-tetrachlorodibenzo-p-dioxin) to potentiate AhR transcriptional activity was examined. Considering previous work linking AhR to processes of development and carcinogenesis, our data may highlight one particular role for wnt/beta-catenin signaling in prostate tumor biology.
Individual and Environment: Monozygotic Twins Reared Apart
Authors: Winifred F. Storey
Journal: JAMA (1980)

Beginning in 1954, the author studied 12 pairs of monozygotic twins, aged 22 to 77 years, who had been reared apart since early childhood. The clinical research extended over a two- to four-year interval for each twin pair. The methods included indepth serial medical and psychiatric interviews, EEGs, ECGs, chest films, Wechsler-Bellevue intelligence measurements, and personality profiles as interpreted from the Rorschach test. To assist in confirming zygosity, blood groups were documented.  The current publication is a revised edition of the original, published in 1965, with a follow-up of the twins 25 years after the initiation of the investigation.  The results are discussed in four categories: health in general, physical illnesses, level of intelligence and personality profile, and presence or absence of mental illness.  Among the similarities between the twins of each pair are EEGs, level of functioning intelligence, and presence or absence of migraine headache. However, personality profiles showed
DETECTION OF NATURALLY OCCURRING OSTEOSARCOMA IN DOG WITH RADIOIODINATED FAB2 FRAGMENT OF MONOCLONAL ANTIBODY
Authors: G Matte, D Haines, A A Wilkinson, C J Chmieloweic, O Bruland
Journal: Clinical Nuclear Medicine (1991)

S of the Society of Nuclear Medicine in Canada and Prairie Provinces Chapter, SNM Conjoint Meeting: PDF Only
US blog questions drug company funding of continuing education for journalists
Authors: J. H. Tanne
Journal: BMJ (2010)

A US blog has questioned whether journalists might be influenced by accepting “all expenses paid” fellowships to attend an educational conference on cancer organised by the US National Press Foundation but sponsored by Pfizer.

Pfizer is providing unrestricted funding of $80 000 (£52 000; €62 000) to the US National Press Foundation, a non-profit charitable organisation that provides continuing educational programmes for journalists, to sponsor 15 US journalists to attend the foundation’s four day educational programme on cancer being held in Washington, DC, from 17 to 20 October (http://nationalpress.org/programs-and-resources/program/cancer-issues-2010/).

In his recent Pharmalot blog Ed Silverman, a journalist, asked whether journalists might be influenced by a drug company sponsored but apparently independent educational programme in the way that doctors might be (www.pharmalot.com). “The arrangement is generating a bit of heat in some circles, given sensitivities over perceptions of conflicts of interest,” he said.

Gary Schwitzer, …
It All Started with Hippocrates: A Mercifully Brief History of Medicine
Authors: LLOYD G. STEVENSON
Journal: JAMA (1966)

Actually it didn't start with Hippocrates at all. It began with the dawn of history. In fact it began shortly before dawn, at about 3:00 A.M., when the first Stone Age doctor was routed from  bed.... Pre-Hippocratic, too, was Thoth,  ibis-headed god with a lisp, and great Apollo. (Apollo was not present at  shrines but worked through an answering service.) As for Aesculapius, his fame traveled to the remotest corners of Greece. The legends of Hippocrates are fascinating. One is that he never gave a thought to money. Another is that he admitted  errors. The reader should keep in mind that these are legends. There are, however, some double-Armoured truths in the same chapter. The Hippocratic doctors were itinerant. ( With Hippocrates wandering around lookfor patients and patients wandering around looking for Hippocrates, there was a good deal of confusion.) The vis medicatrix naturae was recognized and
HYPONATREMIA IS ASSOCIATED WITH DIURETIC RESISTANCE AND A HIGHER INCIDENCE OF WORSENING RENAL FUNCTION IN PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE
Authors: Tien M.H. Ng, Diana X. Cao, Komal A. Patel, Yee May Wong, Megha Prasad, Uri Elkayam
Journal: Journal of the American College of Cardiology (2012)
Introduction to Clinical Investigation
Authors: Kenneth G. Kohlstaedt
Journal: JAMA (1964)

THE INITIAL clinical trial is a crucial matter in the development of a new drug. The risk inherent in its first use in man, and the need to obtain a true evaluation of its action before large sums of money are invested in materials, make it imperative that the initial trial be a well-controlled study. It should be conducted by a physician who is trained in this form of clinical research and the investigation should be performed in an environment that permits accurate observations. Years of effort in research and testing which may have preceded the first clinical trial will have been wasted if the first tests in man are not appraised accurately. The physician who administers a new compound has a responsibility to the patient or volunteer who will be taking the drug. It is necessary, therefore, that all available information be made known to the physician before he undertakes an
DISLOCATION OF THE MIDDLE CUNEIFORM BONE
Authors: Frank Warner
Journal: JAMA (1918)

Dislocation of the middle cuneiform bone occurs so rarely that instances of its occurrence should be reported. Its rarity adds to the difficulty of recognizing the condition; but unless it is recognized, impaired usefulness of the foot will result. Stimson<sup>1</sup>was able to collect only seven instances of separate dislocations of the middle cuneiform bone, and eleven of fractures. All three cuneiform bones have been displaced together, and the second and third likewise. March 2, 1917, V. G. E., aged 28, a railway conductor, while wearing a pair of heavy work shoes with extra thick, double soles, had his left foot run over by an empty dump car. The skin was not lacerated, but there was a bony protuberance on the dorsal surface, over the situation of the middle cuneiform. A diagnosis of dislocation of this bone was confirmed by roentgenoscopy. Failing to reduce the dislocation, first without an
A marked increase in serum soluble Fas ligand in drug-induced hypersensitivity syndrome
Authors: M. Tohyama, Y. Shirakata, K. Sayama, K. Hashimoto
Journal: British Journal of Dermatology (2008)

Journal Article A marked increase in serum soluble Fas ligand in drug‐induced hypersensitivity syndrome Get access M. Tohyama, M. Tohyama Department of Dermatology, Ehime University Graduate School of Medicine, Toon‐city, Ehime 791‐0295, Japan E‐mail: tohm@m.ehime‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Y. Shirakata, Y. Shirakata Department of Dermatology, Ehime University Graduate School of Medicine, Toon‐city, Ehime 791‐0295, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Sayama, K. Sayama Department of Dermatology, Ehime University Graduate School of Medicine, Toon‐city, Ehime 791‐0295, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Hashimoto K. Hashimoto Department of Dermatology, Ehime University Graduate School of Medicine, Toon‐city, Ehime 791‐0295, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 159, Issue 4, 1 October 2008, Pages 981–984, https://doi.org/10.1111/j.1365-2133.2008.08750.x Published: 01 October 2008