tbuckley/cabot-search huggingface dataset:
The metalloprotease-disintegrin ADAM8 contributes to temozolomide chemoresistance and enhanced invasiveness of human glioblastoma cells
Authors: Fangyong Dong, Michael Eibach, Jörg W. Bartsch, Amalia M. Dolga, Uwe Schlomann, Catharina Conrad, Susanne Schieber, Oliver Schilling, Martin L. Biniossek, Carsten Culmsee, Herwig Strik, Garrit Koller, Barbara Carl, Christopher Nimsky
Journal: Neuro-Oncology (2015)

Despite multimodal treatment, glioblastoma (GBM) therapy with temozolomide (TMZ) remains inefficient due to chemoresistance. Matrix metalloproteinase (MMP) and a disintegrin and metalloprotease (ADAM), increased in GBM, could contribute to chemoresistance and TMZ-induced recurrence of glioblastoma. TMZ inducibility of metalloproteases was determined in GBM cell lines, primary GBM cells, and tissues from GBM and recurrent GBM. TMZ sensitivity and invasiveness of GBM cells were assessed in the presence of the metalloprotease inhibitors batimastat (BB-94) and marimastat (BB-2516). Metalloprotease-dependent effects of TMZ on mitochondria and pAkt/phosphatidylinositol-3 kinase (PI3K) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) pathways were analyzed by fluorescence activated cell sorting, morphometry, and immunoblotting. Invasiveness of GBM cells was determined by Matrigel invasion assays. Potential metalloprotease substrates were identified by proteomics and tested for invasion using blocking antibodies. TMZ induces expression of MMP-1, -9, -14, and ADAM8 in GBM cells and in recurrent GBM tissues. BB-94, but not BB-2516 (ADAM8-sparing) increased TMZ sensitivity of TMZ-resistant and -nonresistant GBM cells with different O6-methylguanine-DNA methyltransferase states, suggesting that ADAM8 mediates chemoresistance, which was confirmed by ADAM8 knockdown, ADAM8 overexpression, or pharmacological inhibition of ADAM8. Levels of pAkt and pERK1/2 were increased in GBM cells and correlated with ADAM8 expression, cell survival, and invasiveness. Soluble hepatocyte growth factor (HGF) R/c-met and CD44 were identified as metalloprotease substrates in TMZ-treated GBM cells. Blocking of HGF R/c-met prevented TMZ-induced invasiveness. ADAM8 causes TMZ resistance in GBM cells by enhancing pAkt/PI3K, pERK1/2, and cleavage of CD44 and HGF R/c-met. Specific ADAM8 inhibition can optimize TMZ chemotherapy of GBM in order to prevent formation of recurrent GBM in patients.
The Lung: Physiologic Basis of Pulmonary Function Tests
Authors: Herbert P. Wiedemann
Journal: JAMA (1987)

<i>The Lung</i>, now in its third edition, first appeared 30 years ago with the intent "to explain in simple words and diagrams those aspects of pulmonary physiology that are important to clinical medicine." In the second edition, expanded coverage was given to pathophysiology and clinical cases. The third edition eliminates most of the clinical material, thereby returning<i>The Lung</i>to its original scope and concept as a monograph focusing on the scientific basis of pulmonary function tests. As in the earlier volumes, however, the authors continue to target the current edition to clinicians, medical students, and auxiliary medical professionals, rather than pulmonary physiologists. Written by distinguished and venerable authors and honed by three decades of existence,<i>The Lung</i>is received with lofty expectations. The reader anticipates a classic textbook that should stand apart from an ever-enlarging and crowded field of competitors. In large measure,<i>The Lung</i>fulfills its promise, but
Targeted Delivery of Protein Toxins: Delivery of Ricin Toxin A‐Chain by Peptide‐Targeted Mesoporous Silica Nanoparticle‐Supported Lipid Bilayers (Adv. Healthcare Mater. 3/2012)
Authors: Katharine Epler, David Padilla, Genevieve Phillips, Peter Crowder, Robert Castillo, Dan Wilkinson, Brian Wilkinson, Cameron Burgard, Robin Kalinich, Jason Townson, Bryce Chackerian, Cheryl Willman, David Peabody, Walker Wharton, C. Jeffrey Brinker, Carlee Ashley, Eric Carnes
Journal: Advanced Healthcare Materials (2012)

Mesoporous silica nanoparticle-supported lipid bilayers, or “protocells”, are loaded with ricin toxin A-chain (RTA) and targeted to hepatocellular carcinoma (HCC) with a peptide (SP94) that binds to unknown HCC surface antigen(s). RTA-loaded, SP94-targeted protocells are selectively internalized by HCC and release encapsulated RTA upon endosome acid-ification. An endosomolytic peptide (H5WYG), present on the protocell's supported lipid bilayer, disrupts endosomal membranes, releasing RTA into the cytosol of HCC cells. As described by Eric Carnes, Carlee Ashley, and co-workers on page 348, RTA-loaded, SP94-targeted protocells kill HCC at a RTA concentration of 30 pM without affecting the viability of non-cancerous cells. In the cover image, protocells modified with SP94 (red), H5WYG (blue), and PEG (green) are shown interacting with an HCC cell.
NOTE ON A SKIN REACTION IN PNEUMONIA
Authors: Richard Weil
Journal: The Journal of Experimental Medicine (1916)

The present paper describes the results observed when pneumococcus antigen, prepared in the same way as for the anaphylactic experiments described in the preceding article, 1 was injected intracutaneously into a series of pneumonia patients, and into controls.The same method has been employed by Clough, 2 who reached the conclusion that these injections had in general an irritant effect, and that no sharp differences could be shown to exist between pneumonia cases and controls.The present observations do not coincide with those of Clough, but it seems likely that the divergence in results may possibly be due to a difference in the composition of the antigen employed.A very strong pneumococcus extract possesses primarily irritative properties, and sets up reactions independently of any immunological response.In Clough's work the dried and ground residue of a twenty-four to thirty-six hour culture was extracted at 37 ° C. for eighteen hours.The two hour autolysate employed in the present study is very much weaker than Clough's extract.The method of injection was intracutaneous, and the site chosen was the interscapular region.The autolysate, prepared as described in the preceding paper by Torrey and Weil, was kept in the ice box, and was never used more than one week after its preparation.During this period no change could be detected in its effects when injected into the skin.Not infrequently it happens that a sediment forms in the tubes containing the autolysate; this was not disturbed, but the supernatant fluid was carefully drawn off for the tests.As a rule, the autolysate has a faint whitish, opalescent appearance.The amount injected varied from 0.1 to 0.2 cc., depending on the texture of the
Management of heartburn not responding to proton pump inhibitors
Authors: R Fass, D Sifrim
Journal: Gut (2009)

Patients with gastro-oesophageal reflux disease (GORD) who are not responding to proton pump inhibitors (PPIs) given once daily are very common. Various underlying mechanisms have been shown to contribute to the failure of PPI treatment. These include weakly acidic reflux, duodenogastro-oesophageal reflux, residual acid reflux and functional heartburn, as well as others. Diagnostic evaluation of patients with GORD who have failed PPI treatment may include an upper endoscopy, pH testing and oesophageal impedance with pH monitoring. Commonly, doubling the PPI dose or switching to another PPI will be pursued by the treating physician. Failure of such a therapeutic strategy may result in the addition of a transient lower oesophageal sphincter reducer or pain modulator. Anti-reflux surgery may be suitable for a subset of carefully studied patients.
Rationing Resources While Improving Quality-Reply
Authors: David M. Eddy
Journal: JAMA (1995)

<h3>In Reply.</h3> —Dr Fisher misunderstood the guideline for contrast agents. It was actually designed by physicians (not managers), and it recommended HOCAs only for intravenous administration in low-risk patients. But Fisher's main point is that, whereas transfers within diseases are ethical, transfers across diseases are not. I do not understand the distinction. Whether transfers are made within or across diseases, in both cases some individuals will lose while others will gain, and whether the losses or gains are within the same disease seems immaterial. For example, a policy that Fisher endorsed of "restricting mammography to more appropriate ages" will deprive a 38-year-old woman of coverage. Why should the ethics of that policy depend on whether the saved resources are used to screen other women for breast cancer (a within-disease transfer) or for cervical cancer (an across-disease transfer)? The example Fisher used to illustrate his point—stereotactic biopsies—was actually a within-patient transfer.
Implantable Cardioverter-Defibrillator Patients Who Are Upgraded and Respond to Cardiac Resynchronization Therapy Have Less Ventricular Arrhythmias Compared With Nonresponders
Authors: Joep Thijssen, C. Jan Willem Borleffs, Victoria Delgado, Johannes B. van Rees, Eline A.Q. Mooyaart, Rutger J. van Bommel, Lieselot van Erven, Eric Boersma, Jeroen J. Bax, Martin J. Schalij
Journal: Journal of the American College of Cardiology (2011)
The rate of atherosclerosis change during treatment of hyperlipoproteinemia.
Authors: D H Blankenhorn, S H Brooks, R H Selzer, R Barndt
Journal: Circulation (1978)

The rate of change of femoral atherosclerosis has been determined in 25 treated hyperlipoproteinemic patients. There were 13 Type II patients and 12 Type IV patients. Serial angiograms had been performed at an interval averaging 13 months. Film densities were analyzed by digigal image processing to yield a computer estimate of atherosclerosis (CEA). Serial measurements of CEA on each patient were used to determine atherosclerosis percent change per month in that patient. CEA percent change per month was significantly correlated ;ith triglyceride and cholesterol level. Lower lipid levels were associated with more rapid regression. When hyperlipoproteinemic types were considered separately, significant single correlates were confined to Type IV. Triglyceride level and CEA/age significantly predicted atherosclerosis change rate and accounted for 72% of the variability observed in Type IV patients.
Any questions: Does laser treatment offer a permanent cure for facial hirsutism in women?
Authors: J. H Barth
Journal: BMJ (1997)

Some women have isolated thick hairs growing on their faces and these can be effectively treated by any technique that can destroy a hair follicle. The most common method is electrolysis, but any procedure that destroys the hair root under the surface of the skin would be effective. The scar that develops at the site is small and invisible. Laser therapy is effective at destroying …
Cardiomyocyte apoptosis is related to left ventricular dysfunction and remodelling in dilated cardiomyopathy, but is not affected by growth hormone treatment
Authors: Waltraut Ibe, Antti Saraste, Stephan Lindemann, Stephanie Bruder, Michael Buerke, Harald Darius, Kari Pulkki, Liisa‐Maria Voipio‐Pulkki
Journal: European Journal of Heart Failure (2006)
NOTES ON VIBRION SEPTIQUE
Authors: M. Robertson
Journal: BMJ (1918)

VIBRION SEPTIQUE.[ TER BiTm MAY 25, x9i8l I~~~~~~~~~~~~~~~~~MNDJCA JOUUN& 583 been found sequestered in the partially destroyed carti- lages.Infected areas are met with here in close proximity to normal tissue, and more organisms have been found at the extreme limits of the affected and damaged areas than in the centre of fibrous degenerated tissue.One of the difficulties attendant on subsequent operations on joints, especially excision, is the secondary suppurations wlich undoubtedly arise from these loculi containing remnants of the original infection.Wound8 Entirely Healed but Breaking Down after a Long or Short Interval.
Informed Opinion on Informed Consent
Authors: Nicholas J. Demy
Journal: JAMA (1971)

<h3>To the Editor.—</h3> As a radiologist who has been sued, I have reflected earnestly on advice to obtain Informed Consent but have decided to "take the risks without informing the patient" and trust to "God, judge, and jury" rather than evade responsibility through a legal gimmick. I even thought of devising an Informed Consent for my type of practice along the lines of Burnham's (<i>Science</i><b>152</b>:448-449,1966) after a New York verdict affirmed a patient's right to be informed. Burnham's form for surgical patients differs a bit from Dr. Alfidi's (<b>216</b>:1325-1329, 1971), but has juicy possibilities. President Truman had a sign on his desk to remind him that "the buck stops here." So with the physician. He may not be God, judge, and jury, but he is their surrogate and must speak alone with the patient as Moses did with God on Mt. Sinai. Think what the Ten Commandments
Authors' reply to Rae and Marwick, Halpern, and Basak
Authors: G. Phoenix, S. Das, M. Joshi
Journal: BMJ (2012)

We agree that it is impractical to distinguish between streptococcal and staphylococcal cellulitis.1 As we said in our review,2 flucloxacillin should be used to cover both organisms or when the organism is unknown. However, when organisms are isolated, especially in community acquired meticillin resistant Staphylococcus aureus (CA-MRSA), antibiotic treatment may need to be tailored.

A clinical diagnosis for necrotising fasciitis is not always straightforward. In type B and type C infections (more insidious onset) magnetic resonance imaging can confirm or refute diagnosis, as well as demarcate the extent of disease. …
Beta blockers and loss of hearing.
Authors: R Faldt, H Liedholm, J Aursnes
Journal: BMJ (1984)

Loss of hearing in a 43 year old man during treatment with metoprolol was dose related and disappeared within a few months after the drug had been stopped. The hearing impairment was of mixed type, with an air bone gap without any disorder of the middle ear observable by conventional clinical methods. Similar scattered reports from international sources on loss of hearing during treatment with beta blockers are also presented.
A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis
Authors: Chiea C Khor, Stephen J Chapman, Fredrik O Vannberg, Aisling Dunne, Caroline Murphy, Edmund Y Ling, Angela J Frodsham, Andrew J Walley, Otto Kyrieleis, Amir Khan, Christophe Aucan, Shelley Segal, Catrin E Moore, Kyle Knox, Sarah J Campbell, Christian Lienhardt, Anthony Scott, Peter Aaby, Oumou Y Sow, Robert T Grignani, Jackson Sillah, Giorgio Sirugo, Nobert Peshu, Thomas N Williams, Kathryn Maitland, Robert J O Davies, Dominic P Kwiatkowski, Nicholas P Day, Djamel Yala, Derrick W Crook, Kevin Marsh, James A Berkley, Luke A J O'Neill, Adrian V S Hill
Journal: Nature Genetics (2007)
Colistin Sulfate and Sodium Colistimethate
Authors: R. M. Gabrielson
Journal: JAMA (1970)

To the Editor.—  We wish only to call attention to one small error in an otherwise fine report. The statement by Hardy et al ( 212 :1345, 1970) is made that the infant received  sulfate 4 mg/day   There are two considerably different forms of the antibiotic colistin available. First is colistin sulfate which is essentially the sulfate salt of the colistin base. Second is the methane sulfonate derivative of this base, namely, colistimethate sodium. The former product is referred to as Coly-Mycin S Oral Suspension and is used only for the treatment of enteric infections. Because of its toxicity, it is never administered intramuscularly. The second product is referred to as Coly-Mycin M Intramuscular (Injectable) which has a considerably lesser toxicity and is the form generally used for intramuscular systemic therapy.  Admittedly, the similarity of the names for both forms of this antibiotic leads easily to confusion but, in
Effect of new AIDS case definition on numbers of cases among homosexual and bisexual men in San Francisco
Authors: H. W. Sheppard
Journal: JAMA (1991)

ABSTRACT To the Editor. —On January 1,1992, the Centers for Disease Control (CDC) is expected to propose that a CD4+ T-lymphocyte cell count of 200 × 106 cells/L or less in a person seropositive for the human immunodeficiency virus (HIV), in the absence of other clinical findings, be added to the list of the acquired immunodeficiency syndrome (AIDS) defining conditions. Some of the consequences of this action can be estimated from data collected in the San Francisco (Calif) Men's Health Study and the San Francisco General Hospital Cohort. These cohorts comprise approximately 1250 homosexual and bisexual men recruited in 1983 and 1984 by a combination of sampling and volunteer procedures. Both cohorts have been examined regularly since recruitment and CD4+ T-lymphocyte counts have been determined at each examination.By the end of 1990,271 cases of AIDS meeting the 1987 criteria defined by the CDC had been diagnosed. If the proposed
Intermediate care offers no "quick fix" solution
Authors: K. Inman
Journal: BMJ (2002)

Government plans to prevent unnecessary hospital admissions and help vulnerable patients live more independently are in grave danger of failing, a conference in London heard this week.

Andrew Dearden, chairman of the BMA's community care committee, said the government was relying on a steady supply of private beds and facilities to support its plans for intermediate care. “But it has failed to prevent the massive loss of nursing home beds and facilities, which now threatens the whole strategy,” he said.

Intermediate care was often cited as the solution to some intractable NHS problems, including delayed discharge, said Dr Dearden. “Yet one third of the £150m ($213m; €242m) announced by the …
Action of dopamine on the human iris
Authors: A. S. D. Spiers, D. B. Calne
Journal: BMJ (1969)

Dopamine eye drops produce marked dilatation of the pupil in man. This mydriatic effect is inhibited by pretreatment with guanethidine. It is therefore concluded that dopamine acts indirectly via adrenergic nerve endings, rather than exerting a direct effect on adrenergic receptors in the dilator pupillae muscle. In this respect dopamine resembles the phenyl-alkylamines, such as tyramine, rather than the catecholamines, adrenaline and noradrenaline. If dopamine acts by releasing noradrenaline from adrenergic nerve endings, high concentrations of dopamine could lead to depletion of noradrenaline stores, since synthesis might be unable to keep pace with release. This could be the explantion for the orthostatic hypotension found in patients taking L-dopa for Parkinsonism.
Provoking Variant Angina
Authors: Rex Mac Alpin
Journal: New England Journal of Medicine (1976)

Prinzmetal's variant angina pectoris is a clinical syndrome characterized by recurrent attacks of anginal discomfort at rest associated with transient ST-segment elevation in the electrocardiogram. Attacks are rarely provoked by stress, and exercise capacity is paradoxically well preserved. Although moderately severe fixed anatomic narrowing is commonly observed in the coronary artery supplying the region of the heart showing ST-segment elevation during attacks, the degree of obstruction seen between attacks is insufficient to account for the attack,1 and frequently there is no organic coronary-artery stenosis at all.2 Since the report of Dhurandhar et al.3 and that of Oliva et al. in . . .
Screening for Chlamydia — A Key to the Prevention of Pelvic Inflammatory Disease
Authors: Susan D. Hillis, Judith N. Wasserheit
Journal: New England Journal of Medicine (1996)

Pelvic inflammatory disease and its severe, costly consequences are preventable. “Pelvic inflammatory disease” refers to infection of the endometrium, fallopian tubes, and contiguous structures. Although it is often caused by multiple infectious organisms, pelvic inflammatory disease results most frequently from the ascent of sexually transmitted chlamydial or gonococcal infection from the cervix into the upper genital tract.1 More than 10 percent of women of reproductive age report a history of such disease,2 and it develops in more than 1 million American women annually.1 In 1994, the estimated costs associated with symptomatic pelvic inflammatory disease exceeded $5.5 billion.1,3 However, published . . .
Intra-Uterine Therapeutics
Authors: T. M. Madden
Journal: BMJ (1884)

tion ; but, in the autumn of ISS2, the intervals between the periods became so short, that she was only free from the discharge for three or four days, sometimes, indeed, lor hardly a day during the entire month.In April, 1883, her nmedical attendant dilated the uterus, and, not discovering aniy intra-uterine growth, uise(d the curette, and applied nitric acid to the cavity of the uterus.After this, she was bettor for a short time, but speeaily relapsed into her former condition.On coming under my care, early in February last, she stated that, for the previous six moniths, she hadl never been free for even a single day from a h.iinorrhagic discharge; while, at intervals of about eighteen days, at dates correspon ling, as she supposed, to the recur- rence of thc miienistrual periods, the h-winorrhage became alarming.On examiniing ler, I found the Uterus to be-large.Tlle soundpenetrated to the dcpth of more than four inelhes, and its withdrawal was followedl by sharp bleeding.I wishe(d to dilate the uterus, andl again to explore the cavity, but the patient objectedl so strongrly that I resolved to try the effect of injecting the iodised plhenlol, and onl February 16th injected a drachbn.This (litl not cauise any pain, nor did aniy of the fluid return, thus showing that the cavity of ti e uterus was large, but it only checked the bleeding for one day; the second( injection, made after the lapse of a week, had somewhat better effect, btut the bleeding returned in twvo days.Fr om Februiary 23rd to April 18th 1 injected the phenol twice a week, with the most satisfactory results.After the fourth injection, the luvmorrhage entirely ceased and shortly after this the fluid injected began to flow back into the speculum aLs soon as the tube of tlle syringe was withdrawn, proving that the cavity had contracted considerably for some time after April 18th.I swabbedl out the uterus once a week with the plhenol, carried up on a probe in the usual manner.The patient is now perfectly well.Lastly, I may state that I have on several occasions treated cases of heemorrhage depending on the presence of submucous and intramural fibroids, by the injection of the iodised phenol, with most satisfactory results.
India remains on US trade "priority watch list" for failing to uphold international drug company patents
Authors: S. Arie
Journal: BMJ (2013)

The US government has said that it is seriously concerned about recent rulings in India on drug patenting that have favoured the country’s generics industry over international drug companies.

In its annual report on intellectual property protection by trading partners, the Office of the US Trade Representative has kept India on its “priority watch list,” citing recent decisions by Indian courts to deny international companies exclusive rights over anticancer drugs that they had developed. The report also said that India had made limited progress in 2012 in improving its weak legal framework on intellectual property rights and the enforcement system.1

Earlier this year India’s Supreme Court ruled that the Swiss company Novartis was not entitled to a patent on its drug imatinib mesilate (which …