tbuckley/cabot-search huggingface dataset:
Reversal of Ethinyl Estradiol-induced Bile Secretory Failure with Triton WR-1339
Authors: Francis R. Simon, Manuel Gonzalez, Eileen Sutherland, Luigi Accatino, Roger A. Davis
Journal: Journal of Clinical Investigation (1980)

The effects of Triton WR-1339 and phenobarbital on ethinyl estradiol bile secretory failure were examined to determine the mechanism responsible for decreased bile salt excretion. When administered to ethinyl estradiol-treated rats, Triton WR-1339 restored bile salt independent bile flow and maximum taurocholate transport, whereas phenobarbital corrected bile flow only. Ethinyl estradiol decreased the activities of Na+-K+-ATPase, 5′-nucleotidase, while increasing the activities of Mg++-ATPase and alkaline phosphatase. In contrast to these heterogeneous changes in surface membrane enzyme activities, the number and affinity of [14C]cholic acid carriers were not altered. When administered in vivo or added directly to surface membrane fractions Triton WR-1339 restored the activities of Na+-K+-ATPase and Mg++-ATPase of rats treated with ethinyl estradiol through a process that did not require protein synthesis (unaffected by cycloheximide). Phenobarbital also restored the activity of Na+-K+-ATPase to control levels, but, unlike Triton WR-1339 it did not correct the defect responsible for reduced bile salt secretion. Ethinyl estradiol increased the concentration of cholesterol esters in surface membrane fractions. When administered to ethinyl estradiol-treated rats, Triton WR-1339 restored cholesterol ester concentrations to normal, whereas phenobarbital did not. These combined data suggest that decreased or altered bile salt carriers or reduced sodium driving forces resulting from impaired activity of Na+-K+-ATPase are not responsible for decreased bile salt excretion in ethinyl estradiol-treated rats. It is proposed that the diverse changes in surface membrane function, which are associated with ethinyl estradiol bile secretory failure, may be the result of a generalized alteration in membrane lipid structure.
Ductular morphogenesis and functional polarization of normal human biliary epithelial cells in three-dimensional culture
Authors: Yuichi Ishida, Sharon Smith, Lorraine Wallace, Takaharu Sadamoto, Masashi Okamoto, Marcus Auth, Mario Strazzabosco, Luca Fabris, Juan Medina, Jesús Prieto, Alastair Strain, James Neuberger, Ruth Joplin
Journal: Journal of Hepatology (2001)
Abstract 4850: Tumor mitochondria contribute to autophagic properties of the cancer cells
Authors: Yi-Fang Tu, Yewei Ma, Lee-Jun C. Wong
Journal: Cancer Research (2010)

Abstract Autophagy is a cellular housekeeping process that removes damaged or unwanted cellular components and recycles them to build new constituents. It is essential for tumor growth under adverse environment. Mitochondria play an important role in the formation of autophagosome and its subsequent docking and fusion with lysosome. In order to study the contribution of mitochondria to the regulation of homeostatic autophagy in cancer cells, we used a transmitochondrial cytoplasmic hybrid (cybrid) system to investigate the role of tumor-derived mitochondria in a defined nuclear background. Since LC3-II is the autophagosomal membrane-bound form of microtubule-associated protein 1 light chain 3 (LC3-I), increased LC3-II or increased LC3-II/LC3-I ratio is an indication of activation of autophagy. Cybrids containing mitochondria derived from a highly metastatic breast cancer cell line MDA-MB-231 (c231) exhibited lower LC-II levels but higher ratio of LC3-II/LC-I than other cybrids containing mitochondria derived from low or moderate metastatic breast cancer cell lines MDA-MB-436 and MDA-MB-468, as well as mammary epithelial cell MCF-10A (c10A). Increase of LC3 puncta on immunofluorescence stain and decrease of sequestosome 1 (p62/SQSTM1), a marker of autophagic flux, in c231 cells, compared to other cybrids, further indicated that mitochondria derived from high metastatic breast cancer cell line MDA-MB-231 could increase autophagy and accelerate autophagic flux. The accelerated autophagic flux in c231 cells can be blocked by the autophagy inhibitor bafilomycin-A1. In addition, the mitochondria in c231 cells were noted to promote mitochondrial permeability transition (MPT) and were surrounded by LC3 puncta. These results suggested that tumor mitochondria from highly metastatic breast cancer cell line, MDA-MB-231, can promote homeostatic autophagy of cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4850.
The Relative Impact of Smoking and Oral Contraceptive Use on Women in the United States
Authors: Gary M. Goldbaum
Journal: JAMA (1987)

Women who smoke and use oral contraceptives (OCs) are at increased risk for cardiovascular and cerebrovascular disease. To study the prevalence of smoking and OC use and other behaviors affecting health, 28 states and the District of Columbia conducted telephone surveys during 1981 through 1983. More than 22,000 US adults were interviewed, of whom 5779 women aged 18 to 44 years were studied. Data were weighted to represent the US population. Overall, 7.4% of US women aged 18 to 44 years reported smoking and using OCs; 1.1% reported smoking 25 or more cigarettes per day while using OCs. Although women aged 18 to 24 years were most likely to smoke and use OCs, combined smoking and OC use contributed substantially to the number of excess cases of myocardial infarctions occurring among US women aged 35 to 44 years. However, regardless of OC use, smoking accounted for most of the excess cases. Therefore, health care providers need to intensify their efforts to reduce smoking among their patients.
The Effect of Propranolol on Portal Hypertension in Patients with Cirrhosis: A Hemodynamic Study
Authors: Didier Lebrec, Patrick Hillon, Cristina MuńOz, Gerard Goldfarb, Olivier Nouel, Jean-Pierre Benhamou
Journal: Hepatology (1982)

The gradient between wedged and free hepatic venous pressures was measured in patients with alcoholic cirrhosis before and 1, 3, and 9 months after continuous oral administration of propranolol at doses reducing the heart rate by 25% or after administration of a placebo. The gradient between wedged and free hepatic venous pressures decreased throughout the duration of propranolol administration, and it did not significantly change in the patients receiving placebo. Since the gradient between wedged and free hepatic venous pressures closely reflects portal venous pressure in alcoholic cirrhosis, it is concluded that continuous oral administration of propranolol produced sustained reduction in portal venous pressure in these patients.
Can students learn clinical method in general practice? A randomised crossover trial based on objective structured clinical examinations
Authors: E. Murray, B. Jolly, M. Modell
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To determine whether students acquired clinical skills as well in general practice as in hospital and whether there was any difference in the acquisition of specific skills in the two environments. <b>Design:</b> Randomised crossover trial. <b>Subjects and setting:</b> Annual intake of first year clinical students at one medical school. <b>Intervention:</b> A 10 week block of general internal medicine, one half taught in general practice, the other in hospital. Students started at random in one location and crossed over after five weeks. <b>Outcome measures:</b> Students9 performance in two equivalent nine station objective structured clinical examinations administered at the mid and end points of the block: a direct comparison of the two groups9 performance at five weeks; analysis of covariance, using their first examination scores as a covariate, to determine students9 relative improvement over the second five weeks of their attachment. <b>Results:</b> 225 students rotated through the block; all took at least one examination and 208 (92%) took both. For the first half of the year there was no significant difference in the students9 acquisition of clinical skills in the two environments; later, however, students taught in general practice improved slightly more than those taught in hospital (P=0.007). <b>Conclusions:</b> Students can learn clinical skills as well in general practice as in hospital; more work is needed to clarify where specific skills, knowledge, and attitudes are best learnt to allow rational planning of the undergraduate curriculum.
285 The impact of hcv core protein-related cell cycle modulation on hepatic regeneration and inflammation - an in vivo study based on conditional HCV core transgenics
Authors: M.L. Chang, C.T. Yeh, I.S. Sheen, D.I. Tai, S.M. Lin, J.C. Chen, C.T. Chiu, D.Y. Lin
Journal: Journal of Hepatology (2006)
History of diaphragm physiology: the achievements of Galen
Authors: JP Derenne, A Debru, AE Grassino, WA Whitelaw
Journal: European Respiratory Journal (1995)

Galen (129-200 AD) produced a large written output which was to remain one of the major basis of clinical medicine for centuries. His contribution to respiration, reported in his own books and in those of Oribasius, was that of a chest physician and of an experimental physiologist. He described in minute details how to perform a remarkable series of experiments by which he demonstrated the anatomy and function of the respiratory muscles. He described the actions of the diaphragm and how it moves the rib cage, in a series of spinal chord sections and muscle denervations. He investigated the passive or active nature of expiration and made fine observations of lung movements through the exposed pleural space. He described the interaction between the lungs and chest wall and developed the concept of interaction between ribcage and abdominal muscles in maintaining the position of the diaphragm, showing a clear understanding of the principle that the diaphragm can move upward during an isovolume manoeuvre as long as the ribcage is allowed to expand. A skillful clinician, Galen applied his theories of the analysis of problems at the bedside, particularly in patients affected with dyspnoea which he attributed to respiratory muscle dysfunction.
The Autopsy and Asbestos Exposure
Authors: Jean Spencer Felton
Journal: JAMA (1980)

<h3>To the Editor.—</h3> In the article entitled "The Autopsy: Past, Present, and Future" by Anderson and co-workers (242:1056, 1979), the fall in the rate of autopsies is decried, and several cogent reasons are presented for a return to the previous high number of such examinations, a goal formerly pursued by dedicated house officers. One additional need for postmortem reviews has been given emphasis in recent years by the epidemiologic and clinical information gathered in connection with the asbestos-related disease. Because workers are now beginning to present radiological and altered physiological evidence of the effects of the inhalation of free asbestos fiber, years to decades after initial work exposure, a problem in worker's compensation adjudication has arisen. The changes elicited through clinical study, although present, most often do not have accompanying symptoms,<i>as yet</i>, nor have they caused any disability,<i>as yet</i>. There will be disability, however, with the passing of time.
TH-302 in Combination with Radiotherapy Enhances the Therapeutic Outcome and Is Associated with Pretreatment [18F]HX4 Hypoxia PET Imaging
Authors: Sarah G.J.A. Peeters, Catharina M.L. Zegers, Rianne Biemans, Natasja G. Lieuwes, Ruud G.P.M. van Stiphout, Ala Yaromina, Jessica D. Sun, Charles P. Hart, Albert D. Windhorst, Wouter van Elmpt, Ludwig J. Dubois, Philippe Lambin
Journal: Clinical Cancer Research (2015)

Conventional anticancer treatments are often impaired by the presence of hypoxia. TH-302 selectively targets hypoxic tumor regions, where it is converted into a cytotoxic agent. This study assessed the efficacy of the combination treatment of TH-302 and radiotherapy in two preclinical tumor models. The effect of oxygen modification on the combination treatment was evaluated and the effect of TH-302 on the hypoxic fraction (HF) was monitored using [(18)F]HX4-PET imaging and pimonidazole IHC stainings.Rhabdomyosarcoma R1 and H460 NSCLC tumor-bearing animals were treated with TH-302 and radiotherapy (8 Gy, single dose). The tumor oxygenation status was altered by exposing animals to carbogen (95% oxygen) and nicotinamide, 21% or 7% oxygen breathing during the course of the treatment. Tumor growth and treatment toxicity were monitored until the tumor reached four times its start volume (T4×SV).Both tumor models showed a growth delay after TH-302 treatment, which further increased when combined with radiotherapy (enhancement ratio rhabdomyosarcoma 1.23; H460 1.49). TH-302 decreases the HF in both models, consistent with its hypoxia-targeting mechanism of action. Treatment efficacy was dependent on tumor oxygenation; increasing the tumor oxygen status abolished the effect of TH-302, whereas enhancing the HF enlarged TH-302's therapeutic effect. An association was observed in rhabdomyosarcoma tumors between the pretreatment HF as measured by [(18)F]HX4-PET imaging and the T4×SV.The combination of TH-302 and radiotherapy is promising and warrants clinical testing, preferably guided by the companion biomarker [(18)F]HX4 hypoxia PET imaging for patient selection.
Changes in Renal Blood Flow and Possibly the Intrarenal Distribution of Blood during the Natriuresis Accompanying Saline Loading in the Dog*
Authors: Laurence E. Earley, Robert M. Friedler
Journal: Journal of Clinical Investigation (1965)

Sodium excretion during extracellular volume expansion and associated changes in renal blood flow and intrarenal blood distribution during natriuresis accompanying saline loading in dogs
In vitro, ex vivo, in vivo veritas
Authors: L. Borgström
Journal: Allergy (1999)

In vitro assessments of inhaler performance are important in product development and quality control, but are not, as such, good predictors of performance in vivo . It is, however, possible to modify in vitro techniques so that they more closely resemble the in vivo situation. Measurements of fine‐particle dose (defined as the amount of drug with an aerodynamic diameter less than 5 μm) by cascade impactor have shown that the measured fine‐particle dose in vitro is highly dependent on the geometry of the inlet to the impactor, the fine‐particle dose being considerably lower when the cast of a human throat (an “anatomical throat”) is used than when a standard glass inlet is used. This difference is, however, less with a dry‐powder inhaler such as Turbuhaler® than with a pressurized metered‐dose inhaler (pMDI). Furthermore, there is a good correlation between fine‐particle dose measured in vitro and in vivo lung deposition, provided that an anatomically correct inlet is used for the in vitro determination. Studies in children have shown that the degree of lung deposition of budesonide, delivered via Turbuhaler, is of the same order of size as the in vitro fine‐particle dose. No comparable data are available for pMDIs; however, since children are smaller than adults, it is likely that differences in lung deposition between Turbuhaler and pMDIs are probably greater in children than in adults.
Only the mother of all reorganisations can save the NHS
Authors: B. Morley
Journal: BMJ (2015)

“No more top-down reorganisations” is a familiar mantra. Sorry, folks, but the NHS has been reduced to such a state that only the mother of all reorganisations can now save it.

After three decades of wanton destruction, from Margaret Thatcher’s Griffiths report on NHS management in 1983, through to her internal market measures, then New Labour’s initiation of the competition and privatisation agenda, and finally Andrew Lansley’s cataclysmic Health and Social Care Act 2012 and its fallout, only radical measures can now save and restore the modern wonder of the world back to its rightful place.

If I ruled the NHS I …
Drug Warnings That Can Cause Fits — Communicating Risks in a Data-Poor Environment
Authors: Jerry Avorn
Journal: New England Journal of Medicine (2008)

In 2005, after receiving case reports of suicides by patients taking anticonvulsant medications, the Food and Drug Administration (FDA) asked the manufacturers of 11 drugs in this class to report all suicide-related events in the controlled trials they had conducted over many years. This past January, nearly 3 years later, the agency completed its analysis of these data and announced that it had found a near-doubling of suicidal ideation and behavior among trial subjects randomly assigned to receive these drugs rather than placebo1 (odds ratio, 1.8; 95% confidence interval [CI], 1.2 to 2.72). For patients in epilepsy studies, the . . .
The Lister Memorial
Authors: W. W. Keen
Journal: JAMA (1913)

article very carefully, for I state that two weeks after the removal of the lip, I do a radical dissection of the cervical lymph-nodes including the submental and submaxillary.At the second operation the facial arteries are cut; but as the flaps are now healed in place their preservation is no longer necessary.To save space I referred to a previous article in which I advo- cated a very thorough neck dissection in these cases, and as I do not like to have such an extensive wound in continuity with the mouth, I do a two-step operation.I also remove the lip wide of the growth, and my operation permits this by allowing full use, without tension, of the loose skin of the neck.In Dr. Stewart's original article he states that there is sometimes "an offensive suppuration" following his operation; such suppura- tion is, in my experience, often accompanied by sloughing in the wound.Dr. Stewart misunderstood in thinking that I stated that sloughing of the Hap occurs in his operation, for C have not known this to happen, Ii is certainly remarkable,
Learning to let go of our organs
Authors: D. Roskell
Journal: BMJ (2001)

We don't need to live next to a faulty crematorium to inhale bits of dead people. On an atomic level, every breath we take contains stuff that was once someone else.

So what claim do we have, during the period between death and atomic recycling, on the physical material that used to be ours?

For those who believe in literal resurrection of the body the claim is total. The body must be buried complete or it won't work properly next time. But few truly believe this. Even the ancient Egyptians preserved the body's external appearance while removing organs and replacing them with sand and cloth. Throughout history the emphasis has been on preserving appearance, leaving the messy inner details to the gods.

> The body and its components have gained the holy quality previously reserved for relics 

So why should most of us care what happens to our livers when we've finished with them? Mine can go to the worms, or preferably to one of my desperately ill fellow humans who needs a transplant. My friends can say goodbye to the …
Anti-Ischemic Effect of a Novel Cardioprotective Agent, JTV519, Is Mediated Through Specific Activation of δ-Isoform of Protein Kinase C in Rat Ventricular Myocardium
Authors: Koichi Inagaki, Yasuki Kihara, Wataru Hayashida, Toshiaki Izumi, Yoshitaka Iwanaga, Takeshi Yoneda, Yuzo Takeuchi, Katsuo Suyama, Eri Muso, Shigetake Sasayama
Journal: Circulation (2000)

Background —A new 1,4-benzothiazepine derivative, JTV519, has a strong protective effect against Ca 2+ overload–induced myocardial injury. We investigated the effect of JTV519 on ischemia/reperfusion injury in isolated rat hearts. Methods and Results —At 30 minutes of reperfusion after 30-minute global ischemia, the percent recovery of left ventricular developed pressure was improved, and the creatine phosphokinase and lactate dehydrogenase leakage was reduced in a concentration-dependent manner when JTV519 was administered in the coronary perfusate both at 5 minutes before the induction of ischemia and at the time of reperfusion. The myocardial protective effect of JTV519 was completely blocked by pretreatment of the heart with GF109203X, a specific protein kinase C (PKC) inhibitor. In contrast, the effect of JTV519 was not affected by α 1 -, A 1 -, and B 2 -receptor blockers that couple with PKC in the cardiomyocyte. Both immunofluorescence images and immunoblots of JTV519-treated left ventricular myocardium and isolated ventricular myocytes demonstrated that this agent induced concentration-dependent translocation of the δ-isoform but not the other isoforms of PKC to the plasma membrane. Conclusions —The mechanism of cardioprotection by JTV519 against ischemia/reperfusion injury involves isozyme-specific PKC activation through a receptor-independent mechanism. This agent may provide a novel pharmacological approach for the treatment of patients with acute coronary diseases via a subcellular mechanism mimicking ischemic preconditioning.
The Lymphoscintigraphic Evaluation of Patients with Klippel-Trenaunay Syndrome
Authors: R P DU CRET, B C AAFEDT, P J WYMORE, R J BOUDREAU, C C KUNI
Journal: Clinical Nuclear Medicine (1993)

Lymphoscintigraphy performed with Tc-99m-labeled antimony sulfur colloid is useful in the selection of patients for vascular microsurgery. Klippel-Trenaunay syndrome is characterized by multiple hemangiomata, limb hypertrophy, and vascular and lymphatic abnormalities. Lymphoscintigraphic findings in this syndrome are demonstrated.
Prospects for Research in Diabetes Mellitus
Authors: Jerrold M. Olefsky
Journal: JAMA (2001)

Diabetes mellitus is the sixth leading cause of death in the United States, and morbidities resulting from diabetes-related complications such as retinopathy, kidney disease, and limb amputation cause a huge burden to the national health care system. Identification of the genetic components of type 1 and type 2 diabetes is the most important area of research because elucidation of the diabetes genes will influence all efforts toward a mechanistic understanding of the disease, its complications, and its treatment, cure, and prevention. Also, the link between obesity and type 2 diabetes mandates a redoubled effort to understand the genetic and behavioral contributions to obesity.
Targeting Prostate Cancer with Conditionally Replicative Adenovirus Using PSMA Enhancer
Authors: Sang-Jin Lee, Yanping Zhang, Sang Don Lee, Chaeyong Jung, Xiong Li, Hong-Sup Kim, Kyung-Hee Bae, Meei-Huey Jeng, Chinghai Kao, Thomas Gardner
Journal: Molecular Therapy (2004)

Prostate cancer is the second most commonly diagnosed cancer in men and accounts for significant mortality and morbidity in the United States. Initially androgen-dependent, prostate cancer ultimately becomes androgen-independent, which makes the disease extremely difficult to cure. In this study, we examined the use of conditionally replication-competent adenovirus for the treatment of hormone-independent prostate cancer. We utilized PSME, an enhancer element for prostate-specific PSMA expression, to control viral E1A protein expression and achieve exclusive virus replication in prostate. Western blotting confirmed that PSME mediated high E1A protein expression in PSMA-positive, androgen-independent prostate cancer cells (C4-2 and CWR22rv), but was much less active in PSMA-negative cancer cells (PC-3 and A549). Consistent with E1A protein expression, the recombinant adenovirus Ad5-PSME-E1a replicated in C4-2 and CWR22rv almost as efficiently as wild type with low levels of androgen, but its replication was significantly attenuated in PSMA-negative cells. In the in vitro killing assay, Ad5-PSME-E1a lysed all C4-2 and CWR22rv cells 5 days after infection, with minimal effect on PSMA-negative cells. In addition, injections of 1.7 x 10(8) plaque-forming units in a CWR22rv xenograft model in nude mice induced significant tumor growth delay, with a substantial necrotic area. These studies suggest that PSME-driven replication-competent adenovirus may be a new therapeutic modality for prostate cancer patients after hormone ablation therapy.