tbuckley/cabot-search huggingface dataset:
RNA Interference Reveals that Ligand-Independent Met Activity Is Required for Tumor Cell Signaling and Survival
Authors: Nariyoshi Shinomiya, Chong Feng Gao, Qian Xie, Margaret Gustafson, David J. Waters, Yu-Wen Zhang, George F. Vande Woude
Journal: Cancer Research (2004)

Abstract Hepatocyte growth factor/scatter factor-Met signaling has been implicated in tumor growth, invasion, and metastasis. Suppression of this signaling pathway by targeting the Met protein tyrosine kinase may be an ideal strategy for suppressing malignant tumor growth. Using RNA interference technology and adenovirus vectors carrying small-interfering RNA constructs (Ad Met small-interfering RNA) directed against mouse, canine, and human Met, we can knock down c-met mRNA. We show a dramatic dependence on Met in both ligand-dependent and ligand-independent mouse, canine, and human tumor cell lines. Mouse mammary tumor (DA3) cells and Met-transformed NIH3T3 (M114) cells, as well as both human and canine prostate cancer (PC-3 and TR6LM, human sarcoma (SK-LMS-1), glioblastoma (DBTRG), and gastric cancer (MKN45) cells, all display a dramatic reduction of Met expression after infection with Ad Met small-interfering RNA. In these cells, we observe suppression of tumor cell growth and viability in vitro as well as inhibition of hepatocyte growth factor/scatter factor-mediated scattering and invasion in vitro, whether Met activation was ligand dependent or not. Importantly, Ad Met small-interfering RNA led to apoptotic cell death in many of the tumor cell lines, especially DA3 and MKN45, but did not adversely affect MDCK canine kidney cells. Met small-interfering RNA also abrogated downstream Met signaling to molecules such as Akt and p44/42 mitogen-activated protein kinase. We further show that intratumoral infection with c-met small-interfering RNA adenovirus results in a substantial reduction in tumor growth. Thus, Met small-interfering RNA adenoviruses are reliable tools for studying Met function and raise the possibility of their application for cancer therapy.
Abstract 5159: Kruppel-like factor 9 modulates the growth and differentiation of glioblastoma-derived neoplastic stem cells
Authors: Mingyao Ying, Shuli Xia, John Laterra
Journal: Cancer Research (2010)

Abstract Glioblastoma (GBM) is the most prevalent brain tumor with high frequency of recurrence. During the past decade, the identification of neoplastic stem-like cells in diverse human cancers including GBM represents an important conceptual advance in cancer biology and suggests new therapeutic strategies. We found that retinoic acid (RA) induces growth arrest and cell differentiation of GBM-derived stem-like cells (GBM-SCs). RA treatment also inhibited the growth of GBM-SC xenografts in mice. We studied gene expression changes during RA-induced GBM-SC differentiation and found that kruppel-like factor 9 (KLF9) expression increased 8-fold after RA treatment. KLF proteins are evolutionarily conserved zinc finger-containing transcription factors that bind to GC-rich DNA regions. KLF9 is known to function as a progesterone receptor cofactor to regulate progesterone-responsive genes but its function in cancer and stem cell biology is essentially unknown. We used lentivirus-based methods to modulate KLF9 expression in GBM-SCs. KLF9 gain-of-function induced GBM-SC differentiation and inhibited GBM-derived neurosphere formation in clonogenic and neurosphere cell growth assays. KLF9 gain-of-function also prevented the growth of GBM-SC subcutaneous xenografts in mice. Knockdown of KLF9 suppressed RA-induced differentiation of GBM-SCs. These data indicate that KLF9 and possibly other KLF family members modulate transcriptional mechanisms that regulate GBM-SC growth, differentiation, and possibly tumor initiation. Currently, we are utilizing gene expression microarray and chromatin immunoprecipitation assays to study the KLF9 target genes. Our findings provide new insights pertaining to the molecular regulation of the GBM-SC phenotype and could lead to innovative therapeutic strategies for targeting the stem-like cell pool in malignant brain tumors. 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 5159.
Use of Cytomegalovirus Immune Globulin to Prevent Cytomegalovirus Disease in Renal-Transplant Recipients
Authors: D R Snydman, B G Werner, B Heinze-Lacey, V P Berardi, N L Tilney, R L Kirkman, E L Milford, S I Cho, H L Bush, A S Levey
Journal: New England Journal of Medicine (1987)

We undertook a prospective randomized trial to examine whether an intravenous cytomegalovirus (CMV) immune globulin would prevent primary CMV disease in renal-transplant recipients. Fifty-nine CMV-seronegative patients who received kidneys from donors who had antibodies against CMV were assigned to receive either intravenous CMV immune globulin or no treatment. The immune globulin was administered in multiple doses over the first four months after transplantation. The incidence of virologically confirmed CMV-associated syndromes was reduced from 60 percent in controls to 21 percent in recipients of CMV immune globulin (P less than 0.01). Fungal or parasitic superinfections were not seen in globulin recipients but occurred in 20 percent of controls (P = 0.05). Only 4 percent of globulin recipients had marked leukopenia (reflecting serious CMV disease), as compared with 37 percent of the controls (P less than 0.01). There was a concomitant but not statistically significant reduction in the incidence of CMV pneumonia (17 percent of controls as compared with 4 percent of globulin recipients). A significant reduction in serious CMV-associated disease was observed even when patients were stratified according to therapy for transplant rejection (P = 0.04). We observed no effect of immune globulin on rates of viral isolation or seroconversion, suggesting that treated patients often harbored the virus but that clinically evident disease was much less likely to develop in them. We conclude that CMV immune globulin provides effective prophylaxis in renal-transplant recipients at risk for primary CMV disease.
A docetaxel-carboxymethylcellulose nanoparticle outperforms the approved taxane nanoformulation, Abraxane, in mouse tumor models with significant control of metastases
Authors: Mark J. Ernsting, Mami Murakami, Elijus Undzys, Ahmed Aman, Barry Press, Shyh-Dar Li
Journal: Journal of Controlled Release (2012)
Exercise capacity is related to echocardiographic indexes of diastolic function in patients with hypertrophic cardiomyopathy
Authors: C. Briguori, S. Botocchi, M. Romano, F. Manganelli, M.Angela Losi, R. Gottilla, Q. Ciampi, M. Condorelli, M. Chiariello
Journal: Journal of the American College of Cardiology (1998)
Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate
Authors: Ho Jung Shin, Naohiko Anzai, Atsushi Enomoto, Xin He, Do Kyung Kim, Hitoshi Endou, Yoshikatsu Kanai
Journal: Hepatology (2007)

The liver plays an important role in the elimination of endogenous and exogenous lipophilic organic compounds from the body, which is mediated by various carrier proteins that differ in substrate specificity and kinetic properties. Here, we have characterized a novel member of the organic anion transporter family (SLC22) isolated from human liver. The transporter named organic anion transporter 7 (OAT7/ SLC22A9) showed 35% to 46% identities to those of other organic anion transporters of SLC22 family. When expressed in Xenopus oocytes, OAT7 mediated Na+-independent, high-affinity transport of sulfate-conjugated steroids, estrone sulfate (ES; Km = 8.7 μM), and dehydroepiandrosterone sulfate (Km = 2.2 μM). In addition, OAT7 interacted with negatively charged sulfobromophthalein, indocyanine green, and several sulfate-conjugated xenobiotics. In contrast, glucuronide and glutathione conjugates exhibited no inhibitory effects on OAT7-mediated [3H]ES transport. OAT7-mediated [3H]ES transport was trans-stimulated by three-carbon to five-carbon (C3 to C5) short-chain fatty acids. The efflux of [14C]butyrate (C4) via OAT7 was significantly trans-stimulated by extracellular ES. Furthermore, OAT7 mediated [14C]butyrate uptake and [3H]ES efflux in exchange for extracellular butyrate both in Xenopus oocytes and OAT7-stably expressing cells. OAT7 protein was localized in the sinusoidal membrane of hepatocytes by immunohistochemical analysis. Conclusion: OAT7 is the first liver-specific transporter among members of the organic anion transporters of SLC22 family. Our findings suggest a new class of substrates for organic anion transporters and provide evidence for the transport of anionic substances such as sulfate-conjugates in exchange for butyrate in hepatocytes. (HEPATOLOGY 2007;45:1046–1055.)
Acute hemodynamic effects of captopril in children with a congestive or restrictive cardiomyopathy.
Authors: A R Bengur, R H Beekman, A P Rocchini, D C Crowley, M A Schork, A Rosenthal
Journal: Circulation (1991)

The acute hemodynamic effects of captopril were evaluated at cardiac catheterization in 16 children (age, 0.3-18 years) with cardiomyopathy. Twelve children had congestive cardiomyopathy, whereas four had restrictive cardiomyopathy. Hemodynamic measurements were obtained 30 and 60 minutes after the oral administration of captopril (0.5 mg/kg). Blood pressures were measured in the aorta, pulmonary artery, right atrium, and pulmonary capillary wedge position; cardiac outputs were measured by the thermodilution technique. Hemodynamic data could not be obtained after the administration of captopril in one child with congestive cardiomyopathy because of an immediate, severe hypotensive response. In 11 of 12 children with congestive cardiomyopathy, cardiac index increased by 22%, from 2.3 to 2.8 l/min/m2 (p less than 0.05), and stroke volume increased by 22%, from 23 to 28 ml/m2 (p less than 0.05). Systemic vascular resistance decreased from 32 to 21 units.m2 (p less than 0.01), but the mean aortic pressure did not change significantly. In contrast, four children with restrictive cardiomyopathy had no change in cardiac output after captopril, but there was a trend toward significant arterial hypotension (mean aortic pressure decreased from 78 to 59 mm Hg). Thus, captopril acutely reduced systemic vascular resistance and increased both cardiac output and stroke volume in children with congestive cardiomyopathy. In children with restrictive cardiomyopathy, however, captopril did not affect cardiac output, but it did decrease aortic pressure. These data indicate that captopril may benefit children with a congestive cardiomyopathy but that captopril probably should not be used in children with restrictive disease.
US surgeon who campaigned against potentially dangerous device receives legal threat
Authors: O. Dyer
Journal: BMJ (2014)

A former Harvard surgeon who led a successful campaign against power morcellators—surgical devices designed to chop up uterine fibroids for removal through laparoscopic incisions—has said that he will continue to fight against the procedure despite having received a threatening legal letter from the manufacturer of the device, which was used on his wife.

Hooman Noorchashm, a cardiothoracic surgeon, learned in October 2013 that a routine operation to remove fibroids from his wife, Amy Reed, had spread undetected leiomyosarcoma around her peritoneal cavity, turning a stage I cancer into a stage IV.

After what he called “serious infighting” at Harvard Medical School’s Brigham and Women’s Hospital in Boston, Massachusetts, where he worked at the time and where the operation was performed, the hospital banned the procedure, which is performed …
A transgenic mouse model demonstrating the oncogenic role of mutations in the polycomb-group gene EZH2 in lymphomagenesis
Authors: Tobias Berg, Silvia Thoene, Damian Yap, Tracee Wee, Nathalie Schoeler, Patty Rosten, Emilia Lim, Misha Bilenky, Andrew J. Mungall, Thomas Oellerich, Sherry Lee, Courteney K. Lai, Patricia Umlandt, Anisa Salmi, Harry Chang, Lisa Yue, David Lai, S.-W. Grace Cheng, Ryan D. Morin, Martin Hirst, Hubert Serve, Marco A. Marra, Gregg B. Morin, Randy D. Gascoyne, Samuel A. Aparicio, R. Keith Humphries
Journal: Blood (2014)
Sodium-hydrogen exchange and glucose transport in renal microvillus membrane vesicles from rats with diabetes mellitus.
Authors: R C Harris, B M Brenner, J L Seifter
Journal: Journal of Clinical Investigation (1986)

Diabetes mellitus is associated with important changes in renal hemodynamics and transport function. Disturbances in solute transport have also been characterized in nonrenal tissues during hyperglycemia and insulinopenia. The purpose of this study was to determine if diabetes is associated with adaptive changes in function of the brush-border membrane of the proximal tubule. We studied Na+ and glucose transport in rat microvillus membrane vesicles isolated from the renal cortex of streptozotocin-induced and BB/W autoimmune diabetic rats. Untreated diabetes was associated with an increase in pH-stimulated total and amiloride-sensitive 22Na+ uptake into vesicles. Insulin treatment returned vesicle 22Na+ uptake to control levels. The increased Na+/H+ exchange was shown to be a result of increased net renal acid production rather than a specific response to insulinopenia because treatment with NaHCO3 also returned 22Na+ uptake to control levels. On the other hand, Na+-glucose cotransport, which was depressed in vesicles from untreated diabetics, returned to control levels with insulin but not NaHCO3 administration. This decreased Na+-glucose cotransport was not secondary to reduction in transport sites in untreated diabetics. These results show that in diabetes mellitus, increased Na+/H+ exchange activity is not the direct result of insulinopenia. However, the diabetic state appears to alter the functioning of the luminal Na+-glucose cotransporter.
Depressed-type early adenocarcinoma of the terminal ileum
Authors: K. Hotta, A. Tomori, T. Oyama, Y. Miyata
Journal: Endoscopy (2007)

Depressed-type neoplasm of the jejunum and the ileum has not yet been recognized. To the best of our knowledge, this is the first case of depressed-type primary adenocarcinoma of the ileum.
Differences in glycolytic capacity and hypoxia tolerance between hepatoma cells and hepatocytes
Authors: Doris Hugo-Wissemann, Irene Anundi, Werner Lauchart, Richard Viebahn, Herbert de Groot
Journal: Hepatology (1991)

Viability, glycolytic capacity and energy metabolism under anaerobic conditions were studied in the hepatoma cell lines HTC, FU5 and HepG2 and in rat and human hepatocytes using glucose and fructose as glycolytic precursors. During 6 hr of anaerobic incubation without additional substrate, viability decreased rapidly in FU5 and HTC cells, whereas viability of HepG2 cells was not significantly affected. In all tumor cells, 10 mmol/L glucose prevented hypoxic cell injury almost completely. Lactate formation from glucose was about five times higher than in hepatocytes under these circumstances. ATP content of the tumor cells remained almost constant under anaerobic conditions in the presence of glucose. Ten millimoles per liter of fructose diminished glycolysis in the hepatoma cells compared with glucose, ranging from 87% reduction in HTC cells to 43% reduction in HepG2 cells. Accordingly, ATP content decreased rapidly in the FU5 and slowly in the HepG2 cells. Viability was strongly diminished in the HTC and FU5 cells in the presence of fructose, whereas in the HepG2 cells no effect of fructose on viability was detectable. In contrast to the hepatoma cells, rat and human hepatocytes exhibited higher rates of anaerobic glycolysis in the presence of fructose and thus were able to maintain their viability under these conditions. These differences in glycolytic capacity, energy metabolism and hypoxia tolerance of hepatoma cells compared with hepatocytes may be used for the treatment of liver cancer by isolated liver perfusion and ex situ revision of the organ.
ACHLORHYDRIA IN GALLBLADDER DISEASE
Authors: None GATEWOOD
Journal: JAMA (1923)

Owing to the frequency of epigastric distress in gallbladder disease, the notion has crept into the minds of many medical men ( Simnitzky,<sup>1</sup>Griffiths<sup>2</sup>and others) that hyperacidity is apt to be an accompaniment, if not a symptom, of cholelithiasis. That an absence of free hydrochloric acid, or an achylia, more often exists does not seem to be generally recognized, although a number of articles have appeared, from time to time, calling attention to it. Leva,<sup>3</sup>in 1893, was the first to note achylia in patients with gallstones, but the number of his cases was small and part of them so complicated that he drew no conclusions. Little is to be found in the literature following Leva's report until Glaser's<sup>4</sup>work in 1905. He stated that hypochlorhydria was of frequent occurrence in the patient who had presented gallstone symptoms for a long time. Hohlweg's<sup>5</sup>reports in
Late Recurrence of Minimal Lesion Nephrotic Syndrome
Authors: CESAR PRU
Journal: Annals of Internal Medicine (1984)

Nephrotic syndrome recurred in 16 patients who had been free of the disease for an interval of 4 to 25 years. Their initial illness began in childhood and responsed to adrenocorticosteroid therapy; in 10 patients it was associated with few changes on light microscopic examination of kidney biopsy specimens. The late recurrence also responded to steroids, and in only 1 patient did low-grade proteinuria persist after treatment. Renal biopsy specimens taken from 8 patients during late recurrence showed minimal-change nephrotic syndrome in 7 and focal segmental glomerulosclerosis in 1. Renal function remained normal in all patients. The late recurrence of minimal-change nephrotic syndrome has most of the features of that syndrome seen in the more typical childhood age group and should be managed similarly.
744 HEME OXYGENASE REGULATES THE RESPONSE OF INTRARENAL ARTERIES TO ALPHA-ADRENERGIC STIMULATION IN EXPERIMENTAL CIRRHOSIS
Authors: M. Di Pascoli, F. Zampieri, A. Piva, C. Merkel, A. Gatta, D. Sacerdoti, M. Bolognesi
Journal: Journal of Hepatology (2009)
Shall The Journal be Removed to Washington?
Authors: Gustavus S. Franklin
Journal: JAMA (1891)

<h3>To the Editor:</h3> I prefer Chicago as the location and home of our journal for one good reason, in addition to the many others already stated by numerous correspondents. I believe the Eastern members of our profession are tainted with heretical opinions as to the propriety and practicability of our "Code of Medical Ethics" as a guide to the highest honor and truest success of the profession. Witness the heterodoxy through which we have only recently passed and fresh in the minds of all. This reflection is not meant to impugn the characters of Eastern members generally—simply as a statement of a deplorable fact, as to a few in high places. Chillicothe, O., Feb. 3, 1891.
Diagnostic Tests for Lyme Disease-Reply
Authors: Daniel G. Miller
Journal: JAMA (1990)

<h3>In Reply.—</h3> Drs Feder and Rosenthal describe the clinical history of a patient who had an adverse drug reaction from treatment for a presumed diagnosis of Lyme borreliosis. From this evidence they conclude that the diagnostic criteria for this disease should be based on clinical evidence, with laboratory testing playing a secondary role. This approach to the diagnosis of Lyme borreliosis will find general concurrence in both the clinical community and those organizations that provide laboratory testing services. The further conclusion, that the urine antigen test is uninterpretable, may come as a surprise to the clinicians currently using the results of this assay, along with clinical evidence, in the treatment of patients with Lyme borreliosis. Our experience covers nearly 11000 determinations from 8000 patients tested for Lyme borreliosis—for 6000 of whom simultaneous clinical data exist. Approximately 15% of our specimens are positive. False-positive results, as in most laboratory assays,
Sudden death in a child following jellyfish envenomation by Chiropsalmus quadrumanus. Case report and autopsy findings
Authors: K. Bengtson
Journal: JAMA (1991)

Sudden death following coelenterate envenomation is not uncommon in Australia where the Pacific box jellyfish is indigenous. However, few cases of sudden fatal reactions have been reported in the Northern Hemisphere, and those that have occurred have all been attributed to the Portuguese man-of-war, Physalia physalis. We report the case of a child who died within 40 minutes of accidental envenomation with tentacles of a jellyfish, Chiropsalmus quadrumanus, and describe the findings at autopsy. This coelenterate may be of special danger to small children.
Atropine and Acute Myocardial Infarction
Authors: ANDREW L. WIT, PAUL F. CRANEFIELD
Journal: Circulation (1973)

has raised interesting and clinically important questions concerning the effects of heart rate on the incidence and severity of cardiac arrhythmias.These authors question the prevailing view that bradyeardia after acute myocardial infarction is asso- ciated with an increased incidence of severe cardiac arrhythmias, and express some disagreement with the interpretation of experiments by Han et al. who have indicated that slowing the heart rate increases temporal dispersion of refractoriness, lowers fibrillation threshold, and increases the likelihood of severe ventricular arrhythmias and fibrillation.'In opposition to this view, Dr. Epstein refers to his own experiments which indicate that in the conscious dog factors which tend to increase heart rate will increase the incidence and severity of cardiac arrhythmias after acute myocardial infarction.This was also shown in the experiments of Scherlag et al.2 Are these opposing views reconcilable?This is an important question since the tendency today is to treat bradyarrhythmias with atropine or by other means which increase the heart rate.Our recent studies on reentry in isolated cardiac tissue suggest some answers to these questions.3 4 Our results show that reentry can be brought about in isolated Purkinje fiber bundles by the presence of slow conduction in depressed cardiac fibers.Such reentry occurs readily at a low stimulus rate, but conduction in
Oral bisphosphonates and atrial fibrillation
Authors: Sumit R Majumdar
Journal: BMJ (2008)

The risk is negligible, and does not offset the benefits of reducing fractures

The benefits of bisphosphonates for the prevention of fracture in patients with osteoporosis are not disputed,1 2 and one trial has also reported reduced mortality in these patients.3 Nevertheless, bisphosphonates are underused by those most likely to benefit—elderly patients with fractures.2 This shortfall in care was difficult to rectify even while bisphosphonates were considered effective and safe,2 but matters will probably get worse after recent reports that these drugs might increase the risk of atrial fibrillation.3 4 5 6 Even fewer eligible patients are now likely to start taking bisphosphonates, and more treated patients are likely to stop taking them. This would be justified if the risk of atrial fibrillation were real and large enough to offset the known benefits for fracture reduction. However, this potentially increased risk is challenged by an accompanying population based observational study by Sorensen and colleagues, which finds no significant increase in atrial fibrillation or flutter in women taking bisphosphonates for osteoporosis.7

It was only a matter of time before osteoporosis, its treatments, and cardiovascular events were linked.8 9 Osteoporosis is common, it …