tbuckley/cabot-search huggingface dataset:
Acquisition of Epithelial-Mesenchymal Transition Phenotype of Gemcitabine-Resistant Pancreatic Cancer Cells Is Linked with Activation of the Notch Signaling Pathway
Authors: Zhiwei Wang, Yiwei Li, Dejuan Kong, Sanjeev Banerjee, Aamir Ahmad, Asfar Sohail Azmi, Shadan Ali, James L. Abbruzzese, Gary E. Gallick, Fazlul H. Sarkar
Journal: Cancer Research (2009)

Abstract Despite rapid advances in many fronts, pancreatic cancer (PC) remains one of the most difficult human malignancies to treat due, in part, to de novo and acquired chemoresistance and radioresistance. Gemcitabine alone or in combination with other conventional therapeutics is the standard of care for the treatment of advanced PC without any significant improvement in the overall survival of patients diagnosed with this deadly disease. Previous studies have shown that PC cells that are gemcitabine-resistant (GR) acquired epithelial-mesenchymal transition (EMT) phenotype, which is reminiscent of “cancer stem-like cells”; however, the molecular mechanism that led to EMT phenotype has not been fully investigated. The present study shows that Notch-2 and its ligand, Jagged-1, are highly up-regulated in GR cells, which is consistent with the role of the Notch signaling pathway in the acquisition of EMT and cancer stem-like cell phenotype. We also found that the down-regulation of Notch signaling was associated with decreased invasive behavior of GR cells. Moreover, down-regulation of Notch signaling by siRNA approach led to partial reversal of the EMT phenotype, resulting in the mesenchymal-epithelial transition, which was associated with decreased expression of vimentin, ZEB1, Slug, Snail, and nuclear factor-κB. These results provide molecular evidence showing that the activation of Notch signaling is mechanistically linked with chemoresistance phenotype (EMT phenotype) of PC cells, suggesting that the inactivation of Notch signaling by novel strategies could be a potential targeted therapeutic approach for overcoming chemoresistance toward the prevention of tumor progression and/or treatment of metastatic PC. [Cancer Res 2009;69(6):2400–7]
MEDICAL EDUCATION, 1909-1924
Authors: ABRAHAM FLEXNER
Journal: JAMA (1924)

Fifteen years ago, under the kindly and patient chaperonage of Dr. Colwell, I began my pilgrimage to medical schools at New Orleans, where Dr. Colwell and I visited the medical department of Tulane University. For three or four years following I devoted myself exclusively to the study and observation of medical education in this country and in the main countries of western Europe. Then for a period of ten years my contact with medical schools was simply occasional, while Dr. Colwell, in behalf of the Council on Medical Education of the American Medical Association, kept up not only his field contacts but also the unremittent hammering to which our American progress in medical education has been so largely due. About two and one-half years ago, I undertook to review once more the entire field, though unfortunately I have not been able to visit as many schools either in this country
HOSPITAL AND WARD CLINICAL LABORATORIES.
Authors: C. N. B. CAMAC
Journal: JAMA (1900)

When I was given the opportunity some months ago by the chairman of this Section to present a paper before the Association, I was and am still interested in the subject expressed in the title of this paper—"Hospital and Ward Clinical Laboratories." I hesitated, however, in bringing such a subject before you, as I felt that a report upon work done along medical lines would form a more appropriate paper. I submitted this question of the propriety of the subject to your chairman, and upon receiving his approval and encouragement felt reassured. I feel, nevertheless, that a subject touching the administration of a hospital, as this does, must be discussed by those who have experience in hospital management. The points, therefore, set forth in this paper represent the immediate needs of the visiting physician and teacher; these points, however, must be placed before those who are competent to speak for
Effects of Folic Acid Supplementation on Hearing in Older Adults
Authors: Jane Durga, Petra Verhoef, Lucien J.C. Anteunis, Evert Schouten, Frans J. Kok
Journal: Annals of Internal Medicine (2007)

Age-related hearing loss is a common chronic condition of elderly persons. Low folate status has been associated with poor hearing.To determine whether folic acid supplementation slows age-related hearing loss.Double-blind, randomized, placebo-controlled trial conducted from September 2000 to December 2004.The Netherlands.728 older men and women recruited from municipal and blood bank registries with plasma total homocysteine concentrations 13 micromol/L or greater serum and vitamin B12 concentrations 200 pmol/L or greater at screening, and no middle ear dysfunction, unilateral hearing loss, or pathologic ear conditions unrelated to aging.Daily oral folic acid (800 microg) or placebo supplementation for 3 years.3-year change in hearing thresholds, assessed as the average of the pure-tone air conduction thresholds of both ears of the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz) frequencies.Initial median hearing thresholds were 11.7 dB (interquartile range, 7.5 to 17.5 dB) for low frequencies and 34.2 dB (interquartile range, 22.5 to 50.0 dB) for high frequencies. Sixteen participants (2%) were lost to follow-up. After 3 years, thresholds of the low frequencies increased by 1.0 dB (95% CI, 0.6 to 1.4 dB) in the folic acid group and by 1.7 dB (CI, 1.3 to 2.1 dB) in the placebo group (difference, -0.7 dB [CI, -1.2 to -0.1 dB]; P = 0.020). Folic acid supplementation did not affect the decline in hearing high frequencies.The strict criterion for participation on the basis of serum homocysteine concentrations limits extrapolation to the general population. Folic acid fortification of food was prohibited in the Netherlands during the study, so baseline folate levels in participants were about half of those found in the U.S. population.Folic acid supplementation slowed the decline in hearing of the speech frequencies associated with aging in a population from a country without folic acid fortification of food. The effect requires confirmation, especially in populations from countries with folic acid fortification programs. Clinicaltrials.gov identifier: NCT00110604.
TOTALLY EPICARDIAL CARDIAC RESYNCHRONIZATION THERAPY CONCOMITANTLY WITH CORONARY ARTERY BYPASS GRAFTING IN PATIENTS WITH ISCHEMIC HEART FAILURE: THREE-YEAR RESULTS OF RESCUE STUDY
Authors: Alexander Romanov, Evgeny Pokushalov, Daria Prokhorova, Alexander Chernyavskiy, Vitaliy Shabanov, Kinga Goscinska-Bis, Jaroslaw Bis, Andrzej Bochenek, Borut Gersak, Alexander Karaskov
Journal: Journal of the American College of Cardiology (2013)
Cocaine-induced liver injury in mice elicits specific changes in DNA ploidy and induces programmed death of hepatocytes
Authors: María Cascales, Alberto Alvarez, Pilar Gascó, Lourdes Fernández-Simón, Nuria Sanz, Lisardo Boscá
Journal: Hepatology (1994)

Liver injury was induced by a single dose (60 mg/kg) of cocaine in male albino Swiss mice untreated or pretreated with phenobarbital (in drinking water 1 gm/L), for 5 days before cocaine administration. One parameter of liver injury, serum isocitrate dehydrogenase activity, showed sharp increases at 24 hr of cocaine treatment; we also noted decrease hepatic levels of ATP, GSH, cytochrome P-450 and NADPH/NADP+ ratio and increases in malondialdehyde concentration. Histopathological study of liver slices showed perivenous and periportal necrosis induced by cocaine in untreated mice and mice pretreated with phenobarbital, respectively. A regenerative postnecrotic response, which peaked at 48 hr, was demonstrated by the appearance of mitotic cells. Mitotic index analysis showed that proliferative cells appear to be unevenly distributed in the hepatic acinus and were mainly located in the vicinity of the damaged acinar region. Genomic DNA ploidy and the distribution of DNA in the phases of the cell cycle were studied in nuclei of isolated hepatocytes. At 12 hr of cocaine administration, both in untreated and phenobarbital-pretreated mice, the following changes were observed: a sharp decrease in tetraploid (4N) cells (40% to 17% and 25% to 6%, respectively) and octoploid (8N) cells (5% to 2% and 2% to 1%, respectively), together with the appearance of a hypodiploid population (13% and 31%, respectively). Hypodiploid population was characterized as apoptotic cells by detection of DNA fragmentation in agarose gel. These results suggest that a significant percentage of cell death induced by cocaine occurs by means of the apoptosis death program. Comparison of the initial values of DNA ploidy with those obtained at 7 days of cocaine administration showed remarkable increases in polyploid populations (4N and 8N) and a decrease in diploid cells (2N), indicating that the process of differentiation occurs when liver restores its functionality.
Persistent Chest Pain and No Obstructive Coronary Artery Disease
Authors: Anita Phan
Journal: JAMA (2009)

Patients with persistent chest pain and no obstructive coronary artery disease are often labeled as having noncardiac pain and not offered further cardiologic testing or treatment. Diagnostic uncertainty for persistent chest pain is associated with adverse quality of life, morbidity, and health care costs. Two underdiagnosed cardiac causes for persistent chest pain include microvascular coronary disease and abnormal cardiac nociception. Microvascular coronary disease is associated with an increased risk of adverse cardiovascular events such as myocardial infarction, congestive heart failure, and sudden cardiac death, and treatment directed at improving endothelial function can improve outcomes. Abnormal cardiac nociception is also a cause for persistent chest pain caused by heightened coronary pain perception. Coronary reactivity testing allows for direct measurement of blood flow characteristics in response to vasoactive agents for the diagnoses of microvascular coronary disease and can be a useful tool to differentiate causes of chest pain. Coronary reactivity testing is an invasive method for assessing coronary vascular function, with current evidence suggesting that its associated risk is relatively low compared with the adverse prognosis associated with microvascular coronary dysfunction. Accurate diagnosis in patients with persistent chest pain and normal coronary arteries can be challenging and deserves adequate investigation in light of the associated morbidity, mortality, and health care costs.
Myoedema in the 1930's
Authors: Alan R. Laurain
Journal: JAMA (1967)

<h3>To the Editor:—</h3> The letter from Drs. Lenthall and Donovan (Myoedema in the Detection of Hypoalbuminemia,<b>198</b>:329, 1966) evoked in me a feeling of nostalgia for my youth—lost in the Great Depression of the 1930's. Boys and girls in those days often produced these "knots" with a sharp, karate-like blow to the biceps of an unsuspecting victim. It was commonly recognized that the "ridges" could be produced more easily in some individuals than in others. Furthermore, practitioners of this game knew that the size and duration of the welt was roughly proportional to the force exerted, that the muscle must be completely relaxed when the blow is delivered, and that<i>everyone gets "lumps" if properly struck</i>. Those who did not get them invariably had tensed the biceps in anticipation of the blow. This is why such individuals could be made to show this phenomenon only when stealthily approached and
On the Action of Chloroform
Authors: J. White
Journal: BMJ (1857)

much difficulty.He went to sleep for an hour and a half this morning, and has been much quieter since.He is now lying quietly, with his eyes closed, and seems much inclined to sleep.November 7th.He is quiet and rational.He was ordered to take a dose of his mixture every four hours.November 9th.He was ordered to take his medicine three times a day.November 14th.He complains of a difficulty in passing urine, and of feeling cold when out of bed.He sleeps badly.He was ordered to omit the mixture, and to take three times a day five minims of dilute sulphuric acid in decoction of cinchona bark; and to have full diet, with a pint of beer daily.A small abscess formed near the anus, which was opened.With this exception, he progressed rapidly towards recovery, and was discharged cured on Decemnber 2nd.There are some remainina points in connexion with these fevers to which I might allude; but, as I can throw no addi- tional light upon them, I shall not trespass further upon your attention.
Renal Transplants and Renal Tumors
Authors: John P. Merrill
Journal: JAMA (1969)

Elsewhere in this issue Jochimsen et al (p 1721) report the effective treatment of advanced renal failure in a patient with tuberculous sclerosis, a disease associated with multiple hamortomas. In their patient the diseased kidneys also contained bilateral clear cell tumors which were indistinguishable from renal cell adenocarcinoma. This patient was alive and well four years after transplantation, with no evidence of recurrence of spread of malignancy. Presumably she received standard immunosuppressive therapy with azathioprine and prednisone. The investigators believe that renal tumors are, therefore, no contraindication to transplantation and they quote several other instances in which transplantation has been done for hypernephroma and for Wilms' tumor without evidence of recurrent disease. They purposely omit from their discussion the real and potential problem of the use of immunosuppressive therapy in patients with potential or established malignancies. With one exception, that of malignant melanoma, the transplantation of malignant cells from one
Combined Stimulation with Interleukin-18 and CpG Induces Murine Natural Killer Dendritic Cells to Produce IFN-γ and Inhibit Tumor Growth
Authors: Umer I. Chaudhry, T. Peter Kingham, George Plitas, Steven C. Katz, Jesse R. Raab, Ronald P. DeMatteo
Journal: Cancer Research (2006)

Abstract Natural killer dendritic cells (NKDC) are a novel subtype of dendritic cells with natural killer (NK) cell properties. IFN-γ is a pleiotropic cytokine that plays an important role in the innate immune response to tumors. Based on our previous finding that the combination of Toll-like receptor 9 ligand CpG and interleukin (IL)-4 stimulates NKDC to produce IFN-γ, we hypothesized that NKDC are the major IFN-γ-producing dendritic cell subtype and may play a significant role in the host antitumor response. We found that under several conditions in vitro and in vivo NKDC accounted for the majority of IFN-γ production by murine spleen CD11c+ cells. IL-18 alone induced NKDC to secrete IFN-γ, and the combination of IL-18 and CpG resulted in a synergistic increase in IFN-γ production, both in vitro and in vivo. NK cells made 26-fold less IFN-γ under the same conditions in vitro, whereas dendritic cells produced a negligible amount. The mechanism of IFN-γ secretion by NKDC depended on IL-12. NKDC selectively proliferated in vitro and in vivo in response to the combination of IL-18 and CpG. Systemic treatment with IL-18 and CpG reduced the number of B16F10 melanoma lung metastases. The mechanism depended on NK1.1+ cells, as their depletion abrogated the effect. IL-18 and CpG activated NKDC provided greater tumor protection than NK cells in IFN-γ−/− mice. Thus, NKDC are the major dendritic cell subtype to produce IFN-γ. The combined use of IL-18 and CpG is a viable strategy to potentiate the antitumor function of NKDC. (Cancer Res 2006; 66(21): 10497-504)
Rapid Diagnosis of Amniotic-Fluid Infection by Gas-Liquid Chromatography
Authors: Michael G. Gravett, David A. Eschenbach, Carol A. Speigel-Brown, King K. Holmes
Journal: New England Journal of Medicine (1982)

AMNIOTIC-FLUID infection, a common event during pregnancy, occurs most frequently in association with rupture of membranes, particularly prolonged rupture, and with premature delivery. It has been an important cause of perinatal mortality.1 , 2 Only a portion of amniotic-fluid infections are clinically apparent intrapartum3; they are usually recognized only on the basis of maternal leukocytosis, maternal or fetal tachycardia, uterine tenderness and irritability, or foul-smelling amniotic fluid.4 These signs represent late findings of amniotic-fluid infections; contamination of the fluid by pathogenic bacteria probably occurs several hours before the appearance of clinical signs of infection.5 , 6 Because of the difficulty of applying clinical . . .
STUDIES ON THE QUANTITATIVE ACTION OF A SPECIFIC ENZYME IN TYPE III PNEUMOCOCCUS DERMAL INFECTION IN RABBITS
Authors: Kenneth Goodner, René Dubos
Journal: The Journal of Experimental Medicine (1932)

The enzyme which specifically decomposes the capsular polysaccharide of Type III Pneumococcus must be used in certain definite amounts in order to bring about the recovery of rabbits infected intradermally with this organism. The experiments reported in this paper indicate that the minimal amounts of enzyme required bear a definite relationship to the severity of the infection as gauged by the number of pneumococci present in the circulating blood.
Reprints and Countries
Authors: A. A. Nanji, D. J. Campbell
Journal: JAMA (1982)

<h3>To the Editor.—</h3> Being avid collectors of reprints, we thought that the information set out in the Table would be useful for others with a similar hobby. The study was done during a three-year period and included reprint requests from all specialties of medicine. One of us (D.J.C.) is also an amateur radio operator, and the pattern of cards received after radio contact is similar to that of reprints. The percentage of reprints honored correlates inversely with countries' rates of inflation. Statistical tests of significance were not performed, thus avoiding a calamity in international scientific communication. However, one point is clear; obviously, the Japanese have achieved technological success without relinquishing their ancient claim to world leadership in good manners.
IRON METABOLISM IN EXPERIMENTAL ANEMIA
Authors: P. F. Hahn, G. H. Whipple
Journal: The Journal of Experimental Medicine (1938)

In experimental anemia in dogs due to blood loss the term "available iron" as determined by the dipyridyl test has no physiological significance. Iron salts (100 per cent available by dipyridyl) given in optimum dose (560 mg. per 2 weeks) will cause a net production of 50 to 55 gm. hemoglobin above the control base line in anemic dogs. This means that an iron salt which is rated as 100 per cent available by the dipyridyl test is only 35 per cent physiologically available. The term "available iron (dipyridyl)" simmers down to iron not in the form of hematin compounds. The absorption of this "available iron" is conditioned by a great variety of factors, many unknown at this time. Iron is indeed an elusive sprite whose "availability" or comings and goings cannot be determined in dogs by dipyridyl-perhaps only in part by studies of absorption and excretion. Liver contains "available iron (dipyridyl)" but also organic factors influencing hemoglobin regeneration in anemia as liver ash contains only about 50 per cent the potency of the whole liver. One can readily dissociate the iron from other potent factors in various tissues. Fractions of heart, liver, spleen, and kidney may contain very little iron yet cause much hemoglobin regeneration in anemic dogs. No investigator has reported any condition of copper deficiency in man or dog. In fact, in anemias copper is usually above normal concentration in the liver. It is unlikely, therefore, that in experimental anemia in dogs and in the various anemias of man, any significance attaches to the intake of copper.
Cholic acid synthesis as an index of the severity of liver disease in man
Authors: W. C. McCormick, C. C. Bell, L. Swell, Z. R. Vlahcevic
Journal: Gut (1973)

Bile acid pool size and kinetics were determined in 17 patients with cirrhosis and 11 patients without liver disease and correlated with the severity of liver disease as determined by the usual clinical and laboratory criteria. In order to assess the severity of liver disease, a grading system was devised which assigned numerical values to various clinical signs and laboratory results. The total clinical score and the patients were divided into two groups of advanced (7-18 points) or mild (1-6 points) cirrhosis. The clinical rating was then correlated with the various aspects of bile acid metabolism. Cholic acid synthesis was markedly reduced in the early stages of cirrhosis and continued to decrease with the advancement of the liver disease. There was an inverse correlation between synthesis of cholic acid and the severity of cirrhosis. Nine of the 10 patients with advanced cirrhosis and a very low cholic acid synthetic rate (average 68 mg per day) died within one to 13 months from the start of the study. Patients with mild cirrhosis also had significantly reduced cholic acid synthesis (average 152 mg per day) but they all were well and alive three to 23 months after the study. In contrast, chenodeoxycholic acid synthesis was not markedly affected in either patients with mild or advanced cirrhosis. There was also a high degree of correlation between the fractional daily turnover rate of cholic acid and the severity of liver disease. The fractional daily turnover rate of cholic acid was greatly reduced (50%) in patients with advanced cirrhosis. Deoxycholic acid was reduced in patients with mild cirrhosis and virtually absent from the bile of patients with advanced cirrhosis. The findings of the present report provide evidence that cholic acid synthesis is a sensitive indicator of the hepatocellular damage, whereas chenodeoxycholic acid synthesis is relatively unaffected by cirrhosis. The selective alteration in cholic acid synthesis probably resides in a deficiency of one or more enzymes regulating the formation of the 3-keto, 7 alpha, 12 alpha-dihydroxy precursor of cholic acid.