tbuckley/cabot-search huggingface dataset:
Caffeine clearance by enzyme multiplied immunoassay technique: a simple, inexpensive, and useful indicator of liver function.
Authors: J E McDonagh, V V Nathan, I C Bonavia, G R Moyle, A R Tanner
Journal: Gut (1991)

The clinical value and sensitivity of serum caffeine clearance measurement has been evaluated as an indicator of hepatic disease. After a 17 hour caffeine exclusion period, 300 mg of caffeine citrate was administered orally to the study subjects. Serum samples were taken four and 16 hours later. Serum caffeine concentrations were measured using an enzyme multiplied immunoassay technique (EMIT) and a clearance value derived. Conventional liver function tests were measured at the same time. A total of 103 subjects attending the medical unit in a district general hospital were studied. Twenty one had alcoholic liver disease, 11 non-alcoholic cirrhosis, nine non-cirrhotic liver disease, 21 suspected liver disease, six hepatic tumours, and 35 were hospital and normal control subjects. Caffeine clearance values were lowest in subjects with alcoholic liver disease (median 0.19 ml/min/kg, range 0.04-0.61 ml/min/kg) and significantly reduced in all subjects with liver disease (median 0.32 ml/min/kg, range 0.04-2.68 ml/min/kg) compared with control subjects (median 1.27 ml/min/kg, p less than 0.001). In subjects with suspected liver disease subsequently shown to have another explanation for abnormal liver function test results, caffeine clearance values were normal (median 1.31 ml/min/kg, range 0.23-2.64 ml/min/kg) and significantly different, p less than 0.001, from those of subjects with liver disease. Serum albumen values were not different for these latter two groups. Using a cut off value of 0.86 ml/min/kg, caffeine clearance measurement was 100% sensitive for alcoholic liver disease and 89% sensitive for all liver disease. The respective sensitivities for conventional liver function test measurement were 76% and 83%. In the suspected liver disease group, caffeine clearance was abnormal in only 24%, conventional liver function tests were abnormal in 95%. The respective specificities for caffeine clearance and liver function test measurement in control subjects were 93% and 100%. Caffeine clearance determined by EMIT is a simple inexpensive hepatic metabolic function test. This study indicates that it is a more sensitive indicator of structural liver disease than conventional liver function tests, especially for alcoholic liver disease. The test could be widely introduced as a useful, repeatable assessment of hepatic function.
LUNG GYMNASTICS IN THE TREATMENT OF CHRONIC DISEASE.Read by title in the Section on Practice of Medicine, at the Forty-fifth Annual Meeting of the American Medical Association, held in San Francisco, June 5-8, 1894.
Authors: L. P. WALBRIDGE
Journal: JAMA (1894)

Oxygen is the sustaining principle of animal life and of all the ordinary phenomena of combustion. It is indispensable in respiration, and in general is the most universally active and efficient element. Respiration is the most important function in the human economy. By this method life is sustained. When we consider the tremendous importance of the lungs it must become apparent that any neglect of these great central boilers of the body may result in disease. Man does not live by bread alone. The food we eat would not nourish us if we did not breathe. The air we breathe burns up the food, and by so doing produces energy and vital force. It is the air we breathe that supports combustion, and combustion maintains life by creating heat. But the ultimate source of the heat is contained in the potential energy taken into the body with the food we
The time course of action potential repolarization affects delayed afterdepolarization amplitude in atrial fibers of the canine coronary sinus.
Authors: B Henning, A L Wit
Journal: Circulation Research (1984)

The effects of changing the time course of action potential repolarization on the amplitude and coupling interval of delayed afterdepolarizations were studied in small preparations of coronary sinus atrial fibers exposed to catecholamines. Repolarization was accelerated or retarded by current pulses passed through an intracellular microelectrode in the depolarizing or repolarizing direction. Acceleration of repolarization decreased the amplitude of delayed afterdepolarizations, prolonged their coupling interval to the action potential upstroke, and prevented triggered activity. Prolonging the time for repolarization increased afterdepolarization amplitude, shortened the coupling interval, and caused triggered activity. The afterdepolarization amplitude and coupling interval had a linear relationship to the duration of the action potential plateau. In some preparations, the action potential plateau increased spontaneously at stimulation rates that caused afterdepolarization amplitude to increase and triggering to occur, and this may have contributed to the occurrence of triggering. The effects of action potential repolarization on delayed afterdepolarizations suggest that pharmacological agents such as antiarrhythmic drugs which alter action potential duration should influence afterdepolarizations. Drugs which shorten action potential duration might prevent triggered activity from occurring, whereas drugs which prolong duration might cause triggering.
Protection of the Head and Neck in Sports
Authors: E. S. Gurdjian
Journal: JAMA (1962)

Existing data on factors at work in athletic injuries to the head and neck are reviewed. Measurements have been made of the energies, accelerations, and changes of intracranial pressure involved in cases of concussion and skull fracture. In the cadaver, linear skull fractures can be produced by energies of 4.6 to 6.9 kg.m. These impart an average acceleration of 112 g and increase the intracranial pressure by about 1,450 mm. Hg. Such figures afford a basis for the construction of protective helmets. The thickness of padding required can be computed from the weight and velocity of the injuring object. If the velocity is doubled, the padding has to be 4 times thicker.
AN AGGREGATE OF PATHWAY-RELATED BIOMARKERS PREDICT RISK OF ACUTE MYOCARDIAL INFARCTION AND DEATH
Authors: Danny J. Eapen, Pankaj Manocha, Riyaz Patel, Muhammad Hammadah, Mohammad T. Kabbany, Emir Veledar, Christina Wassel, Suliman Alradawi, Frank Corrigan, Hatem Al Kassem, Ravi Nanjundappa, Nicholas Mantini, Kobina A. Wilmot, Joseph Poole, Robert Neuman, Dylan Malayter, Sergey Sikora, Laurence Sperling, Arshed Quyyumi, Stephen Epstein
Journal: Journal of the American College of Cardiology (2012)
Free radicals and breast cancer.
Authors: D C Malins
Journal: Environmental Health Perspectives (1996)

accurately describes our paper "Progression of Human Breast Cancers to the Metastatic State Is Linked to Hydroxyl Radical-induced DNA Damage" (1).However, it was claimed that Some scientists have questioned the methodologies used by Malins and note that studies published in the February 1996 issue of Carcinogenesis and the December 1995 issue of Chemical Research in Toxicology failed to duplicate Malins' initial results using identical methods.
Deficient Autophagy Results in Mitochondrial Dysfunction and FSGS
Authors: Takahisa Kawakami, Ivan G. Gomez, Shuyu Ren, Kelly Hudkins, Allie Roach, Charles E. Alpers, Stuart J. Shankland, Vivette D. D’Agati, Jeremy S. Duffield
Journal: Journal of the American Society of Nephrology (2014)

FSGS is a heterogeneous fibrosing disease of the kidney, the cause of which remains poorly understood. In most cases, there is no effective treatment to halt or retard progression to renal failure. Increasing evidence points to mitochondrial dysfunction and the generation of reactive oxygen species in the pathogenesis of CKD. Autophagy, a major intracellular lysosomal degradation system, performs homeostatic functions linked to metabolism and organelle turnover. We prevented normal autophagic pathways in nephrons of mice by mutating critical autophagy genes ATG5 or ATG7 during nephrogenesis. Mutant mice developed mild podocyte and tubular dysfunction within 2 months, profound glomerular and tubular changes bearing close similarity to human disease by 4 months, and organ failure by 6 months. Ultrastructurally, podocytes and tubular cells showed vacuolization, abnormal mitochondria, and evidence of endoplasmic reticulum stress, features that precede the appearance of histologic or clinical disease. Similar changes were observed in human idiopathic FSGS kidney biopsy specimens. Biochemical analysis of podocytes and tubules of 2-month-old mutant mice revealed elevated production of reactive oxygen species, activation of endoplasmic reticulum stress pathways, phosphorylation of p38, and mitochondrial dysfunction. Furthermore, cultured proximal tubule cells isolated from mutant mice showed marked mitochondrial dysfunction and elevated mitochondrial reactive oxygen species generation that was suppressed by a mitochondrial superoxide scavenger. We conclude that mitochondrial dysfunction and endoplasmic reticulum stress due to impaired autophagic organelle turnover in podocytes and tubular epithelium are sufficient to cause many of the manifestations of FSGS in mice.
Impact of Prophylactic Immediate Posttransplant Ganciclovir on Development of Transplant Atherosclerosis
Authors: Hannah A. Valantine, Shao-Zhou Gao, Santosh G. Menon, Dale G. Renlund, Sharon A. Hunt, Philip Oyer, Edward B. Stinson, Byron W. Brown, Thomas C. Merigan, John S. Schroeder
Journal: Circulation (1999)

Background —Coronary artery disease occurs in an accelerated fashion in the donor heart after heart transplantation (TxCAD), but the cause is poorly understood. The risk of developing TxCAD is increased by cytomegalovirus (CMV) infection and decreased by use of calcium blockers. Our group observed that prophylactic administration of ganciclovir early after heart transplantation inhibited CMV illness, and we now propose to determine whether this therapy also prevents TxCAD. Methods and Results —One hundred forty-nine consecutive patients (131 men and 18 women aged 48±13 years) were randomized to receive either ganciclovir or placebo during the initial 28 days after heart transplantation. Immunosuppression consisted of muromonab-CD3 (OKT-3) prophylaxis and maintenance with cyclosporine, prednisone, and azathioprine. Mean follow-up time was 4.7±1.3 years. In a post hoc analysis of this trial designed to assess efficacy of ganciclovir for prevention of CMV disease, we compared the actuarial incidence of TxCAD, defined by annual angiography as the presence of any stenosis. Because calcium blockers have been shown to prevent TxCAD, we analyzed the results by stratifying patients according to use of calcium blockers. TxCAD could not be evaluated in 28 patients because of early death or limited follow-up. Among the evaluable patients, actuarial incidence of TxCAD at follow-up (mean, 4.7 years) in ganciclovir-treated patients (n=62) compared with placebo (n=59) was 43±8% versus 60±10% ( P &lt;0.1). By Cox multivariate analysis, independent predictors of TxCAD were donor age &gt;40 years (relative risk, 2.7; CI, 1.3 to 5.5; P &lt;0.01) and no ganciclovir (relative risk, 2.1; CI, 1.1 to 5.3; P =0.04). Stratification on the basis of calcium blocker use revealed differences in TxCAD incidence when ganciclovir and placebo were compared: no calcium blockers (n=53), 32±11% (n=28) for ganciclovir versus 62±16% (n=25) for placebo ( P &lt;0.03); calcium blockers (n=68), 50±14% (n=33) for ganciclovir versus 45±12% (n=35) for placebo ( P =NS). Conclusions —TxCAD incidence appears to be lower in patients treated with ganciclovir who are not treated with calcium blockers. Given the limitations imposed by post hoc analysis, a randomized clinical trial is required to address this issue.
Endothelial TNF Receptor 2 Induces IRF1 Transcription Factor-Dependent Interferon-β Autocrine Signaling to Promote Monocyte Recruitment
Authors: Deepak Venkatesh, Thomas Ernandez, Florencia Rosetti, Ibrahim Batal, Xavier Cullere, Francis W. Luscinskas, Yuzhi Zhang, George Stavrakis, Guillermo García-Cardeña, Bruce H. Horwitz, Tanya N. Mayadas
Journal: Immunity (2013)
Abstract 4899: Altered receptor glycosylation confers cisplatin resistance in ovarian and colon cancer cells
Authors: Matthew J. Schultz, Amanda F. Swindall, Susan L. Bellis
Journal: Cancer Research (2012)

Abstract Chemotherapy resistance is a significant clinical obstacle in the treatment of cancer. Platinum-based drugs are a mainstay of treatment in many solid cancers; however, tumor resistance to these drugs hampers long term efficacy. Resistance is multi-factorial, and theories to explain resistance are incomplete. In this study we report a novel mechanism for resistance to cisplatin involving changes in receptor glycosylation. Previous work in our lab has demonstrated enhanced colon cancer cell survival in cells expressing ST6Gal-I, a Golgi glycosyltransferase that adds the negatively-charged sugar, alpha2-6-linked sialic acid, to selected membrane proteins. We showed that sialylation of the Fas death receptor by ST6Gal-I decreases apoptotic signaling in response to Fas agonists by blocking DISC formation and receptor internalization. Elevated ST6Gal-I expression has been reported in many cancers, including ovarian and colon, and its expression is negatively correlated with patient prognosis. Interestingly, cisplatin has been demonstrated to mediate its cytotoxic effects, in part, through Fas receptor upregulation and activation, although the mechanism is not currently understood. Combining these results and observations, we investigated whether ST6Gal-I-mediated sialylation of the Fas receptor inhibits apoptotic signaling in response to cisplatin treatment, contributing to intrinsic cisplatin resistance. We determined the extent of cisplatin-induced apoptotic cell death by blotting for cleaved caspase-3, a terminal caspase, and detected decreased levels of activated caspase in ST6Gal-I expressing ovarian and colon cell lines. This result was observed in both a low endogenous ST6Gal-I cell model with forced ST6Gal-I expression, as well as a high endogenous ST6Gal-I expression cell model with shRNA ST6Gal-I knockdown. We also show sustained viability in cells expressing ST6Gal-I after cisplatin treatment by measuring a peptide protease substrate which is cleaved in live cells. Conversely, we detected a decrease in viability in non-ST6Gal-I expressing counterpart cell lines indicating that cells lacking ST6Gal-I expression are more sensitive to cisplatin-mediated cell death. Finally, we observed that cisplatin-mediated cell death is attenuated by treating cells with blocking antibodies to Fas, consistent with other studies implicating this receptor in cisplatin efficacy. Our findings suggest a novel mechanism contributing to platinum drug resistance in cancer cell populations and identify ST6Gal-I as a promising target for therapeutic intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4899. doi:1538-7445.AM2012-4899
Cells and "Coagulable Lymph"
Authors: C. Newman
Journal: BMJ (1972)

This is a difficult book to review.It is so interesting, Professor Rather is such a good medical historian, and the subject is so signi- ficant that the temptation to write an abstract of the original is irresistible: my first effort at this review was just that, and it was not nearly as good as the originaLThe capillary circulation, though guessed by Malpighi in 1661, was not actually seen until the early 1800's.It was promulgated from England over Europe in the 1820's, at the same time as Laennec's auscultation.The same period was that of massive therapeutic
Alloreactive natural killer cells in targeting high-risk leukaemias
Authors: L Moretta, F Locatelli, A Moretta
Journal: Annals of the Rheumatic Diseases (2008)

Natural killer (NK) cells express surface receptors that regulate potent effector functions, such as cytolytic activity and release of cytokines, which play a central role in inflammatory response and immunoregulation. In this paper, major advances are outlined from the original discovery of HLA-class I-specific inhibitory receptors in humans to recent, particularly successful, clinical applications in the cure of high-risk, otherwise fatal leukaemias. The central role of donor-derived "alloreactive" NK cells in eradicating leukaemic cells in the T-cell-depleted haploidentical haematopoietic stem cell transplantation setting became evident. Since alloreactive NK cells seem to play a key role also in preventing graft rejection and graft-vs-host disease, they may be an ideal tool to treat high-risk leukaemias in the haematopoietic stem cell transplantation setting.
Akt Like a Woman
Authors: Peter H. Sugden, Angela Clerk
Journal: Circulation Research (2001)

he oncogenic murine AKT8 retrovirus was identified almost 25 years ago, and the presence of the causative oncogenic agent v-akt was subsequently demonstrated in transformed cells or tumors from both mice and humans. 1,2he cellular homolog of v-akt was cloned in the early 1990s and was termed c-Akt (or simply Akt).Largely on the basis of its sequence similarity to both protein kinases A and C, it was concluded that Akt (alternatively known as protein kinase B [PKB]) represented a Ser-/Thr-protein kinase.Three mammalian genes have been identified, with transcripts of akt1 and akt2 being highly expressed in heart.The explosion of interest in Akt was the direct consequence of the realization that it is an effector of the lipid signaling molecule phosphatidylinositol 3,4,5trisphosphate [PtdIns(3,4,5)P 3 ] (Figure ).By binding to their transmembrane receptor protein tyrosine kinases, a variety of growth factors, including insulin and insulin-like growth factor 1 (IGF1), activate the lipid kinase phosphatidylinositol 3-kinase (PI3K) to phosphorylate the membrane phospholipid PtdIns(4,5)P 2 , producing PtdIns(3,4,5)P 3 .PtdIns(3,4,5)P 3 remains in the plane of the membrane and may serve to recruit Akt to this compartment from its normal cytoplasmic location by binding to the Akt pleckstrin-homology domain. 1,2In addition, PtdIns(3,4,5)P 3 activates PtdIns(3,4,5)P 3 -dependent protein kinase, which phosphorylates Akt on a Thr-residue (Thr 308 in Akt1/PKB␣, Thr 309 in Akt2/PKB␤, and Thr 305 in PKB␥). 2 Activation of Akt1/PKB␣ and Akt2/PKB␤ also requires phosphorylation of Ser 473 and Ser 474 , respectively, although the kinase involved is not clear and the site is absent from PKB␥.After activation of Akt, the signaling pathway diverges, with Akt stimulating a variety of anabolic processes, including glucose uptake and glycogen synthesis, translational protein synthesis, and, by increasing resistance to or delaying apoptosis, cell survival.Although many of the processes modulated by Akt are cytoplasmic, activated Akt also translocates to the nucleus, 2 where it is presumably involved in the regulation of gene expression.
Transfusion Reactions from Contaminated Blood
Authors: Abraham I. Braude
Journal: New England Journal of Medicine (1958)

THE saprophytic bacteria that inhabit the premises where blood is collected, stored or transfused sometimes enter the bottles through carelessness and contaminate the blood itself. If large numbers of these contaminants are present in the transfused blood, they may lead to reactions, the violence of which depends on the properties of the contaminant. Gram-positive saprophytes, such as diphtheroids, have produced only fever and no serious constitutional disturbances.1 Gram-negative saprophytes, on the other hand, have been responsible for a type of overwhelming shock that is almost invariably fatal.2 3 4 5 Bacteremic shock induced by gram-negative bacilli usually occurs as a complication during the . . .
A SLIGHT IMPROVEMENT IN THE TECHNIC OF INTRAUTERINE PACKING
Authors: Paul E. Spangler
Journal: JAMA (1926)

It occasionally becomes necessary during the course of an obstetric or surgical practice to pack the uterine cavity. It also occasionally occurs that more than one length of packing gauze is needed to fill the cavity. Unless difficulty is to be experienced in removing the gauze, it is essential that each successive strip of gauze be united firmly to the one that precedes it. In the past, the general practice has been to tie the ends of the strips together by means of the square knot. It has happened that, following the packing and after the physiologic contraction of the cervix, the large bulk of the knotted gauze so formed offers considerable resistance to easy removal. The difficulty so encountered has been so severe as to make necessary a general anesthetic and a minor operative procedure to secure adequate room for the removal of the gauze knot. It was to overcome this difficulty that the procedure described here was devised.
“The city of Hepar”: Rituals, gastronomy, and politics at the origins of the modern names for the liver
Authors: Michele Augusto Riva, Enrica Riva, Mauro Spicci, Mario Strazzabosco, Marcello Giovannini, Giancarlo Cesana
Journal: Journal of Hepatology (2011)

Medical etymology sometimes provides unexpected information about health concepts and medical practice in different times and cultures. We conducted an etymological analysis of the terms used to indicate "liver" in Germanic and Romance languages. The Greek word "hèpar" was originally connected to the concept of "pleasure", showing that in antiquity the liver was considered to be the seat of soul and human feelings. In Romance languages, the Latin term "ficatum" was linked to the ancient practice of fattening geese with figs (ficus in Latin) to make their livers more delicious. This relationship between the liver, fat, and carbohydrates seems to indicate that ancient gourmets had clear knowledge of the nutritional mechanisms underlying "fatty liver" in animals. On the other hand, the Germanic term "lifere" was initially connected to "life", underscoring the relation of the liver to health and existence. In the Early Modern Age, the liver became a recurring image in political reflection, especially within the Elizabethan tradition of the body politic, where the king was frequently described as the "liver" of his country. Finally, the liver was used to indicate courage, or the lack of it: some modern French and English idiomatic expressions derive from the ancient belief that people who had no blood in their liver ("lily-livered") would thus be cowards or betrayers.
Genetics of liver disease: From pathophysiology to clinical practice
Authors: Tom H. Karlsen, Frank Lammert, Richard J. Thompson
Journal: Journal of Hepatology (2015)

Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients.