tbuckley/cabot-search huggingface dataset:
Loss of the glycine N-methyltransferase gene leads to steatosis and hepatocellular carcinoma in mice
Authors: M. Luz Martínez‐Chantar, Mercedes Vázquez‐Chantada, Usue Ariz, Nuria Martínez, Marta Varela, Zigmund Luka, Antonieta Capdevila, Juan Rodríguez, Ana M. Aransay, Rune Matthiesen, Heping Yang, Diego F. Calvisi, Manel Esteller, Mario Fraga, Shelly C. Lu, Conrad Wagner, José M. Mato
Journal: Hepatology (2008)

Glycine N-methyltransferase (GNMT) is the main enzyme responsible for catabolism of excess hepatic S-adenosylmethionine (SAMe). GNMT is absent in hepatocellular carcinoma (HCC), messenger RNA (mRNA) levels are significantly lower in livers of patients at risk of developing HCC, and GNMT has been proposed to be a tumor-susceptibility gene for liver cancer. The identification of several children with liver disease as having mutations of the GNMT gene further suggests that this enzyme plays an important role in liver function. In the current study we studied development of liver pathologies including HCC in GNMT-knockout (GNMT-KO) mice. GNMT-KO mice have elevated serum aminotransferase, methionine, and SAMe levels and develop liver steatosis, fibrosis, and HCC. We found that activation of the Ras and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways was increased in liver tumors from GNMT-KO mice coincidently with the suppression of the Ras inhibitors Ras-association domain family/tumor suppressor (RASSF) 1 and 4 and the JAK/STAT inhibitors suppressor of cytokine signaling (SOCS) 1–3 and cytokine-inducible SH2-protein. Finally, we found that methylation of RASSF1 and SOCS2 promoters and the binding of trimethylated lysine 27 in histone 3 to these 2 genes was increased in HCC from GNMT-KO mice. Conclusion: These data demonstrate that loss of GNMT induces aberrant methylation of DNA and histones, resulting in epigenetic modulation of critical carcinogenic pathways in mice. (HEPATOLOGY 2008.)
The Vascular Component in Hemostasis
Authors: Armand J. Quick
Journal: New England Journal of Medicine (1970)

ACCORDING to the concept that hemostasis is the resultant of an evolutionary development,1 vascular contraction was the first and the most primitive phase. This was followed by the appearance of a blood cell possessing the property of agglutination, and the final phase was the acquisition of the ability to form a fibrin clot. Even today, the role of the vascular component is still poorly defined, and only two simple tests are available to the clinical laboratory for study of the vascular response when injury occurs — the bleeding time and the tourniquet test. Neither procedure has been rigidly standardized and . . .
gp100 Peptide Vaccine and Interleukin-2 in Patients with Advanced Melanoma
Authors: Douglas J. Schwartzentruber, David H. Lawson, Jon M. Richards, Robert M. Conry, Donald M. Miller, Jonathan Treisman, Fawaz Gailani, Lee Riley, Kevin Conlon, Barbara Pockaj, Kari L. Kendra, Richard L. White, Rene Gonzalez, Timothy M. Kuzel, Brendan Curti, Phillip D. Leming, Eric D. Whitman, Jai Balkissoon, Douglas S. Reintgen, Howard Kaufman, Francesco M. Marincola, Maria J. Merino, Steven A. Rosenberg, Peter Choyke, Don Vena, Patrick Hwu
Journal: New England Journal of Medicine (2011)

Stimulating an immune response against cancer with the use of vaccines remains a challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immune activating agent, could improve outcomes. In a previous phase 2 study, patients with metastatic melanoma receiving high-dose interleukin-2 plus the gp100:209-217(210M) peptide vaccine had a higher rate of response than the rate that is expected among patients who are treated with interleukin-2 alone.We conducted a randomized, phase 3 trial involving 185 patients at 21 centers. Eligibility criteria included stage IV or locally advanced stage III cutaneous melanoma, expression of HLA*A0201, an absence of brain metastases, and suitability for high-dose interleukin-2 therapy. Patients were randomly assigned to receive interleukin-2 alone (720,000 IU per kilogram of body weight per dose) or gp100:209-217(210M) plus incomplete Freund's adjuvant (Montanide ISA-51) once per cycle, followed by interleukin-2. The primary end point was clinical response. Secondary end points included toxic effects and progression-free survival.The treatment groups were well balanced with respect to baseline characteristics and received a similar amount of interleukin-2 per cycle. The toxic effects were consistent with those expected with interleukin-2 therapy. The vaccine-interleukin-2 group, as compared with the interleukin-2-only group, had a significant improvement in centrally verified overall clinical response (16% vs. 6%, P=0.03), as well as longer progression-free survival (2.2 months; 95% confidence interval [CI], 1.7 to 3.9 vs. 1.6 months; 95% CI, 1.5 to 1.8; P=0.008). The median overall survival was also longer in the vaccine-interleukin-2 group than in the interleukin-2-only group (17.8 months; 95% CI, 11.9 to 25.8 vs. 11.1 months; 95% CI, 8.7 to 16.3; P=0.06).In patients with advanced melanoma, the response rate was higher and progression-free survival longer with vaccine and interleukin-2 than with interleukin-2 alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00019682.).
SUGAR OF MILK AS AN ARTICLE OF FOOD IN CONSUMPTION AND OTHER PULMONARY DISEASES
Authors: J. Turnbull
Journal: BMJ (1853)

Juxz 24, fourth and fifth ribs, just under the nipple.The sounds at the apex were very indistinct, though a low soft murmur could be caught; at the base, a distinct rubbing to and fro sound ras heard.The heart's dulness appeared to extehd towards the costo-clavicular articulation.The pulse was 104, and thready.In the lungs, percussion was decidedly duller under the left clavicle than under the right.There were strong sibi- lant and sonorous rhonchi on both sides of the chest; mostly on the right side, where, in the clavicular region, the re- spiration was loud and blowing, and equal in length to the inspiration.On the left side, the expiration was prolonged, but not nearly as much so as on the right.Over the front of the abdomen, there was a rash of a blueish shade, disappearing under pressure; the patches varying in size fromi that of a fourpenny piece to a pin's head.The bowels were open; the appetite was good.The followving treatment was followed.A blister was applied over the heart, and the following mixture pre- scribed;-P Potassw-nitratis 3 ij.
The contribution of the capillary endothelium to blood clearance and tissue deposition of anionic quantum dots in vivo
Authors: Marc Praetner, Markus Rehberg, Peter Bihari, Max Lerchenberger, Bernd Uhl, Martin Holzer, Martin E. Eichhorn, Robert Fürst, Tamara Perisic, Christoph A. Reichel, Ulrich Welsch, Fritz Krombach
Journal: Biomaterials (2010)
Fluorouracil and Colorectal Cancer
Authors: Bernard Ecanow
Journal: JAMA (1977)

<h3>To the Editor.—</h3> The disagreement between Moertel (236:1935, 1976) and Li (237:872, 1977) regarding the value of fluorouracil as an adjuvant agent can be reconciled if the factors of angiogenesis and selective solubilization of fluorouracil are taken into account. It is evident that at the stage in which disseminated tumor cells are not yet vascularized; they are not accessible and, thus, largely invulnerable to such anticancer drugs as may be presented in the circulating blood. Further, in the unvascularized state, only limited growth of the tumor mass occurs.<sup>1</sup>While angiogenesis renders the tumor accessible to anticancer drugs, at the same time it also promotes an exponential rate of malignant cell growth.<sup>2</sup>The tumor growth rate that occurs after even a relatively short period of vascularization is such as to make it problematic whether in the individual case fluorouracil will be able to selectively overcome the kinetics of cancer cell
PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS POST SURGICAL REVASCULARISATION
Authors: Scot Garg, Giovanna Sarno, Juan Luis Gutiérrez-Chico, Joanna Wykrzykowska, Chrysafios Girasis, Peter de Jaegere, Arie-Peter Kappetein, Ron van Domburg, Patrick Serruys
Journal: Journal of the American College of Cardiology (2010)
Bilateral pneumothoraces, cystic lung disease and papular skin lesions in a young man
Authors: A R Haas, K L Nathanson
Journal: Thorax (2009)

A 36-year-old non-smoking Korean man presented to the emergency room with bilateral pleuritic chest pain and mild dyspnoea on exertion. His review of systems was negative. He had multiple family members across three generations with “lung disease”. His physical examination was notable for a normal body habitus, left greater than …
The Marijuana Smokers
Authors: Frank J. Ayd
Journal: JAMA (1971)

Of the many books on marihuana,<i>The Marijuana Smokers</i>is one of the best. Dr. Goode is an erudite, scientifically oriented sociologist, with an analytic and critical mind and a superb writing skill. With these assets and the knowledge acquired from extensive reading, from interviewing over 200 marihuana users, and from approximately 2,500 manhours spent observing pot smoking, he has written a book that will play an important role in ultimately formulating new attitudes toward marihuana usage. There is an urgent need for objective facts about this drug and its users. At present both the promarihuana and the antimarihuana people seem more intent on propagandizing their views than on discovering the truth. Dr. Goode wants to expose the misconceptions about cannabis by presenting the truth as he sees it. He begins with an overview of marihuana use and then draws an excellent portrait of a marihuana smoker. This is followed
Measurement of omission.
Authors: J T Hart
Journal: BMJ (1982)

Back in the 1960s, before rubella immunisation and the Abortion Act, a sixth (unwanted) pregnancy in a 42-year-old Glyncorrwg woman resulted in a child with severe brain damage. The mother had had no apparent illness,  there had been an epidemic of rubella in our village during the first weeks of her pregnancy. The whole family was affected: the father's smoking and alcohol problems went out of control into diabetes and coronary heart disease. As the child grew he became unmanageable; with all ground floor windows smashed and replaced by cardboard, the home became a cave. In the insensitive jargon of health econo? mists he became a high consumer of services, first diagnostically, later for special educational support, now (as his exhausted relatives die or capitulate) for the most costly service of all, full time residential care. So when rubella immunisation became possible, we wanted it to succeed. At that time secondary school absence was running at 20% in 13-year-olds at the local comprehensive, and at least this proportion was therefore presumably not immunised.  wrote to our local medical officer of health asking for a list of girls missed, so that we could get them immunised. I can give you the names of the ones we did, he wrote back, but how can  know the ones we didn't ?
Obama asks AMA to support his healthcare reform package
Authors: J. H. Tanne
Journal: BMJ (2009)

Addressing a meeting of the American Medical Association’s policy making House of Delegates in Chicago on 15 June, President Barack Obama has asked for the association’s support for his healthcare reform initiative.

The AMA, which represents about a quarter of doctors in the United States, expressed support and said it would evaluate all proposals for reform in the light of six principles: expanded coverage, improved quality, reform of government programmes, reduction of costs, greater focus on wellness and prevention, and reform of payment and delivery. An AMA spokeswoman said that the association was waiting to see what plans emerged from Congress.

In his speech President Obama said, “The status quo is unsustainable.” He said that the US is spending about 50% more on health care per person than the next most costly nation, yet “the quality of our care is often lower, and we aren’t any healthier.” He added: “In fact, citizens in some countries that spend less than we do are actually living longer …
Glycochenodeoxycholic acid inhibits calcium phosphate precipitation in vitro by preventing the transformation of amorphous calcium phosphate to calcium hydroxyapatite.
Authors: S M Qiu, G Wen, N Hirakawa, R D Soloway, N K Hong, R S Crowther
Journal: Journal of Clinical Investigation (1991)

Calcium hydroxyapatite can be a significant component of black pigment gallstones. Diverse molecules that bind calcium phosphate inhibit hydroxyapatite precipitation. Because glycine-conjugated bile acids, but not their taurine counterparts, bind calcium phosphate, we studied whether glycochenodeoxycholic acid inhibits calcium hydroxyapatite formation. Glycochenodeoxycholic acid (2 mM) totally inhibited transformation of amorphous calcium phosphate microprecipitates to macroscopic crystalline calcium hydroxyapatite. This inhibition was not mediated by decreased Ca2+ activity. Taurocholic acid (2-12 mM) did not affect hydroxyapatite formation, but antagonized glycochenodeoxycholic acid. Both amorphous and crystalline precipitates contained a surface fraction relatively rich in phosphate. The surface phosphate content was diminish by increasing glycochenodeoxycholic acid concentrations, and this relationship was interpreted as competition between bile acid and HPO4(-4) for binding sites on the calcium phosphate surface. A phosphate-rich crystal surface was associated with rapid transition from amorphous to crystalline states. These results indicate that glycochenodeoxycholic acid prevents transformation of amorphous calcium phosphate to crystalline hydroxyapatite by competitively inhibiting the accumulation of phosphate on the crystal embryo surface.
Meconium Peritonitis Due to Hole in the Foetal Intestinal Wall and Without Obstruction
Authors: A. W. Franklin, J. P. Hosford
Journal: BMJ (1952)

The presence of meconium in the foetal peritoneal cavity has long been recognized as a cause of intense chemical peritonitis. The visceral peritoneum becomes thickened to form a membrane encasing the intestines ; in it and in the thickened parietal peritoneum calcium is deposited, recognized radiologically (Neuhauser, 1944) and histologically (Falkenheim and Askanazy, 1892). In some cases there is a plastic peritonitis, in others gross ascites. Such changes are not infective, but infection is added when the normal intestinal bacteria appear on the third or fourth day of life. There is a mystery about the mechanism by which the meconium reaches the peritoneal cavity. Rupture of the intestinal wall does occur in both neonate and foetus in association with obstruction. Thelander (1939) has collected many reports of perforations at all levels of the gastro intestinal tract. At the end of the proximal segment, at the lowest part of the normally functioning gut, there may be dilatation with or without muscular hypertrophy, and this whether the cause of the obstruction be atresia, stenosis, bands or aberrant arteries, or MeckePs diverti culum, malrotation with kinking of the gut, inspissated meconium, or paralysis of Hirschsprung type (functional obstruction). Sooner or later, without relief of the obstruction this segment perforates. A neonatal perfora tion, occurring after the arrival of intestinal bacteria, causes bacterial peritonitis and pneumoperitoneum with signs of severe shock leading to death of the baby. Foetal perforation causing meconium peritonitis can be understood if it is accepted that the foetus swallows liquor amnii and the foetal intestinal wall moves in peristaltic waves. The statement made in 1915 by Rud new (quoted by Low et al, 1949), who collected 40 cases, is that in only half of them was there evidence of obstruction and, whether this proportion is accurate or not, a hole may be found without any obstruction. But why should there be a hole in the wall of what is appar ently a normally formed and normally acting intestine ? The mystery is further deepened by two more observa tions : cases of meconium peritonitis have been reported in newborn babies in whom the subsequent post mortem examination has failed to show any hole through which meconium could have escaped (Skiles, 1928) ; and in some cases, with a hole but without evidence of obstruc tion by inspissated meconium, pancreatic fibrosis is proved or suspected, as in Case 2 below. A full explana tion to account for all these observations is still lacking. It is possible that a foetus with meconium Heus may by vigorous peristalsis rupture the gut and relieve itself by passing the meconium into the peritoneal cavity, and that the perforation may even heal in some cases before birth.
The Metabolism of Proinsulin and Insulin by the Liver
Authors: A. H. Rubenstein, L. A. Pottenger, M. Mako, G. S. Getz, D. F. Steiner
Journal: Journal of Clinical Investigation (1972)

The removal of bovine proinsulin by the isolated perfused rat liver has been studied and the results compared with the removal of insulin. At high concentrations of insulin (> 180 ng/ml) the removal process was saturated and the t½ varied between 35 and 56 min. With low initial insulin levels the disappearance followed first-order kinetics, the mean regression coefficient being — 0.022, t½ 13.8 min, and the hepatic extraction 4.0 ml/min. The results with proinsulin were in striking contrast to these findings. At both high and low concentrations the hepatic removal of proinsulin was considerably slower, averaging 10-15 times less than that of insulin. Specific immunoassay techniques and gel filtration of samples taken from perfusions to which both labeled and unlabeled proinsulin had been added did not show conversion to either insulin or the C-peptide.
Preliminary Clinical Trials with 9-Alpha-Fluoro Hydrocortisone Acetate in Rheumatoid Arthritis
Authors: E. W. Boland, N. E. Headley
Journal: Annals of the Rheumatic Diseases (1954)

<h3>Purpose</h3> To evaluate aetiology, demographic profile, clinical features and outcomes in cases of peripheral ulcerative keratitis (PUK). <h3>Methods</h3> Seventy-six eyes of 65 consecutive patients with PUK were evaluated in this prospective interventional study over an 18 month period, which were followed for 3 years. The main outcome measures were sociodemographic profile, aetiology, clinical features, management strategies and outcome. <h3>Results</h3> Sixty per cent (39/65) of cases were men and mean age was 45.5±17.9 years. Two-thirds (43/65) of the patients were from rural areas with majority (48/65) belonging to low socioeconomic status. Unilateral disease was present in 83% of patients (54/65) with nasal involvement in 60.5% (46/76) cases. The most common aetiology was Mooren9s ulcer (31.5% cases (24/76 eyes)) followed by infection and systemic collagen vascular disease. Meibomian gland dysfunction (17/76: 22.3%) was the most common extraocular association and complicated cataract (12/76:15.7%) was the most common intraocular abnormality. In mild and moderate cases, no significant visual improvement was observed (p=0.085 and p=0.156) as compared with the pretreatment status. Surgical treatment was successful in maintaining anatomical integrity in 83.3% (30/36) eyes. Recurrence of the disease was seen in one eye in moderate disease and three eyes in severe disease. <h3>Conclusions</h3> Mooren9s ulcer followed by collagen vascular diseases and infection are important causes of PUK in developing countries. Surgical intervention in perforated cases had good anatomical success and visual prognosis.
Specific platelet mediators and unstable coronary artery lesions. Experimental evidence and potential clinical implications.
Authors: J T Willerson, P Golino, J Eidt, W B Campbell, L M Buja
Journal: Circulation (1989)

We have speculated previously that the abrupt conversion from chronic stable to unstable angina and the continuum to acute myocardial infarction may result from myocardial ischemia caused by progressive platelet aggregation and dynamic vasoconstriction themselves caused by local increases in thromboxane and serotonin at sites of coronary artery stenosis and endothelial injury. Platelet aggregation and dynamic coronary artery vasoconstriction probably result from the local accumulation of thromboxane and serotonin and also relative decreases in the local concentrations of endothelially derived vasodilators and inhibitors of platelet aggregation, such as endothelium-derived relaxing factor (EDRF) and prostacyclin. With severe reductions in coronary blood flow caused by these mechanisms, platelet aggregates may increase, and an occlusive thrombus composed of platelets and white and red blood cells in a fibrin mesh may develop. When coronary arteries are occluded or narrowed for a sufficient period of time by these mechanisms, myocardial necrosis, electrical instability, or sudden death may occur. We believe that unstable angina and acute myocardial infarction are a continuum in relation to the process of coronary artery thrombosis and vasoconstriction. When the period of platelet aggregation or dynamic vasoconstriction at sites of endothelial injury and coronary artery stenosis is brief, unstable angina or non-Q wave infarction may occur. However, when the coronary artery obstruction by these mechanisms is prolonged for several hours, Q wave myocardial infarction results. Chronic endothelial injury and coronary artery stenosis are probably associated with the accumulation of platelets, white and red blood cells, and a fibrin mesh at the site of stenosis and endothelial injury.
Precipitating antigen-antibody systems are required for the formation of subepithelial electron-dense immune deposits in rat glomeruli.
Authors: L Y Agodoa, V J Gauthier, M Mannik
Journal: The Journal of Experimental Medicine (1983)

This study was conducted to determine whether multivalent, precipitating antigens are required for formation of subepithelial electron-dense immune deposits in glomeruli. 2-nitro-4-azidophenyl (NAP) was conjugated with variable density to human serum albumin (HSA) to yield nonprecipitating (NAP3.1 X HSA and NAP11.4 X HSA) and precipitating (NAP19.7 X HSA) antigens with antibodies to the hapten. These antigen preparations were cationized with ethylene diamine to enhance deposition in renal glomeruli due to interaction with the fixed negative charges in the glomerular capillary wall. Following injection into the left renal artery of rats these antigens alone persisted in the glomeruli for a relatively short time by immunofluorescence microscopy. When antibodies to NAP were injected intravenously after the antigen injection, the nonprecipitating antigens and antibodies were detectable in the glomeruli by immunofluorescence microscopy up to 8 h, comparable to antigen alone. Electron-dense deposits were not formed in these glomeruli. In contrast, when the precipitating antigen was injected and followed by antibodies to the hapten, antigen and antibody were detected by immunofluorescence microscopy through 96 h. In these specimens electron-dense deposits were present from 40 min through 96 h and after 24 h the deposits were present only in the subepithelial area. The same results were obtained when the nonprecipitating hapten-carrier conjugates were followed with antibodies to the carrier molecule. These data indicate that the persistence of immune deposits by immunofluorescence microscopy and the formation of electron-dense deposits in the subepithelial area require a precipitating antigen-antibody system.