tbuckley/cabot-search huggingface dataset:
Bile acid structure and selective modulation of murine hepatic cytochrome P450-linked enzymes
Authors: Moreno Paolini, Laura Pozzetti, Francesco Piazza, Giorgio Cantelli-Forti, Aldo Roda
Journal: Hepatology (1999)

We examined the effects of the administration of different bile acids on in vivo hepatic murine cytochrome P450 (CYP) content, nicotinamide adenine dinucleotide phosphate (NADPH)-CYP-reductase, and individual mixed-function oxidases (MFOs). Neither CYP level nor reductase were appreciably affected by single intraperitoneal administration of taurodeoxycholic acid (TDCA) (12.2 or 24.4 mg x kg(-1) bw). MFO to various isoenzymes were slightly reduced 24 hours after treatment. Taurohyodeoxycholic acid (THDCA) and tauroursodeoxycholic acid (TUDCA) both induced CYP, reductase, and MFOs. CYP3A1/2-linked activity (i.e., testosterone 6beta-hydroxylase, and N-demethylation of aminopyrine) in a dose-dependent fashion was enhanced ( approximately 2-3-fold). CYP2E1- (hydroxylation of p-nitrophenol), CYP1A2-(O-demethylation of methoxyresorufin), CYP2A1/2- and CYP2B1/2-(6alpha-hydroxylase), and CYP2B9- (16alpha-hydroxylase) dependent MFOs, as well as 7alpha-, 16beta-, 2alpha-, and 2beta-hydroxylations, were all significantly induced by THDCA. Apart from alkoxyresorufin metabolism and a modest CYP2E1 increase, TUDCA behaved like THDCA. A generalized induction was also recorded after ursodeoxycholic acid (UDCA) administration. THDCA and TDCA did not show substantial differences in the N-demethylation of aminopyrine when different species (rat vs. mouse) and administration route (intraperitoneal vs. intravenous) were compared. Results on the most affected isoenzymes, CYP3A1/2 (THDCA, TUDCA, and UDCA) and CYP2E1 (UDCA), were sustained by means of Western immunoblotting. CYP3A induction was paralleled by a corresponding increase in mRNA. These data could partially explain the therapeutic mechanism of UDCA, TUDCA, and THDCA in chronic cholestatic liver disease. CYP3A induction, which is linked to P-glycoprotein (Pgp) family overexpression, may enhance hepatic metabolism, transport, and excretion of toxic endogenous lipophilic bile acids.
Points from Letters: Treatment of Trigeminal Neuralgia
Authors: A. W. Galbraith
Journal: BMJ (1972)

isotopes could ethically be given.All three patients were able to form 25-hydroxycholecalciferol to the same extent as non- Pakistani control patients with a similar de- gree of vitamin D deficiency.The two Pakistani patients were also shown to form the potent biologically active metabolite 1,25 dihydroxycholecalciferol.Details relating to one of these patients have been published.2We feel therefore that inability to produce the appropriate metabolites of vitamin D is not the explanation for the phenomena re- ported in both surveys.-We are, etc.,
Evaluation of the Quality of Medical Care
Authors: Osler L. Peterson
Journal: New England Journal of Medicine (1963)

ALMOST every thoughtful discussion of medical care includes some mention of its quality. Although this interest is widespread more serious attempts have been made to define and measure quality in the United States than elsewhere in the world. This may be because doctors in America take responsibility for patients under more varied circumstances than doctors elsewhere. For example, nonspecialists in the United States do about half the surgery, deliver most of the babies and are often responsible for the care of critically ill patients.1 In European medical practice, by contrast, surgery and obstetrics are largely performed by specialists, and critically . . .
955-58 Intracardiac Echocardiographic Quantification and Monitoring of Myocardial Perfusion Defects and Reperfusion with the Use of Intravenous Injection of FS069, a Transpulmonic Contrast Agent
Authors: Steven Schwartz, Qi-Ling Cao, Alain Delabays, Lissa Sugeng, Natesa Pandian
Journal: Journal of the American College of Cardiology (1995)
Impact of Bone and Liver Metastases on Patients with Renal Cell Carcinoma Treated with Targeted Therapy
Authors: Rana R. McKay, Nils Kroeger, Wanling Xie, Jae-Lyun Lee, Jennifer J. Knox, Georg A. Bjarnason, Mary J. MacKenzie, Lori Wood, Sandy Srinivas, Ulka N. Vaishampayan, Sun-Young Rha, Sumanta K. Pal, Frede Donskov, Srinivas K. Tantravahi, Brian I. Rini, Daniel Y.C. Heng, Toni K. Choueiri
Journal: European Urology (2013)
ESTABLISHING SUCCESS OF THE HYOROXYAPATITE ORBITAL IMPLANT USING BONE SCINTIGRAPHY
Authors: C. Mazac, R. Dhekne, D. Pincus, H. Hintz-Hittner, S. Biondo, J. Blythe, W. Moore, P. Ford
Journal: Clinical Nuclear Medicine (1993)

Mazac, C.; Dhekne, R.; Pincus, D.; Hintz-Hittner, H.; Biondo, S.; Blythe, J.; Moore, W.; Ford, P. Author Information
Gene frequencies of human platelet alloantigens in Bahraini Arabs
Authors: Abeer M. Al‐Subaie, Iman K. Al‐Absi, Khadija Al‐Ola, Sarra Saidi, Naglaa A. Fawaz, Wassim Y. Almawi
Journal: American Journal of Hematology (2006)

Human platelet antigens (HPA) are implicated in the pathophysiology of certain hematological disorders, and as varied distribution of HPA-1 alleles and genotypes were reported fordifferent countries and ethnic populations, we determined the distribution of HPA-1, -2, -3, -4, and -5 alleles, genotypes and haplotypes for 194 healthy Bahraini subjects by polymerase chain reaction with sequence specific primers. The distribution of the HPA polymorphisms was in Hardy-Weinberg equilibrium. Allele frequencies of 0.76 and 0.24 (HPA-1a and -1b), 0.77 and 0.23 (HPA-2a and -2b), 0.57 and 0.43 (HPA-3a and -3b), 0.93 and 0.07 (HPA-4a and -4b), and 0.86 and 0.13 (HPA-5a and -5b) were seen. With the exception of HPA-3a/a (30.4%), the frequencies of homozygous HPA-1a/a (56.8%), 2a/a (60.1%), 4a/a (87.2%), and 5a/a (75.7%) were higher than those of heterozygous (a/b) or homozygous (b/b) variants. Our results provide basic information for further studies of the HPA system polymorphism, which in turn will be instrumental in understanding and treating immune-mediated platelet disorders.
Drug Treatment of Acute Asthma
Authors: Archie F. Wilson
Journal: JAMA (1977)

IN RECENT years, a number of effective regimens for the treatment of acute asthma in both children<sup>1</sup>and adults<sup>2</sup>have been devised. If there is one system that is clearly superior, such is not evident either from the literature or from my experience. Hence, in addition to a basic regimen, alternate or additional forms of therapy are outlined. Probably, the amount of drugs used early in the course of acute asthma and for a period extending beyond the acute stage is more important than choosing between several drugs. Also, since the severity of asthma may suddenly improve or worsen, it is necessary to frequently monitor the patient's condition and to assess the effects of treatment. It has been shown that a greater likelihood of prolonged treatment, indicating a need for hospitalization, is found in patients who suffer from severe obstruction and respond minimally to initial therapy.<sup>3</sup> <h3>Initial</h3>
The Effect of Prolonged Sodium Depletion and of Hydrallazine Hydrochloride and Hexamethonium Bromide on the Digital Vascular Resistance in Primary Hypertension
Authors: GERALD H. EURMAN, MILTON MENDLOWITZ
Journal: Circulation (1954)

The effect of dietary sodium depletion and of oral hydrallazine hydrochloride and parenteral hexamethonium bromide on the digital circulation was studied by repeated measurements of pressure and flow before and after inhibition of sympathetic nerve discharge in a small series of hypertensive patients. Sodium depletion had no demonstrable effect on neurogenic digital vasoconstriction but produced either a decrease in intrinsic digital vascular resistance, a decrease in intrinsic flow, or both. The chief effect of the drugs studied, in contrast, was elimination of neurogenic digital vasoconstriction.
[594] GSK625433; A NOVEL AND HIGHLY POTENT INHIBITOR OF THE HCV NS5B POLYMERASE
Authors: F. Gray, E. Amphlett, H. Bright, L. Chambers, A. Cheasty, R. Fenwick, D. Haigh, D. Hartley, P. Howes, R. Jarvest, F. Mirzai, F. Nerozzi, N. Parry, M. Slater, S. Smith, P. Thommes, C. Wilkinson, E. Williams
Journal: Journal of Hepatology (2007)
Increased concentrations of soluble interleukin-2 receptor in the serum of patients with systemic sclerosis.
Authors: P Airo, M Bettinzioli, R Gorla, R Cattaneo
Journal: Annals of the Rheumatic Diseases (1991)

Systemic sclerosis and porphyria cutanea tardaSir: The appearance of sclerodermoid changes in porphyria cutanea tarda is well known'; cases of porphyria cutanea tarda associated with systemic sclerosis have rarely been described, however.2 3 A further case of this association is reported here.Repeated phlebotomy led to a slight improvement in the cutaneous sclerosis, but visceral involvement remained unchanged.A 48 year old man was admitted for study of generalised cutaneous thickening.He was a heavy smoker and drinker.He had received no drugs and had not been in contact with toxic products.Outbreaks of vesicular lesions on the back of his hands, face, soles of the feet and intermittent dark urine had been evident for the past three years.Generalised skin thickening, particularly on his hands, and Raynaud's phenomenon had developed nine months before admission.Other clinical data included constitutional symptoms, pyrosis, impotence coeundi of six months' duration, and diffuse cutaneous hyperpigmentation last- ing for three months' before admission.Physical examination showed erosions, crusts, scars, and milium cysts in areas exposed to the sun and on the soles of his feet.There was diffuse hyperpigmentation with vitiligo-like patches.Skin thickening on the chest, back, abdomen, face, and arms made pinching impossible and greatly limited articular function.The legs were relatively unaffected.The finger tip showed pitting scars.There were no telangiectasias or sub- cutaneous calcifications.The remainder of the physical examination, blood and urine analy- sis were unremarkable.a Fetoprotein, car- cinoembryonic antigen, cortisol, and adreno- corticotrophic hormone were normal; iron 10 Imol/l (normal 10-28 psmol/l), transferrin
PTU-246 NHS bowel cancer screening programme
Authors: L Coleman, J Patnick, C Nickerson, H Griffiths, I Fretwell
Journal: Gut (2012)

<h3>Introduction</h3> <b>Background</b>: The NHS Bowel Cancer Screening Programme (BCSP) in England was established following successful pilot screening programmes in England and Scotland.<sup>1</sup> The BCSPcommenced in 2006 with a 3-year phased implementation offering screening to men and women aged 60–69. The programme also enabled people aged 70 and over to self-refer into the screening programme. <b>Objectives</b>: –reduce mortality from bowel cancer by up to 16%.<sup>2</sup> –offer men and women aged 60–69 a guaiac-based FOBt every 2 years. –enable those over 70 to be screened on request. –offer those with an abnormal screening result a colonoscopy as the investigation of choice. –refer for treatment if cancer is found at screening colonoscopy. –transfer to colonoscopic surveillance within BCSP where intermediate/high risk polyps are found. <h3>Methods</h3> The programme comprises five regional programme hubs responsible for call and recall, laboratory processing of test kits and booking clinic appointments for participants with abnormal FOBt results. Participants with an abnormal FOBt result are referred to a local screening centre to discuss colonoscopy with a specialist screening practitioner (SSP) within 2 weeks and offered a screening colonoscopy within a further 2 weeks. General practitioners are not directly involved in the screening process, but do receive information to support their patients to make an informed choice. <h3>Results</h3> All 58 screening centres have completed their prevalent round of screening, and the entire eligible population has received at least one invitation. The screening invitation age range is being extended to 75th birthday from 2010 in response to the government9s Cancer Reform Strategy. <h3>Conclusion</h3> Over twelve million invitations have been despatched. Data shows that uptake has increased from 47.73% in prevalent round to 87.41% in incident round and positivity has decreased from 2.19% in prevalent to 1.99% in incident round. Of these patients, prevalent round data showed 9.90% had a confirmed cancer diagnosis and in incident round this has reduced to 6.05%. Over 143 000 diagnostic tests have been carried out, of which 130 402 were screening colonoscopies. Episode outcomes also show a reduction in incident rounds of high risk polyps (10.21% to 7.65%) and intermediate risk polyps (17.95% to 14.33%). There has been an increase in low risk polyps (15.81% to 21.13%) and abnormal findings, not polyps (19.73% to 26.38%). <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Alexander F</b>, Weller D. <i>Evaluation of the UK Colorectal Cancer Screening Pilot</i>. Final Report, February 2003, revised May 2003. Report to The UK CRC Screening Pilot Evaluation Team. 2. <b>Cancer Research UK</b>. <i>UK Bowel Cancer Statistics</i>. http://info.cancerresearchuk.org/cancerstats
The Salmonella Kinase SteC Targets the MAP Kinase MEK to Regulate the Host Actin Cytoskeleton
Authors: Charlotte Odendall, Nathalie Rolhion, Andreas Förster, John Poh, Douglas J. Lamont, Mei Liu, Paul S. Freemont, Andrew D. Catling, David W. Holden
Journal: Cell Host & Microbe (2012)

After host cell entry, Salmonella replicate in membrane-bound compartments, which accumulate a dense meshwork of F-actin through the kinase activity of the Salmonella SPI-2 type III secretion effector SteC. We find that SteC promotes actin cytoskeleton reorganization by activating a signaling pathway involving the MAP kinases MEK and ERK, myosin light chain kinase (MLCK) and Myosin IIB. Specifically, SteC phosphorylates MEK directly on serine 200 (S200), a previously unstudied phosphorylation site. S200 phosphorylation is predicted to displace a negative regulatory helix causing autophosphorylation on the known MEK activatory residues, S218 and S222. In support of this, substitution of S200 with alanine prevented phosphorylation on S218 and S222, and phosphomimetic mutations of S200 stimulated phosphorylation of these residues. Both steC-null and kinase-deficient mutant strains displayed enhanced replication in infected cells, suggesting that SteC manipulates the actin cytoskeleton to restrain bacterial growth, thereby regulating virulence.
The self-organizing consciousness entails additional intervening subsystems
Authors: Takashi Yamauchi
Journal: Behavioral and Brain Sciences (2002)

The self-organizing consciousness (SOC) is not sufficient to account for young children's ability to acquire complex rules and word-object mappings. First, the attention-association cycles suggested by the SOC are unlikely to happen because recurrence of particular stimulus properties usually disengages the attention of an observer. Second, “primitive processors” preinstalled in the system make the SOC unnecessarily complex.
Many pain clinics fail to offer multidisciplinary care, says audit
Authors: J. Wise
Journal: BMJ (2012)

Many pain clinics in England and Wales fall well below the minimum requirements for an effective multidisciplinary pain service, the first national pain audit has concluded.1

The audit was commissioned by the Health Quality Improvement Partnership in response to the chief medical officer for England’s report Pain: Breaking through the Barrier .2 The audit found high variation in patients’ access to multidisciplinary care—considered to be the essential requirement for specialist chronic pain services. Waiting times and access to key skills of multidisciplinary team members also varied considerably.

The three year study, carried out by the British Pain Society and the healthcare …
The Evolution of Clinical Methods in Medicine: Being the Fitz-Patrick Lectures Delivered at the Royal College of Physicians in 1960-61
Authors: Lester S. King
Journal: JAMA (1964)

Since present-day medicine rests so largely upon laboratory data, today's students find difficulty in imagining any other form of practice. Only the historical approach can place these "tests" into the correct perspective. The methods used by the physician to diagnose disease have varied greatly over the years, and, as Keele states, represent "logical application of contemporary knowledge," depending on contemporary science. The history of medicine and the history of science are closely intertwined. In four chapters Keele surveys the evolution of clinical methods. First he takes up medicine in various ancient civilizations. Clinical history-taking and straightforward observation were the only available rational methods (but physicians were by no means always rational). The brilliant achievements of Hippocrates, depending on careful observation and cautious generalizations, were the foundations of all subsequent advance. In a second section the author traces the quest for "significant physical signs," such as examination of the urine, pulse,
Moses Maimonides on the Causes of Symptoms
Authors: H. R. Rollin
Journal: BMJ (1975)

circumstances certain procedures are indi- cated.By itself it is an inadequate guide, but it should find a place in the library of any children's hospital.While there are many excellent parts, the book as a whole lacks cohesion and fails to convey the wholepatient approach, though many of the authors pay lip service to this ideal.
Retinoic acid receptor ? dominant negative form causes steatohepatitis and liver tumors in transgenic mice
Authors: Atsushi Yanagitani, Sadako Yamada, Sakiko Yasui, Takashi Shimomura, Rie Murai, Yoshiyuki Murawaki, Koichi Hashiguchi, Takamasa Kanbe, Toshiya Saeki, Miho Ichiba, Yoshitada Tanabe, Yoko Yoshida, Shin-ichi Morino, Akihiro Kurimasa, Nobumitsu Usuda, Hidetoshi Yamazaki, Takahiro Kunisada, Hisao Ito, Yoshikazu Murawaki, Goshi Shiota
Journal: Hepatology (2004)

Although attention has focused on the chemopreventive action of retinoic acid (RA) in hepatocarcinogenesis, the functional role of RA in the liver has yet to be clarified. To explore the role of RA in the liver, we developed transgenic mice expressing RA receptor (RAR) alpha- dominant negative form in hepatocytes using albumin promoter and enhancer. At 4 months of age, the RAR alpha- dominant negative form transgenic mice developed microvesicular steatosis and spotty focal necrosis. Mitochondrial beta-oxidation activity of fatty acids and expression of its related enzymes, including VLCAD, LCAD, and HCD, were down-regulated; on the other hand, peroxisomal beta-oxidation and its related enzymes, including AOX and BFE, were up-regulated. Expression of cytochrome p4504a10, cytochrome p4504a12, and cytochrome p4504a14 was increased, suggesting that omega-oxidation of fatty acids in microsomes was accelerated. In addition, formation of H2O2 and 8-hydroxy-2'-deoxyguanosine was increased. After 12 months of age, these mice developed hepatocellular carcinoma and adenoma of the liver. The incidence of tumor formation increased with age. Expression of beta-catenin and cyclin D1 was enhanced and the TCF-4/beta-catenin complex was increased, whereas the RAR alpha/ beta-catenin complex was decreased. Feeding on a high-RA diet reversed histological and biochemical abnormalities and inhibited the occurrence of liver tumors. These results suggest that hepatic loss of RA function leads to the development of steatohepatitis and liver tumors. In conclusion, RA plays an important role in preventing hepatocarcinogenesis in association with fatty acid metabolism and Wnt signaling.
DISTRIBUTION, INHERITANCE, AND PROPERTIES OF AN ANTIGEN, MUB1, AND ITS RELATION TO HEMOLYTIC COMPLEMENT
Authors: B. Cinader, S. Dubiski, A. C. Wardlaw
Journal: The Journal of Experimental Medicine (1964)

An antigen, MuB1, present in the sera of some mice, can elicit a precipitating antibody in certain other strains of mice. An antibody to the antigen MuB1 can also be elicited in rabbits. 99 strains and substrains of inbred mice were tested for the presence of MuB1; the antigen was found in the sera of 44 strains (61 per cent) and 14 DBA substrains (52 per cent). Evidence is presented indicating that mice lacking MuB1 do not make a modified antigen, corresponding to MuB1, but are genetically deficient in synthetic ability at this site. By reaction with antibody to MuB1 an antigen corresponding to MuB1 was found in 13 of the 15 orders of mammals, and in 63 of 85 mammalian species tested, including man and guinea pig. The quantity of the antigen MuB1 is always greater in the serum of male than in the serum of female mice. The concentration of MuB1 increases with age; this increase is more marked in male than in female mice. By means of backcross experiments it was shown that the inheritance of MuB1 is unifactorial, is independent of the inheritance of the gamma globulin allotype MuA2, and is qualitatively independent of the sex of the parents. The antigen MuB1 is found in the euglobulin fraction of serum; it loses its ability to precipitate with antibody after heating at 56 degrees C, but not after treatment with ammonia or hydrazine. By gel filtration, MuB1 is separated with a fraction containing molecules of molecular weight approximately 150,000. An empirical correlation was observed between the presence or absence of MuB1 in the sera from inbred mice and the presence or absence of hemolytic complement (Hc), as measured by a test using a high concentration of rabbit hemolysin. In backcross experiments also, a correlation between hemolytic complement and the presence of MuB1 was demonstrated. As with MuB1, male mice had a higher hemolytic complement level than females. The particular component of complement which may be identical with MuB1 has not been identified.
The Price Tag on Progress — Chemotherapy for Colorectal Cancer
Authors: Deborah Schrag
Journal: New England Journal of Medicine (2004)

From the 1960s until the mid-1990s, fluorouracil was the primary chemotherapeutic agent available for the treatment of colorectal cancer. During the past decade, the Food and Drug Administration (FDA) has approved five new drugs for metastatic colorectal cancer. Irinotecan (approved in 1996) and oxaliplatin (2002) are cytotoxic agents that interfere with DNA replication, and capecitabine (1998) is an oral formulation of fluorouracil. This spring, the monoclonal antibodies bevacizumab and cetuximab, targeting vascular endothelial growth factor and epithelial growth factor receptor, respectively, were approved by the FDA for use in conjunction with cytotoxic regimens.Better systemic therapy has considerably improved prognosis. . . .
Management in the N.H.S
Authors: T. F. Mackintosh
Journal: BMJ (1972)

Boerhaave9s syndrome or spontaneous oesophageal perforation, is a potentially lethal and frequently elusive medical condition which presents not only a diagnostic but also a therapeutic challenge. It is insufficiently considered in diagnostic hypotheses, yet may be confirmed or excluded by simple methods such as an erect chest film and a contrast study of the oesophagus. Errors in diagnosis are usually caused by unawareness of its varied and atypical presentations or failure to consider its possibility in acute cardiothoracic and upper gastrointestinal conditions. Early aggressive surgical intervention in the form of open and wide mediastinal and chest drainage, with or without oesophageal repair, resection or exclusion, offers the patient the best chance of survival against this otherwise invariably fatal event. Nonoperative therapy consisting of antibiotics, nil oral regimen, nasogastric tube suction, pleural drainage, H2 receptor blockers and either a feeding enterostomy or total parenteral nutrition, may also be appropriate in selected patients. It is probable that the condition is more common than is generally supposed. All clinicians need to be aware of this lethal disease, its frequently unusual presentations and the importance of early diagnosis.