tbuckley/cabot-search huggingface dataset:
A Patient With Pancreas Divisum, Recurrent Acute Pancreatitis, and Homozygosity for the Cystic Fibrosis Transmembrane Regulator–Associated Protein 5T Allele
Authors: Marco Montagnani, Salvatore Cazzato, Massimiliano Mutignani, Monica Cevenini, Elena Guidetti, Ido Ben Zvi, Rita Aldini, Giacomo Saraceni, Carlotta Cavoli, Paolo Garagnani, Simona Ferrari, Vilma Mantovani
Journal: Clinical Gastroenterology and Hepatology (2013)
Formulation and in vivo evaluation of sodium alendronate spray-dried microparticles intended for lung delivery
Authors: Letícia Cruz, Elias Fattal, Leandro Tasso, Gabrielle C. Freitas, Adriano B. Carregaro, Sílvia S. Guterres, Adriana R. Pohlmann, Nicolas Tsapis
Journal: Journal of Controlled Release (2011)
Study on pharmacokinetics and tissue distribution of the isocorydine derivative (AICD) in rats by HPLC-DAD method
Authors: Yali Chen, Qian Yan, Mei Zhong, Quanyi Zhao, Junxi Liu, Duolong Di, Jinxia Liu
Journal: Acta Pharmaceutica Sinica B (2015)

A simple and effective high-performance liquid chromatography with diode-array detection method coupled with a liquid-liquid extraction pretreatment has been developed for determining the pharmacokinetics and tissue distribution of a novel structurally modified derivative (8-acetamino-isocorydine) of isocorydine. According to the in vivo experiments data calculations by DAS 2.0 software, a two-compartment metabolic model was suitable for describing the pharmacokinetic of 8-acetamino-isocorydine in rats. 8-Acetamino-isocorydine was absorbed well after oral administration, and the absolute bioavailability was 76.5%. The half-life of 8-acetamino-isocorydine after intravenous and oral administration was 2.2 h and 2.0 h, respectively. In vivo, 8-acetamino-isocorydine was highly distributed in the lungs, kidney and liver; however, relatively little entered the brain, suggesting that 8-acetamino-isocorydine could not easily pass through the blood brain barrier. Our work describes the first characterization of the pharmacokinetic parameters and tissue distribution of 8-acetamino-isocorydine. The acquired data will provide useful information for the in vivo pharmacology of 8-acetamino-isocorydine, and can be applied to new drug research.
Genetic testing for melanoma
Authors: Richard Kefford, Julia Newton Bishop, Margaret Tucker, Brigitte Bressac-de Paillerets, Giovanna Bianchi-Scarrá, Wilma Bergman, Alisa Goldstein, Susana Puig, Rona Mackie, David Elder, Johan Hansson, Nicholas Hayward, David Hogg, Håkan Olsson
Journal: The Lancet Oncology (2002)
Induction of HL-60 differentiation by starvation for a single essential amino acid but not by protein synthesis inhibitors.
Authors: R B Pilz, G Van den Berghe, G R Boss
Journal: Journal of Clinical Investigation (1987)

Starvation for a single essential amino acid induced differentiation of the human promyelocytic leukemia line HL-60 into morphologically and functionally mature granulocytes. Differentiation occurred when protein synthesis was inhibited up to 90% but was not simply secondary to growth arrest or protein synthesis inhibition, because neither glucose starvation nor treatment with protein synthesis inhibitors induced differentiation. Induction of differentiation by an aminoacyl tRNA synthetase inhibitor and the effect of cycloheximide and puromycin on amino acid-starved cells suggested an important regulatory role of tRNA molecules during differentiation.
Linking education, research, and service in general practice
Authors: P. Wallace, S. Drage, N. Jackson
Journal: BMJ (1998)

<h3>Abstract</h3> Enterohemorrhagic <i>Escherichia coli</i> (EHEC) has two critical virulence factors – a type III secretion system (T3SS) and Shiga toxins (Stx) – that are required for the pathogen to colonize the intestine and cause diarrheal disease. Here, we carried out a genome-wide CRISPR/Cas9 loss-of-function screen to identify host loci that facilitate EHEC infection of intestinal epithelial cells. Many of the guide RNAs identified targeted loci known to be associated with sphingolipid biosynthesis, particularly for production of globotriaosylceramide (Gb3), the Stx receptor. Two loci (TM9SF2 and LAPTM4A) with largely unknown functions were also targeted. Mutations in these loci not only rescued cells from Stx-mediated cell death, but also prevented cytotoxicity associated with the EHEC T3SS. These mutations interfered with early events associated with T3SS and Stx pathogenicity, markedly reducing entry of T3SS effectors into host cells and binding of Stx. The convergence of Stx and T3SS onto overlapping host targets provides guidance for design of new host-directed therapeutic agents to counter EHEC infection. <h3>Importance</h3> Enterohemorrhagic <i>Escherichia coli</i> (EHEC) has two critical virulence factors – a type III secretion system (T3SS) and Shiga toxins (Stx) – that are required for colonizing the intestine and causing diarrheal disease. We screened a genome-wide collection of CRISPR mutants derived from intestinal epithelial cells and identified mutants with enhanced survival following EHEC infection. Many had mutations that disrupted synthesis of a subset of lipids (sphingolipids) that includes the Stx receptor globotriaosylceramide (Gb3), and hence protect against Stx intoxication. Unexpectedly, we found that sphingolipids also mediate early events associated with T3SS pathogenicity. Since antibiotics are contraindicated for the treatment of EHEC, therapeutics targeting sphingolipid biosynthesis are a promising alternative, as they could provide protection against both of the pathogen’s key virulence factors.
SHOULD THE NUMBER OF PROFESSIONAL STUDENTS BE RESTRICTED?
Authors: RAYMOND WALTERS
Journal: JAMA (1935)

Should the number of professional students be restricted? This is no medieval, metaphysical question. It is as real as fresh paint on a front door, as timely as today's newspaper, as uncertain as anything that may happen tomorrow.  The question may be approached from three angles. One may approach it from the angle of personal interest. To do so is not necessarily to be selfish. For those of middle age or beyond, the answer is not of immediate concern, for whatever happens they can somehow wag along. Their personal interest is likely to center in the careers of their children and of young friends and students who come to them for counsel.  One may approach the question from the angle of professional interest. Proud of the past of the profession, imbued with its ethics and its spirit, one may honorably argue for its maintenance as it has been built up
Bone marrow and blood plasma levels of IL‐8 in aplastic anemia and their relationship with disease severity
Authors: Naresh Kumar Tripathy, None Vibhuti, Soniya Nityanand
Journal: American Journal of Hematology (2005)

Abstract Interleukin‐8 (IL‐8), a CXC chemokine, is also a potent inhibitor of myelopoiesis, the hematopoietic process that is severely impaired in aplastic anemia (AA). To elucidate its role in the disease, we have investigated levels of IL‐8 by quantitative enzyme‐linked immunosorbent assay in bone marrow and peripheral blood plasma of 27 AA patients and in the marrow of 16 controls and blood of 20 controls. Significantly increased levels of IL‐8 were observed in the marrow and blood of patients as compared to controls (470.4 ± 549.6 vs. 37.5 ± 30.3; P &lt; 0.0001) and (247.3 ± 286.3 vs. 7.9 ± 5.5; P &lt; 0.0001), respectively. Among the patients, the IL‐8 levels were higher in patients with severe AA than those with nonsevere AA in the marrow (568.8 ± 586.9 vs. 126.3 ± 102.5; P &lt; 0.005) as well as in the blood (296.6 ± 305.5 vs. 75.0 ± 84.4; P &lt; 0.008) plasma. The marrow and blood of 74% (20/27) of the patients had increased levels of IL‐8 compared to 12% (2/16; P &lt; 0.001) and 10% (2/20, P &lt; 0.001) of the controls, respectively. These results suggest that IL‐8 may have an important role in the pathogenesis of AA. Am. J. Hematol. 79:240–242, 2005. © 2005 Wiley‐Liss, Inc.
Influence of zoledronic acid on disseminated tumor cells (DTC) in primary breast cancer patients.
Authors: E Solomayer, G Gebauer, P Hirnle, W Janni, H Lück, S Becker, J Huober, B Kraemer, B Wackwitz, T Fehm
Journal: Cancer Research (2009)

Abstract Abstract #2048 Background: The presence of disseminated tumor cells (DTC) in the bone marrow is associated with an increased risk for subsequent bone metastases. Bisphosphonates reduce the occurence of bone metastases in patients (pts) with primary breast cancer (BC) with DTC. The aim of this trial was to evaluate the effect of adjuvant zoledronic acid (ZOL) on DTC in the bone marrow and the Patients and methods: Eligibilty criteria for this prospective, randomized multicenter trial were primary BC pts (pT1-4, N1-2, M0) with positive bone marrow status as determined by a standardized immunocytochemistry staining procedure. Ninety-eight pts were enrolled between April 2002 and January 2006. Randomization and medication had to be started within 28 days of primary surgery. Consenting pts were randomized to the treatment arm (ZOL 4mg i.v. q 4 weekly) or control arm. During the study, all pts received adjuvant treatment in the form of chemotherapy ± hormonal therapy or hormonal therapy alone. Bone marrow aspirations were performed to analyze the presence of DTC at surgery (baseline) and 12 months later. Efficacy and tolerability of intravenous ZOL in pts with primary Result: Bone marrow status was available for 76 patients both at baseline and 12 months after surgery. At baseline a median of 2.0 / range 1-6 (mean 2.1±1.1) DTC were detected in the ZOL group and a median of 2.0 / range 1-35 (mean 2.9±5.5) DTC in the control group. In both groups the number of detected tumor cells decreased during the 12 months follow-up with 0.5±0.8 (median 0.0; 0-2) DTC in the ZOL group and 0.9±0.8 (median 1.0; 0-2) DTC in the control group. By ANCOVA analysis a trend was seen towards a reduction of the number of DTC in the ZOL group compared with the control group (p=0.066). In addition, bone marrow-positive pts treated with ZOL were more likely to become bone marrow negative after 12 months (66.7% versus 35.1%, (p=0.009) compared to the control group. Most frequently reported AEs were musculoskeletal,arthralgia and myalgia in Conclusions: In this first prospective, randomized, multicenter trial we were able to show, that both treatment groups have a reduction in the number of DTC after 12 months as compared to baseline. There is a tendency to more reduction of DTC in the ZOL group. More pts under ZOL achieved a change from positive to negative bone marrow status than controls (p=0.009). Treatment with ZOL was safe and well tolerated. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2048.
A novel epitope on the C-terminus of SmD1 is recognized by the majority of sera from patients with systemic lupus erythematosus.
Authors: G Riemekasten, J Marell, G Trebeljahr, R Klein, G Hausdorf, T Häupl, J Schneider-Mergener, G R Burmester, F Hiepe
Journal: Journal of Clinical Investigation (1998)

The SmD1 protein is a specific target for the autoantibody response in SLE. To further analyze this reactivity epitope, mapping was performed with cellulose-bound 13-mer peptides overlapping 10 amino acids (aa). In this initial approach, 4 out of 15 SLE sera recognized more than five overlapping peptides of the SmD1 C-terminus. Therefore, longer oligopeptides of up to 37 aa of this region were generated and probed for as antigens by ELISA. For the SmD1 aa 83-119 polypeptide, there was a striking increase of reactivity with 70.0% positive reactions out of 167 SLE sera. In contrast, 105 healthy control sera were negative, and only 8.3% of sera from patients with other inflammatory diseases (n = 267) exhibited a response, which was of low level only. The anti-SmD183-119 reactivity was significantly higher in anti-dsDNA antibody positive vs. negative sera (P < 0.001) and correlated with disease activity. Four of five human monoclonal anti-dsDNA antibodies also reacted with SmD183-119. The specificity for SmD1 was demonstrated by inhibition experiments and immunization of rabbits with SmD183-119 inducing SmD1-specific antibodies. In conclusion, the SmD183-119 peptide was demonstrated to be an important and highly specific target of the autoimmune response in SLE. The high sensitivity of this ELISA probably depends on a conformational epitope, which appears not to be accessible in the full-size SmD1 protein.
States Face Rocky Road to Reform
Authors: Rebecca Voelker
Journal: JAMA (1995)

WHEN NATIONAL health system reform withered and died last September, state governments took center stage. Their reputations as "laboratories" for innovation and creativity grew, as the nation soon realized that reforms would be incremental rather than comprehensive. There's no doubt that the states will proceed with reform efforts in 1995. But many of the results—or lack thereof— will carry the imprint of two main elements in the states' formula for reform: waivers from the federal Health Care Financing Administration (HCFA) that allow state experimentation with Medicaid programs and the Employee Retirement Income Security Act of 1974 (ERISA) that governs employee benefit plans. "Even though national reform didn't materialize, the important issues have not gone away. Now the states will be the pressure point, and we can be effective, particularly if we get cooperation from the federal government," says Pennsylvania State Sen Allyson Schwartz (D, Philadelphia). <h3>Medicaid Waivers</h3> One such avenue
Ethical Use of Cogniceuticals in the Militaries of Democratic Nations
Authors: Michael B. Russo, Michael V. Arnett, Maria L. Thomas, John A. Caldwell
Journal: The American Journal of Bioethics (2008)

Click to increase image sizeClick to decrease image size Disclaimer and acknowledgement: The views expressed in this commentary are those of the authors and do not reflect the official policy or position of the United States Department of the Army, Department of Defense, or the United States government. This commentary includes concepts modified from earlier presentations by Russo, Caldwell, and Thomas at the Human Factors and Ergonomics Society—Foundations of Augmented Cognition Annual meeting, October 2007.
ABC of monitoring drug therapy. Phenytoin.
Authors: J. K. Aronson, M. Hardman, D. J. Reynolds
Journal: BMJ (1992)

Phenytoin is an anticonvulsant whose main use is as a second line drug in treating generalised tonic-clonic seizures and sometimes other forms of epilepsy.It can be used either to treat patients in whom seizures have occurred or to prevent seizures in patients at risk (for example, after neurosurgery).~~~v ~~~~~Because of large individual variation in the disposition of phenytoin -patients taking the same dosage have up to a 50-fold difference in plasma .
Use of Urinary Cotinine to Estimate Exposure to Tobacco Smoke
Authors: Robert D. Barlow
Journal: JAMA (1988)

<h3>To the Editor.</h3> —Sepkovic and colleagues<sup>1</sup>report that the half-life of cotinine in nonsmokers is 2.7 times that in smokers and that this difference "precludes a direct extrapolation to 'cigarette equivalents of smoke uptake' from a single measurement of urinary cotinine."<sup>1,2</sup>This conclusion seems unjustified since, even if there is a difference, once the magnitude of the difference has been established this can be taken into account when estimating the relative exposures of smokers and nonsmokers to tobacco smoke. In addition, there appears to be an error such that the difference is less than 2.7-fold. While the report by Sepkovic et al<sup>1</sup>reports a mean half-life of 18.5 hours (n = 10) for smokers and 49.7 hours for nonsmokers (n = 4), yielding a ratio of 2.7, the data presented in the figure that accompanies the report show that the half-life is about 27 hours for the nonsmokers rather
Abstract 4986: Nuclear PRAS40 regulates the cellular response to nucleolar stress
Authors: Jonathan Joseph Havel, Zenggang Li, Haian Fu
Journal: Cancer Research (2012)

Abstract The Proline-rich Akt Substrate of 40kDA (PRAS40) has recently been identified as a binding partner and inhibitor of the mammalian Target of Rapamycin Complex 1 (mTORC1), a growth factor- and nutrient-sensitive kinase whose activity promotes protein synthesis and cell growth. Despite its inhibitory effect on mTORC1, PRAS40 has been shown to promote cell survival in rodent models of spinal cord injury and tumorigenesis. Importantly, PRAS40 levels have also been found to correlate with poor prognosis in lung cancer patients, an effect not readily explained by mTORC1 inhibition. Here we demonstrate that in addition to its known cytoplasmic role in inhibiting mTORC1, PRAS40 also actively shuttles to the nucleus, where it congregates at the periphery of nucleoli and exists in a high-molecular weight complex void of mTORC1 components. Through immunoprecipitation and mass spectrometry analyses we have begun to identify members of this nuclear PRAS40 complex. Furthermore, we demonstrate that PRAS40 overexpression attenuates Actinomycin D-mediated induction of nucleolar stress markers. These findings may help to explain the apparent pro-tumorigenic effects of PRAS40 and identify the PRAS40 nuclear complex as a potential target for anti-cancer drug discovery. 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 4986. doi:1538-7445.AM2012-4986
Annexin 1 expression and phosphorylation are upregulated during liver regeneration and transformation in antithrombin iii sv40 t large antigen transgenic mice
Authors: Catherine de Coupade, Raphaëlle Gillet, Myriam Bennoun, Pascale Briand, Françoise Russo-Marie, Egle Solito
Journal: Hepatology (2000)

We have used a transgenic animal model, which constitutively develops hepatocarcinoma (Antithrombin III SV40 T large Antigen: ASV), to study the involvement of Annexin 1 (ANX1) in liver regeneration and malignant transformation. Primary hepatocytes isolated from normal mice did not express ANX1. In contrast, ANX1 was strongly expressed in hepatocytes of transgenic mice during constitutive development of hepatocarcinoma. In ASV transgenic mice, an elevated ANX1 level preceded the appearance of the tumor, indicating that it could be a good marker in the diagnosis of cancer. One-third hepatectomy in normal mice resulted in stimulation of ANX1 synthesis and phosphorylation. This upregulation correlated with increased synthesis of EGF and consequently with increased phosphorylation of the EGF receptor (EGF-R). Stable transfection of a hepatocyte cell line derived from ASV transgenic mice (mhAT2) with antisense complementary DNA for ANX1 reduced the proliferation rate as well as cytosolic phospholipase A 2 (cPLA 2 ) activity. Thus, ANX1 expression and phosphorylation could be a factor implicated in liver regeneration and tumorigenesis, either through modulation of cPLA 2 activity or EGF-R function.
Absence of Association or Genetic Linkage between the Angiotensin-Converting–Enzyme Gene and Left Ventricular Mass
Authors: Klaus Lindpaintner, MinAe Lee, Martin G. Larson, V. Srinivas Rao, Marc A. Pfeffer, Jose M. Ordovas, Ernst J. Schaefer, Alexander F. Wilson, Peter W.F. Wilson, Ramachandran S. Vasan, Richard H. Myers, Daniel Levy
Journal: New England Journal of Medicine (1996)

Background Homozygous carriers of the D allele of the angiotensin-converting–enzyme (ACE) gene have been reported to be at increased risk for various cardiovascular disorders, including left ventricular hypertrophy. We investigated the potential role of the ACE gene in influencing left ventricular mass. Methods Quantitative echocardiographic data and DNA samples were available for 2439 subjects from the Framingham Heart Study. ACE genotypes were determined by an assay based on the polymerase chain reaction. (The D allele of the ACE gene contains a deletion, whereas the I [insertion] allele does not.) Left ventricular mass and the prevalence of left ventricular hypertrophy, adjusted for clinical covariates, were analyzed according to genotype. Genetic linkage between the ACE locus and left ventricular mass was evaluated by quantitative analysis of pairs of siblings. Results The ACE genotype was associated neither with left ventricular mass nor with the prevalence of left ventricular hypertrophy. Mean (±SE)...
1101-63 Impact of preinterventional lesion calcification on neointimal hyperplasia following sirolimus-eluting stent implantation: An intravascular ultrasound analysis
Authors: Hideaki Kaneda, Tomomi Koizumi, Junya Ako, Yasuhiro Honda, Mitsuyasu Terashima, Yoshihisa Shimada, Yoshihiro Morino, Paul G Yock, Martin B Leon, Jeffrey W Moses, Peter J Fitzgerald
Journal: Journal of the American College of Cardiology (2004)
Intra-group Transfusion Reactions
Authors: K. S. Ranganathan
Journal: BMJ (1947)

and in the case of the younger men the financial penalties imposed on them if they resign before the end of the three years' probationary service are too great for their slender resources.Those who intend joining the service must know that there is grave discontent among, medical officers in Malaya and that this discontent is amply justified.They must also realize that they can place no trust in the truth of statements concerning conditions of service in the Colonies made to them at their interview in London.These are not the complaints of an inexperienced person who takes badly to service conditions, for I have already had six years with the Navy and am well used to the discipline of that Service.Nor are they those of one who dislikes hard work in a hospital.They are, the bitter -complaints of a man who resigned after six months in the Malayan Medical Service and who has seen his plans for the future destroyed by the deliberate misrepresentations of a supposedly responsible Government Department.-Iam, etc., Singapore.
Spinal Bracing in Adolescent Idiopathic Scoliosis
Authors: Eugene J. Carragee, Ronald A. Lehman
Journal: New England Journal of Medicine (2013)

Before the introduction of the poliomyelitis vaccination, paralysis due to poliovirus infection was a leading cause of spinal deformity in children and young adults. The severe, stiff spinal deformities associated with poliovirus infection were complicated by pulmonary dysfunction; spinal bracing, which was often ineffective in correcting the deformity or preventing the progression of scoliosis, also exacerbated restrictive pulmonary disease, pulmonary hypertension, and cor pulmonale. Today, coronal spinal deformity in children and young adults is nearly always adolescent idiopathic scoliosis: a flexible, three-dimensional, spinal curvature affecting primarily girls, beginning in adolescence, and very rarely leading to clinically significant cardiopulmonary disease. When . . .
Monitoring of respiratory variations of aortic blood flow velocity using esophageal Doppler
Authors: Michel Slama, Henri Masson, Jean-Louis Teboul, Marie-Luce Arnould, Rachida Nait-Kaoudjt, Bouchra Colas, Marcel Peltier, Christophe Tribouilloy, Dinko Susic, Edward Frohlich, Michel Andréjak
Journal: Intensive Care Medicine (2004)