tbuckley/cabot-search huggingface dataset:
Telomere shortening and inactivation of cell cycle checkpoints characterize human hepatocarcinogenesis
Authors: Ruben Raphael Plentz, Young Nyun Park, André Lechel, Haeryoung Kim, Friederike Nellessen, Britta Heike Eva Langkopf, Ludwig Wilkens, Annarita Destro, Barbara Fiamengo, Michael Peter Manns, Massimo Roncalli, Karl Lenhard Rudolph
Journal: Hepatology (2007)

Telomere shortening and inactivation of cell cycle checkpoints characterize carcinogenesis. Whether these molecular features coincide at specific stages of human hepatocarcinogenesis is unknown. The preneoplasia–carcinoma sequence of human HCC is not well defined. Small cell changes (SCC) and large cell changes (LCC) are potential precursor lesions. We analyzed hepatocellular telomere length, the prevalence of DNA damage, and the expression of p21 and p16 in biopsy specimens of patients with chronic liver disease (n = 27) that showed different precursor lesions and/or HCC: liver cirrhosis (n = 25), LCC (n = 26), SCC (n = 13), and HCC (n = 13). The study shows a decrease in telomere length in nondysplastic cirrhotic liver compared with normal liver and a further significant shortening of telomeres in LCC, SCC, and HCC. HCC had the shortest telomeres, followed by SCC and LCC. Hepatocytes showed an increased p21 labeling index (p21-LI) at the cirrhosis stage, which remained elevated in most LCC. In contrast, most SCC and HCC showed a strongly reduced p21-LI. Similarly, p16 was strongly expressed in LCC but reduced in SCC and not detectable in HCC. γH2AX-DNA-damage-foci were not detected in LCC but were present in SCC and more frequently in HCC. These data indicate that LCC and SCC represent clonal expansions of hepatocytes with shortened telomeres. Conclusion: The inactivation of cell cycle checkpoints coincides with further telomere shortening and an accumulation of DNA damage in SCC and HCC, suggesting that SCC represent more advanced precursor lesions compared with LCC. (HEPATOLOGY 2007;45:968–976.)
A Limited Role for Gene Duplications in the Evolution of Platypus Venom
Authors: E. S. W. Wong, A. T. Papenfuss, C. M. Whittington, W. C. Warren, K. Belov
Journal: Molecular Biology and Evolution (2011)

Gene duplication followed by adaptive selection is believed to be the primary driver of venom evolution. However, to date, no studies have evaluated the importance of gene duplications for venom evolution using a genomic approach. The availability of a sequenced genome and a venom gland transcriptome for the enigmatic platypus provides a unique opportunity to explore the role that gene duplication plays in venom evolution. Here, we identify gene duplication events and correlate them with expressed transcripts in an in-season venom gland. Gene duplicates (1,508) were identified. These duplicated pairs (421), including genes that have undergone multiple rounds of gene duplications, were expressed in the venom gland. The majority of these genes are involved in metabolism and protein synthesis not toxin functions. Twelve secretory genes including serine proteases, metalloproteinases, and protease inhibitors likely to produce symptoms of envenomation such as vasodilation and pain were detected. Only 16 of 107 platypus genes with high similarity to known toxins evolved through gene duplication. Platypus venom C-type natriuretic peptides and nerve growth factor do not possess lineage-specific gene duplicates. Extensive duplications, believed to increase the potency of toxic content and promote toxin diversification, were not found. This is the first study to take a genome-wide approach in order to examine the impact of gene duplication on venom evolution. Our findings support the idea that adaptive selection acts on gene duplicates to drive the independent evolution and functional diversification of similar venom genes in venomous species. However, gene duplications alone do not explain the "venome" of the platypus. Other mechanisms, such as alternative splicing and mutation, may be important in venom innovation.
Administration of vitamin K to newborn infants and childhood cancer.
Authors: H Ekelund, O Finnstrom, J Gunnarskog, B Kallen, Y Larsson
Journal: BMJ (1993)

To investigate whether childhood cancer is associated with intramuscular administration of vitamin K to newborn infants.Routines for administration of vitamin K to infants born after normal deliveries during 1973-89 were obtained from maternity hospitals. Occurrence of cancer up to the end of 1991 was identified by comparing these records with the national cancer registry. Adherence to the routine method of administering vitamin K was checked with the medical records of a sample of 396 infants (196 who had developed childhood cancer and 200 controls).All maternity hospitals in Sweden.1,384,424 full term infants born after non-instrumental deliveries, 1,085,654 of whom were born in units where vitamin K was routinely given by intramuscular injection and 272,080 of whom were born where it was given orally.Odds ratios for cancer after intramuscular administration of vitamin K versus oral administration after stratification for year of birth.Adherence to routine method of administering vitamin K was 92% in the 235 cases where individual information could be found. The risk of cancer after intramuscular administration of vitamin K was not elevated compared with that after oral administration: odds ratios of 1.01 (95% confidence interval 0.88 to 1.17) for all childhood cancers and 0.90 (0.70 to 1.16) for childhood leukaemia.The alleged association between intramuscular vitamin K prophylaxis to newborn infants and childhood cancer could not be verified in the present study of full term infants born after non-instrumental delivery.
Bovine immunoglobulin concentrate-<i>Clostridium difficile</i> retains <i>C difficile</i> toxin neutralising activity after passage through the human stomach and small intestine
Authors: M Warny, A Fatimi, E F Bostwick, D C Laine, F Lebel, J T LaMont, C Pothoulakis, C P Kelly
Journal: Gut (1999)

Background Bovine immunoglobulin concentrate (BIC)- Clostridium difficile is prepared from the colostrum of cows immunised against C difficile toxins and contains high concentrations of neutralising IgG antitoxin. Aims To determine the proportion of BIC- C difficile which survives passage through the human stomach and small intestine. Methods Six volunteers with an end ileostomy took 5 g of BIC- C difficile containing 2.1 g of bovine IgG on four occasions: alone, with an antacid, during treatment with omeprazole, and within enteric coated capsules. Results When BIC- C difficile was taken alone, a mean (SEM) of 1033 (232) mg of bovine IgG was recovered in the ileal fluid representing 49% of the total ingested dose. Bovine IgG recovery was not significantly increased by antacid (636 (129) mg) or omeprazole (1052 (268) mg). The enteric capsules frequently remained intact or only partially opened in the ileal effluent and free bovine IgG levels were low in this treatment group (89 (101) mg). Bovine IgG recovery was higher in volunteers with shorter (less than two hours) mouth to ileum transit times (68% versus 36%, p&lt;0.05). Specific bovine IgG against C difficile toxin A was detected in ileal fluid following oral BIC. Toxin neutralising activity was also present and correlated closely with bovine IgG levels ( r =0.95, p&lt;0.001). Conclusion BIC- C difficile resists digestion in the human upper gastrointestinal tract and specific anti- C difficile toxin A binding and neutralising activity was retained. Passive oral immunotherapy with anti- C difficile BIC may be a useful non-antibiotic approach to the prevention and treatment of C difficile antibiotic associated diarrhoea and colitis.
Public Opinion at the Time of the Vote on Health Care Reform
Authors: Robert J. Blendon, John M. Benson
Journal: New England Journal of Medicine (2010)

On March 23, 2010, President Barack Obama signed a major health care reform law, about which public opinion was generally reported to be sharply divided. We undertook a comprehensive review of findings from 33 independent polls conducted before and immediately after Congress voted on the legislation and the President signed it, in order to examine the state of public opinion at the time it was enacted and to explore the possible implications for public support over the course of its implementation phase (see Opinion Polls on Health Care Reform). Specifically, we examined the overall public support just before enactment; public . . .
Is bile acid malabsorption underdiagnosed? An evaluation of accuracy of diagnosis by measurement of SeHCAT retention.
Authors: M V Merrick, M A Eastwood, M J Ford
Journal: BMJ (1985)

The cause of intractable chronic diarrhoea was found to be malabsorption of bile acid in five out of 42 patients thought to have the irritable bowel syndrome, six out of 29 patients with persistent diarrhoea after surgery for peptic ulcer, 23 who had undergone small bowel resection, and two others. Specific treatment brought symptomatic relief. The diagnosis was established by measuring the proportion of SeHCAT, a synthetic bile salt, retained one week after oral administration of a tracer dose of less than 100 micrograms of the compound labelled with 40 kBq (1 microCi) of selenium-75. These results indicate that malabsorption of bile acid is a more common cause of chronic diarrhoea than is generally appreciated. Measurement of retention of SeHCAT is a simple, accurate, and acceptable means of establishing the diagnosis of this debilitating but treatable condition.
BERIBERI AND RICE NEURITIS
Authors: MATARO NAGAYO
Journal: JAMA (1923)

Problems concerning the study of beriberi in its relation to the experimental investigations in animals maintained on deficient diets still offer great interest. In Japan, where many cases of beriberi are encountered every year, the study of this disease, together with that of the nature of vitamins and avitaminosis, is carried on very diligently so that in every biannual meeting of the Beriberi Investigation Committee under the auspices of the Department of War we are made acquainted with numbers of new investigations, which are freely discussed from all sides. On account of our advantageous opportunity for the study of human beriberi in comparison with the so-called polished rice disease in experimental animals, a short report on the research work in Japan may be of some value. The results of these researches have appeared, however, in numerous publications extending over many years, so that it will be possible merely to summarize
Pseudotumor Cerebri Associated with Pernicious Anemia
Authors: Thomas E. Murphy, John J. Costanzi
Journal: Annals of Internal Medicine (1969)

A 22-year-old woman had a unique association of neurologic abnormalities and pernicious anemia. These neurological abnormalities consisted of headache, nausea, vomiting, and increased intracranial pressure associated with papilledema with diffuse and focal electroencephalographic changes. All of these signs and symptoms disappeared with vitamin B12 therapy. Early recognition of the pernicious anemia circumvented serious complications and prevented the performance of unnecessary and potentially hazardous diagnostic procedures.
Allergen reference doses for precautionary labeling (VITAL 2.0): Clinical implications
Authors: Katrina J. Allen, Benjamin C. Remington, Joseph L. Baumert, Rene W.R. Crevel, Geert F. Houben, Simon Brooke-Taylor, Astrid G. Kruizinga, Steve L. Taylor
Journal: Journal of Allergy and Clinical Immunology (2013)
1124-198 Plasma sphinomyelin levels in coronary artery disease: A relationship with serum triglyceride and apolipoprotein B and other risk factors
Authors: Axel Schlitt, Stefan Blankenberg, Daoguang Yan, Hans von Gyzicki, Christoph Bickel, Karl Lackner, Juergen Meyer, Hans J Rupprecht, Xian-Cheng Jiang
Journal: Journal of the American College of Cardiology (2004)
Proarrhythmic effects of antiarrhythmic drugs during programmed ventricular stimulation in patients without ventricular tachycardia
Authors: Phillip K. Au, Anil K. Bhandari, Randall Bream, Douglas Schreck, Rukhsana Siddiqi, Shahbudin H. Rahimtoola
Journal: Journal of the American College of Cardiology (1987)
Recent Advances in Computational Methods for Nuclear Magnetic Resonance Data Processing
Authors: Xin Gao
Journal: Genomics Proteomics & Bioinformatics (2013)

Abstract Although three-dimensional protein structure determination using nuclear magnetic resonance (NMR) spectroscopy is a computationally costly and tedious process that would benefit from advanced computational techniques, it has not garnered much research attention from specialists in bioinformatics and computational biology. In this paper, we review recent advances in computational methods for NMR protein structure determination. We summarize the advantages of and bottlenecks in the existing methods and outline some open problems in the field. We also discuss current trends in NMR technology development and suggest directions for research on future computational methods for NMR.
Rupture of Atheromatous Abdominal Aorta
Authors: C. Boroda
Journal: BMJ (1944)

Pathological Report.-"The tumour has a structure superficially resembling an adenomatous polyp but in many areas showing dis- orderliness suggestive of adenocarcinomatous transformation.The epithelial cells in many parts' are distinctly hyperchromatic and have an anaplastic appearance.In some areas the dema'rcation between epithelial cells and the supporting connective-tissue framework is disorderly, and there is in parts a heavy infiltration of inflammatory cells.On the whole the appearance is suggestive of a low degree of malignancy."* Case 2.-A girl aged 16, a shop-assistant and daughter of the above, was admitted to Llandough Hospital on Feb. 3, 1943, with a history of abdominal pain and vomiting for about 24 hours, the bowel action being normal.On examination the temperature was 100' and the pulse rate 126 a minute.There was marked tenderness around the umbilicus and in the right iliac fossa, but no mass was palpable.Immediate laparotomy was performed (D.B. E. F.); this revealed an ileo-ileal intussusceptioni.Reduction by the usual technique'was attempted, but the intussuscipiens then split for about 4 in.In view of this, enterectomy was performed and approximately 14 in. of gut was removed and continuity re-established by end-to-end anastomosis.Post-operative progress was satisfactory, and a year later she is symptomless.
100 Cases of Tumor Metastatic to Lung and Mediastinum
Authors: Rollin M. Johnson
Journal: JAMA (1967)

One hundred cases of metastasis to lung or mediastinum from an extrathoracic source were reviewed. Fifty-nine patients were considered inoperable following initial investigation, eight were unresectable at thoracotomy, and eight had palliative resections or resection prior to control of the primary. None of these survived beyond 26 months. Twenty-five patients had resections for cure, with a fiveand ten-year survival of 47% (9 of 19 survivors) and 25% (3 of 12 survivors), respectively. Criteria for selection included control of the primary lesion with metastases limited to one lung. Best results were obtained when pulmonary metastases were detected more than one year following control of the primary lesion. About 5% of all patients with visceral malignancy manifest a pulmonary metastasis which should meet these criteria. Resection is possible with a low operative mortality (3%) and a prognosis often better than with bronchogenic carcinoma.
Calcineurin in Human Heart Hypertrophy
Authors: Oliver Ritter, Susanne Hack, Kai Schuh, Nicola Röthlein, Andreas Perrot, Karl J. Osterziel, Hagen D. Schulte, Ludwig Neyses
Journal: Circulation (2002)

In animal models, increased signaling through the calcineurin pathway has been shown to be sufficient for the development of cardiac hypertrophy. Calcineurin activity has been reported to be elevated in the myocardium of patients with congestive heart failure. In contrast, few data are available about calcineurin activity in patients with pressure overload or cardiomyopathic hypertrophy who are not in cardiac failure.We investigated calcineurin activity and protein expression in 2 different forms of cardiac hypertrophy: hypertrophic obstructive cardiomyopathy (HOCM) and aortic stenosis (AS). We found that the C-terminus of calcineurin A protein containing the autoinhibitory domain was less abundant in myocardial hypertrophy than in normal heart, which suggests the possibility of proteolysis. No new splice variants could be detected by reverse-transcription polymerase chain reaction. This resulted in a significant elevation of calcineurin enzymatic activity in HOCM and AS compared with 6 normal hearts. Increased calcineurin phosphatase activity caused increased migration of NF-AT2 (nuclear factor of activated T cells 2) in SDS-PAGE compatible with pronounced NF-AT dephosphorylation in hypertrophied myocardial tissue.Hypertrophy in HOCM and AS without heart failure is characterized by a significant increase in calcineurin activity. This might occur by (partial) proteolysis of the calcineurin A C-terminus containing the autoinhibitory domain. Increased calcineurin activity has functional relevance, as shown by altered NF-AT phosphorylation state. Although hypertrophy in AS and HOCM may be initiated by different upstream triggers (internal versus external fiber overload), in both cases, there is activation of calcineurin, which suggests an involvement of this pathway in the pathogenesis of human cardiac hypertrophy.
The future of cancer registries
Authors: A Pollock
Journal: BMJ (1994)

The abolition of regional health authorities raises questions about the future of the 12 regional cancer registries in England and Wales. Their survival will now depend on their ability to persuade district health authorities that they are essential for purchasing. This in turn will depend on how quickly they can acquaint purchasers with their role and function.

Cancer registration was introduced by clinicians in the 1930s to evaluate new treatments such as radium therapy. It has come to be identified with narrowly epidemiological aims, yet most registries hold a wealth of data that are vital for evaluating health care - for example, on treatment, tumour stage, place of treatment, consultant, and place of death. Although notification is voluntary, the registries achieve over 90% ascertainment for most cancers.1 They contribute population data to the national cancer registration system at the Office of Population Censuses and Surveys, which in turn publishes annual statistics on incidence and mortality and, all too infrequently, survival.2

Most district purchasers use registry data only to monitor trends in incidence and mortality and to ensure that these accord with targets set out in the Health of the Nation. This is because many are ignorant about what registries can do; they know that many clinicians doubt the accuracy of registry data, and they may perceive that a registry duplicates data that they already collect. Since 1993 NHS acute hospital providers have had to make a return on …
Groups Promote “Key Competencies” in Training for Premed and Medical Students
Authors: Bridget M. Kuehn
Journal: JAMA (2009)

UNDERGRADUATE PREMEDICAL programs and medical schools should revamp their curricula to emphasize a set of “key competencies” that will help individuals become good physicians, according to a report issued by the Association of American Medical Colleges (AAMC) and the Howard Hughes Medical Institute (HHMI). The report, written by a committee of 22 scientists, physicians, and educators, outlines principles to help guide school administrators in implementing the approach (http://services.aamc.org /publications/showfi le .cfm?fi le =version132.pdf&prd_id=262&prv_id =321&pdf_id=132). It also recommends several competencies that premedical and medical students should master to acquire quantitative skills and the ability to apply knowledge of such areas as biochemistry, molecular biology, genetics, and systems biology to medicine. These recommendations are being considered by another AAMC committee reviewing the Medical College Admission Test. The review and recommendations on changes to the test are expected in 2012. A competency-based approach would allow undergraduate institutions greater freedom to design innovative programs and would give students more flexibility to pursue a well-rounded liberal arts education, according to theauthorsof the AAMC and HHMI report. The need for such innovation in undergraduate biology education was outlined in a 2003 National Research Council report BIO2010: Transforming Undergraduate Education forFutureResearchBiologists (http://www .nap.edu/catalog.php?record_id =10497). The report noted that undergraduate biology education has changed little over the past 2 decades despite rapid changes brought about by advances in genetics, research tools, and digital technologies. In light of these changes, biology students need stronger quantitative skills, more knowledge of physics and chemistry, better communication skills, and the ability think in interdisciplinary terms, the report argued.
An Epidemic of Suicide Among Physicians on Probation
Authors: Ralph Crawshaw
Journal: JAMA (1980)

IN 1976, the members of the Oregon Board of Medical Examiners grew uneasy with the incidence of suicide among the physicians they had placed under close examination and probation. Since its inception in 1889, the board has acted through its power of licensure as the primary force regulating the medical profession in the state of Oregon. The board is composed of eight members who represent a cross section of the geographic distribution of physicians in the state. Board members are generally appointed by the governor from a list, proposed by the Oregon Medical Association, of physicians who are recognized and respected in their communities. The disciplinary mode of the board is expressed in its powers of probation. When a physician in Oregon is found culpable of professional misconduct of sufficient weight to merit probation, his license to practice is suspended and immediately reinstated, generally for a probationary period of ten
Impact of Rituximab and/or High-Dose Therapy With Autotransplant at Time of Relapse in Patients With Follicular Lymphoma: A GELA Study
Authors: Catherine Sebban, Pauline Brice, Richard Delarue, Corinne Haioun, Bertrand Souleau, Nicolas Mounier, Nicole Brousse, Pierre Feugier, Hervé Tilly, Philippe Solal-Céligny, Bertrand Coiffier
Journal: Journal of Clinical Oncology (2008)

The treatment of patients with follicular lymphoma has changed with the introduction of high-dose therapy (HDT) with autologous stem-cell transplant then with rituximab. The effect of these two strategies on the outcome of relapsing patients with follicular lymphoma has never been compared.We analyzed two cohorts of patients treated in two successive randomized studies with the same treatment, cyclophosphamide, doxorubicin, teniposide, and prednisolone plus interferon, to evaluate the role of rituximab and HDT in salvage therapy after first disease progression or relapse.Of the 364 patients included in these two studies, 254 progressed or relapsed and constitute the population of this analysis. Among them, 98 had been treated with HDT, including 33 of them after rituximab-containing salvage regimen, and 69 with rituximab alone or combined with chemotherapy but without HDT. Patients' characteristics at diagnosis were similar in all subgroups. If event-free survival was identical for patients treated within Groupe d'Etude des Lymphomes Folliculaires (GELF) -86 or GELF-94 studies, overall survival was longer in GELF-94 study. HDT was associated with a statistically significant benefit in terms of event-free survival from relapse and survival after relapse (SAR). Rituximab was associated with a greater benefit than HDT for these two end points. When both treatments were combined, patients treated with rituximab-containing salvage regimen followed by HDT had 5-year SAR more than 90%.In follicular lymphoma, for patients treated with first-line chemotherapy the combination of a salvage regimen containing rituximab with or without HDT leads to a dramatic improvement of long-term outcome.