tbuckley/cabot-search huggingface dataset:
A Site-specific Measure for Rate Difference After Gene Duplication or Speciation
Authors: Xun Gu
Journal: Molecular Biology and Evolution (2001)

Gene family proliferation by gene (genome) duplication has provided the raw materials for functional innovations (Ohno 1970; Lundin 1993; Holland et al. 1994; Henikoff et al. 1997; Golding and Dean 1998). Several models were proposed for functional divergence among member genes (e.g., Li 1983; Clark 1994; Hughes 1994; Fryxell 1996; Nei, Gu, and Sitnikova 1997; Force et al. 1999), but the details remain largely unknown. Gu (1999) developed a statistical method for testing type I functional divergence, i.e., changes in protein function between two gene clusters result in changes in selective constraints (and therefore shifted evolutionary rates) at some residues. It stands in contrast to type II functional divergence, i.e., changes in protein function between two gene clusters do not alter the level of selective constraints. Amino acid residues with rate shifts are the sites that have either gained or lost importance as a consequence of the change of function during evolution, as proposed by the hypothesis of type I functional divergence (Gu 1999). Moreover, type I functional divergence provides a biological basis for the covarion theory of molecular evolution (Fitch and Markowitz 1970). If a statistical testing shows a significant rate difference between two gene clusters, it is of great interest to predict important amino acid residues, which can be further verified by available functional-structural evidence (Dermitzakis and Clark 2001; Gaucher, Miyamoto, and Benner 2001; Wang and Gu 2001). The posterior probability of each site is suitable to develop a statistically sound profile for selecting critical amino acid residues (Gu 1999), but little information is provided about how much rate difference is generated at these sites after gene duplication. In this article, we report a new site-specific profile for the rate difference, which is useful for studying the pattern of protein sequence evolution. Consider two gene clusters generated by gene duplication (or speciation), e.g., see figure 1, the bone morphogenetic proteins (BMP) gene family tree. In each cluster, a site can be in either of two states: (1) F0, which means no altered functional constraint after gene duplication, and (2) F1, which means altered functional constraint at this site after gene duplication. As a result, there are four combined states in the case of two gene clusters: (1) F0 in both clusters, denoted by S0 5 (F0, F0), resulting in no rate difference between clusters; and
Abstract 657: Perinatal factors and breast cancer risk: The CECILE study
Authors: Florence Menegaux, Antoinette Anger, Therese Truong, Pascal Guenel
Journal: Cancer Research (2012)

Abstract Objectives: Perinatal period and adolescence are key periods of breast cancer development with increased susceptibility to carcinogens. A high level of endogenous estrogens in utero was suggested as a possible risk factor for breast cancer in daughters. We investigated the role of perinatal factors in breast cancer in the CECILE study, a population-based case-control study. Methods: The CECILE study was conducted in two French départements (Côte d'Or, Ille-et-Vilaine) between 2005 and 2008. A total of 1232 incident breast cancer cases and 1317 population age-matched controls were included. An in-person interview was conducted using a standardized questionnaire to obtain information on recognized or suspected risk factors for breast cancer. A self-administered questionnaire was used to obtain information on perinatal factors and was returned by mail by 871 cases (71%) and 915 controls (69%). The perinatal questionnaire included information on parental characteristics (maternal and paternal age, maternal smoking status, hypertension or pre-eclampsia during pregnancy, exposure to diethylstilboestrol) and women’ birth characteristics (birth weight, length at birth, preterm birth, birth order and having been breast-fed). Analyses were conducted using unconditional logistic regression adjusting for age and recognized risk factors for breast cancer. Results: With the exception of maternal smoking (OR=0.57 [0.38-0.85]), there was no association between breast cancer risk and the other parental characteristics. We observed a J-shaped association between birth weight and breast cancer risk, with an OR of 1.54 [1.15-2.06] in women whose birth weight was 3500 grams or more as compared with women whose birth weight was 2500 to 3499 grams. We also observed an increased risk of breast cancer with an increase of birth order (OR=1.12 [0.91-1.37] for birth order 2 to 4; OR=1.42 [1.02-1.99] for birth order [[Unsupported Character - [[Unsupported Character - &amp;#61619;]]]] 5, p trend=0.04). No association were observed for women who have been breast-fed, for length at birth or preterm birth. Conclusion: Our results support the hypothesized association between intrauterine estrogens exposure and risk of breast cancer in daughters. 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 657. doi:1538-7445.AM2012-657
Granulocytopenia Occurring During the Administration of Lincomycin
Authors: Earl B. Brown
Journal: JAMA (1965)

DURING the evaluation of the clinical effectiveness of the use of lincomycin, granulocytopenia developed coincidentally in an adult patient. Of the thousands of persons in whom the drug was used during this nationwide investigation, three newborns were reported to have similar findings (personal communication from J. B. Lawson, Upjohn Pharmaceutical Co., Aug 10, 1964). Since the Food and Drug Administration has used this event as its basis for requiring the manufacturer to state that lincomycin might cause granulocytopenia, we thought it incumbent upon ourselves to report this case. <h3>Report of a Case</h3> A 37-year-old Negro woman was hospitalized at Misericordia Hospital on Dec 17, 1963 because of chills, fever, dyspnea, and a cough of three days' duration, productive of moderate quantities of purulent sputum. She stated that she had been in her usual state of health until seven days before admission when she noted the onset of cough and general
Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis
Authors: N.-C. Li, A. Lee, R. A Whitmer, M. Kivipelto, E. Lawler, L. E Kazis, B. Wolozin
Journal: BMJ (2010)

<h3>Introduction</h3> Corticosteroids are a mainstay in the treatment of moderately severe relapses of ulcerative colitis (UC), yet almost 50% of patients do not respond fully, with the risk of prolonged steroid use and side-effects. There is insufficient evidence to inform optimum treatment choice for steroid resistant disease. The aim of this study was to provide details of current practice in the management of steroid resistant UC. <h3>Methods</h3> A cross-sectional survey of Inflammatory Bowel Disease (IBD) healthcare professionals (HCPs) in the UK was conducted online using the Qualtrics platform. HCPs were invited to participate in the survey through professional networks: British Society of Gastroenterology IBD section, Royal College of Nursing IBD Nurses Network, and social media. Clinical scenarios representing patients with moderately severe UC with continuing symptoms (steroid resistant (SR)) and with relapse after steroid dose reduction (steroid dependent (SD)) were included – both thiopurine treated (TP+) and naïve (TP-). Data were analysed descriptively with chi-squared tests on outcomes of interest using R software. <h3>Results</h3> 387 HCPs visited the survey; 47% (168 HCPs) consented (68% medical; 30% nurses; median 7.5 years since appointment) across all UK regions. Definitions of steroid resistance varied: 68% indicating an incomplete response to prednisolone 40 mg/day after 2 weeks and after 4 weeks in a further 58%. Only 13% felt that SR and SD disease should be treated identically. Anti-TNF drugs would be most frequently offered in each scenario (SR: TP+ 95%; TP- 87%; SD: TP+ 88%; TP- 74%) with infliximab most frequently suggested; apart from SD TP- patients flaring at prednisolone 5 mg/day. Admission for IV steroids was offered more often for SR disease (32%) than for SD (12%). In SD scenarios, thiopurine treatment would be instigated in TP- patients flaring at 25 mg prednisolone or 5 mg/day in 49% and in 70% respectively. Anti-TNF treatment would be offered more frequently if patients are TP+ in both SR (TP+ 81%; TP- 62% p=0.004) or SD patients and particularly for those relapsing at 5 mg/day (Relapse at 25 mg/day: TP+ 78% TP- 49%, p&lt;0.001; Relapse at 5 mg/day TP+85% TP- 46%, p&lt;0.001). For both SR and SD disease, 43% and 58% respectively felt that endoscopy is not warranted. <h3>Conclusions</h3> There are important variations in practice in the UK in how to define, treat and use endoscopy in steroid resistant UC. Such variations need to be understood as part of initiatives to change practice - particularly to avoid excess steroid use - and in trial design.
Measurement of Glucose Concentration in the Presence of Coreactants with a Platinum Electrode
Authors: Harry Lerner, J Stuart Soeldner, Clark K Colton, Jose Giner
Journal: Diabetes Care (1982)

An implantable glucose sensor is being developed that is based on the use of a high-area platinum electrode. The sensor is operated in a controlled potential mode, in which the potential of the platinum working electrode versus an unpolarized reference electrode is periodically varied according to a preselected voltage-time regimen. The change in potential is accompanied by a flow of current between the platinum working electrode and a counter-electrode. This current serves to periodically rejuvenate the electrode surface and to provide a signal that is proportional to the glucose concentration. A method for analyzing this signal has been developed, the compensated net charge (CNC) method, that involves integration of the current over one complete potential cycle. This method significantly improves both the sensitivity and selectivity for determining glucose in the presence of the normal physiologic coreactants. For a solution containing glucose, amino acids, and urea, a change in glucose concentration from 50 to 150 mg/dl gives about a 50% change in the net charge. A change in the urea concentration from 20 to 40 mg/dl has no effect on the net charge. A change in the amino acids concentration from 35 to 65 mg/dl has little effect on the net charge above a glucose concentration of about 100 mg/dl. Negligible effects on the net charge have also been found for creatinine (0–1.5 mg/dl) and uric acid (0–4 mg/dl).
A Hypocaloric High-Protein Diet as Primary Therapy for Adults with Obesity-related Diabetes: Effective Long-Term Use in a Community Hospital
Authors: James D Fitz, Eileen M Sperling, Henry G Fein
Journal: Diabetes Care (1983)

The use of reducing diets as the sole therapy for the long-term management of obese diabetic patients has been generally unsuccessful. Most previous attempts took place with a few patients in university hospital clinical research centers. We placed 36 such patients on a hypocaloric high-protein food diet, consisting of 1.7–2.0 g protein/kg ideal body wt, during admission to a community hospital. After beginning this diet, patients could be weaned from sliding-scale regular insulin in an average of 1.9 days. Patients remained on this diet after discharge (mean hospital stay = 4.3 days), and complex carbohydrates were gradually added up to 80 g daily. Outpatient long-term management consisted of alternating biweekly visits to a sole nurse practitioner or physician or to a group discussion meeting. Follow-up averaged 41 wk, during which eight patients (22%) had sustained weight loss throughout and remained euglycemic. Twenty patients (56%) initially lost weight (average: 23% of ideal body weight), then plateaued weight, but have also remained euglycemic. Only eight patients, (22%) required insulin. Side effects of the diet were not serious in any patient; no one had myocardial irritability or serum potassium &amp;lt; 2.9 meq/L. This hypocaloric high-protein diet thus appears to be a generally successful means of weaning obese diabetic adult patients from insulin. This can be done rapidly, safely, and permanently in the community. Such diet therapy appears to require minimal laboratory and hospital resources that are available to all health care providers.
Not one academy but two
Authors: R. Smith
Journal: BMJ (1998)

Everybody in Britain should be grateful if the Academy of Medical Sciences that was launched this week can preserve and promote academic medicine—for it approaches a parlous state. But we don't need yet another body of old men with chains around their necks that dines, processes, and professes and offers a further source of advice to government that it can take or leave to suit its own ends. The academy must target its efforts and aim to be effective not grand.

A Martian—or even an American—might be surprised that after 50 years of unresolved debate about the need for an academy of medicine Britain suddenly has not one but two. The cognoscenti will understand well the difference between the Academy of Medical Royal Colleges and the Academy of Medical Sciences, but few ordinary doctors and almost no members of the public will. Medical students …
Tolerability of 3.5 versus 2.5 High&amp;ndash;Energy Transurethral Microwave Thermotherapy
Authors: E.A.E. Francisca, B.B.M. Kortmann, D.L. Floratos, L.A.L.M. Kiemeney, F.M.J. Debruyne, J.J.M.C.H. de la Rosette
Journal: European Urology (2000)
Liquid crystal thermography and C reactive protein in the detection of deep venous thrombosis.
Authors: E. A. Thomas, M. J. Cobby, E. Rhys Davies, W. D. Jeans, J. T. Whicher
Journal: BMJ (1989)

the anterolateral aspect of the right thigh of 3% body surface area.The skin was erythematous and oedematous but not blistering and was treated conservatively.The wound healed within three weeks, and he was discharged with no further treatment.
Lasting damage from the trastuzumab storm
Authors: Angela Raffle
Journal: BMJ (2006)

I n May 2005 the annual conference of the American Society for Clinical Oncology included a powerful speech by a US patients' advocate that highlighted the damage from “access advocacy,” whereby drug companies undermine research, licensing, and appraisal ( PLoS Medicine 2005;2: e358). Also presented were fast tracked abstracts of preliminary results for trials of trastuzumab (Herceptin) for localised breast cancer. Publicity for the society's annual conference is stage managed by its drug company sponsors, and the trastuzumab story buzzed through news wires worldwide.

Unlicensed, expensive new drugs without peer reviewed published data do not jump the queue over other priorities. If patients want drugs for cancer that are unlicensed or not approved by the National Institute for Health and Clinical Excellence (NICE), and hence not funded by the local primary care trust, they generally pay for them themselves. This, though regrettable, does not normally attract media comment. When trastuzumab hit the …
Alteration in left ventricular filling dynamics in early stage of diabetes mellitus of Otsuka long-evans Tokushima fatty (OLETF) rats
Authors: L. Yao, K. Mizushige, Y. Yu, T. Noma, A. Tomohiro, H. Kiyomoto, S. Nozaki, H. Matsuo
Journal: Journal of the American College of Cardiology (1998)
Baby P's GP is suspended for 12 months for "limited insight" into his failings
Authors: C. Dyer
Journal: BMJ (2010)

The GP who failed to take urgent action to protect the battered toddler Peter Connolly has been suspended from practising for 12 months but is allowed to stay on the medical register.

A General Medical Council fitness to practise panel held that Jerome Ikwueke’s failures were not wilful and that there was no risk that he would repeat them in the future. He had an “unblemished record,” testimonials described him as a “conscientious, hardworking, and caring doctor often going beyond the call of duty,” and he had undertaken child protection courses and had revised his practices at his …
Endoscopic Treatment for Laterally Spreading Tumors in the Colon
Authors: Y. Saito, T. Fujii, H. Kondo, H. Mukai, T. Yokota, T. Kozu, D. Saito
Journal: Endoscopy (2001)

Background and Study Aims: Laterally spreading tumors (LST) of the colon are best removed by endoscopic mucosal resection (EMR) as they extend laterally rather than vertically. Since they sometimes invade deeply into the submucosal layer, it is important to assess the depth of invasion endoscopically before treatment. In the present study, we examined the endoscopic features of a large number of LSTs in order to assess which features correlated with depth of invasion.
Aspergillus flavus endaortitis following aortic valvotomy
Authors: A. D. Malcolm, A. Bakerspigel, A. A. Enriquez
Journal: Thorax (1971)

Aspergillar endaortitis does not seem to have been described before in the English literature. Our patient had undergone aortic valvotomy and subsequently developed leg pains, migratory arthralgias, periarticular swelling, and general malaise. Mild intermittent pyrexia, evanescent petechiae, splinter haemorrhages, and peripheral small artery occlusion characterized the early course in hospital. Dramatic popliteal artery occlusion led to surgical recovery of embolic material packed with mycelia of <i>Aspergillus flavus</i>, but the patient died despite intravenous amphotericin B therapy. Necropsy revealed endaortitis and aspergilli were demonstrated in the wall of a saccular dilatation of the ascending aorta close to non-absorbable sutures. The relevant literature is reviewed and attention is drawn to the current implications of knowledge relating to risk factors, diagnosis, and treatment. We suggest that cardiovascular aspergillosis will now be encountered more frequently and that a different therapeutic approach is justified.
Iron and the liver: Update 2008
Authors: Yves Deugnier, Pierre Brissot, Olivier Loréal
Journal: Journal of Hepatology (2008)

The cross-talk which has taken place in recent years between clinicians and scientists has resulted in a greater understanding of iron metabolism with the discovery of new iron-related genes including the hepcidin gene which plays a critical role in regulating systemic iron homeostasis. Consequently, the distinction between (a) genetic iron-overload disorders including haemochromatosis related to mutations in the HFE, hemojuvelin, transferrin receptor 2 and hepcidin genes and (b) non-haemochromatotic conditions related to mutations in the ferroportin, ceruloplasmin, transferrin and di-metal transporter 1 genes, and (c) acquired iron-overload syndromes has become easier. However, major challenges still remain which include our understanding of the regulation of hepcidin production, the identification of environmental and genetic modifiers of iron burden and organ damage in iron-overload syndromes, especially HFE haemochromatosis, indications regarding the new oral chelator, deferasirox, and the development of new therapeutic tools interacting with the regulation of iron metabolism. The cross-talk which has taken place in recent years between clinicians and scientists has resulted in a greater understanding of iron metabolism with the discovery of new iron-related genes including the hepcidin gene which plays a critical role in regulating systemic iron homeostasis. Consequently, the distinction between (a) genetic iron-overload disorders including haemochromatosis related to mutations in the HFE, hemojuvelin, transferrin receptor 2 and hepcidin genes and (b) non-haemochromatotic conditions related to mutations in the ferroportin, ceruloplasmin, transferrin and di-metal transporter 1 genes, and (c) acquired iron-overload syndromes has become easier. However, major challenges still remain which include our understanding of the regulation of hepcidin production, the identification of environmental and genetic modifiers of iron burden and organ damage in iron-overload syndromes, especially HFE haemochromatosis, indications regarding the new oral chelator, deferasirox, and the development of new therapeutic tools interacting with the regulation of iron metabolism.
Normalization of bundle branch block patterns by distal His bundle pacing. Clinical and experimental evidence of longitudinal dissociation in the pathologic his bundle.
Authors: N El-Sherif, F Amay-Y-Leon, C Schonfield, B J Scherlag, K Rosen, R Lazzara, C Wyndham
Journal: Circulation (1978)

Clinical and experimental observations in which bundle branch block patterns (BBBP) in ECG leads were normalized by distal His bundle (H) pacing are reported. The clinical material includes four patients with acute right BBBP secondary to anterior wall myocardial infarction and three patients with chronic left BBBP. Six of the seven patients had a prolonged H-V interval (60-85 msec) including three who showed evidence of an intra-H conduction delay (IHCD) with split H (H and H'). Distal H pacing from a right-sided electrode catheter normalized the BBBP with a stimulus-to-QRS (PI-V) interval 20-35 msec shorter than the H-V interval and almost identical to the H'-V interval in the three patients with documented IHCD. In 18 dogs ligation of the anterior septal artery resulted in IHCF with split H associated with right or left BBBP. Distal H pacing from catheter and/or plunge wire electrodes normalized the BBBP in 12 experiments (67%) with a PI-V interval identical to the H'-V interval. H pacing was selective and direct stimulation of myocardium was excluded by monitoring the high ventricular septal electrogram. The clinical and experimental observations are discussed as evidence that functional longitudinal dissociation is probably only operative in the pathologic H due to selectively greater depression of conduction in the transverse interconnections.
76 IL28 β/IFN-λ3 RS12979860 POLYMORPHISM IN PATIENTS WITH END STAGE LIVER DISEASE: RELATIONSHIP WITH THE OCCURRENCE OF HCC
Authors: S. Bignulin, E. Falleti, E. Fontanini, A. Cussigh, S. Cmet, E. Fornasiere, E. Fumolo, D. Bitetto, C. Fabris, R. Minisini, M. Pirisi, P. Toniutto
Journal: Journal of Hepatology (2010)
Donor type microchimerism is an infrequent event following liver transplantation and is not associated with graft acceptance
Authors: S Norris
Journal: Hepatology (1997)

Donor-type microchimerism, the presence of a minority population of donor-derived haematopoietic cells following solid organ transplantation, has been postulated as a mechanism for induction of donor-specific graft tolerance. The stability, frequency, and relevance of microchimerism with respect to long-term outcome, however, remains uncertain. Using a polymerase chain reaction (PCR)-based method of microsatellite analysis of highly polymorphic short tandem repeat sequences (STRs) to detect donor-type cells, DNA from 11 patients was analyzed prospectively at specific time points for 12 months following liver transplantation, and from a further six patients retrospectively 2 years after liver transplantation. Using a panel of STRs, transient peripheral blood donor microchimerism was detected in 2 of 11 patients at a single time-point following transplantation, but persistent evidence of donor-derived cells was not observed during the study period. Analysis of DNA extracted from skin and duodenum in two patients likewise failed to show donor-type cells at these sites. None of the six patients in the retrospective arm showed donor microchimerism, resulting in an overall detection rate of 1.58%. These results suggest that donor microchimerism following liver transplantation is an infrequent event, and that the generation of graft tolerance is independent of microchimerism.