tbuckley/cabot-search huggingface dataset:
Opposite Evolutionary Effects between Different Alternative Splicing Patterns
Authors: F.-C. Chen, S.-M. Chaw, Y.-H. Tzeng, S.-S. Wang, T.-J. Chuang
Journal: Molecular Biology and Evolution (2007)

Alternative splicing (AS) has been recognized as a mechanism of relaxing selection pressure on protein subsequences. Here, we show that AS may also yield contrary evolutionary effects. We compare the evolutionary rates of 2 types of alternatively spliced exons (ASEs)-simple and complex. The former does not change the boundaries of its flanking exons, whereas the latter does. By analyzing over 26,000 human-mouse orthologous exons, we demonstrate that complex ASEs have lower Ka and Ka/Ks ratio and higher Ks than constitutively spliced exons (CSEs), whereas simple ASEs have evolutionary rates to the opposite of CSEs. Our results indicate that complex ASEs are subject to stronger selection pressure than CSEs at the protein level, but the trend is reversed at the RNA level. Therefore, the previous view that ASEs accelerate evolution of protein subsequences needs to be modified.
Results of Nephrectomy in Hypertension Associated with Unilateral Renal Disease
Authors: R. G. Luke, A. C. Kennedy, J. D. Briggs, N. W. Struthers, W. B. Stirling
Journal: BMJ (1968)

Nephrectomy has been carried out in 34 patients with hypertension associated with unilateral parenchymal renal disease (28 with unilateral pyelonephritis, 3 tuberculosis, 2 hypoplasia, and 1 adenocarcinoma). In 13 of the patients the blood pressure was corrected, in four it was improved, and in 17 it was unaffected. The intravenous pyelogram (by the infusion technique with nephrotomography if necessary) and renogram give adequate information in most patients with unilateral parenchymal renal disease but may need to be supplemented by aortography, or retrograde pyelography, or divided renal function studies in a few special circumstances. When the function of the damaged kidney is less than 25% of the total (which is well maintained), and the contralateral kidney is intact, nephrectomy is recommended provided the hypertension is significant; success is more likely in younger patients with a short history of hypertension.
Hard end points are needed for intensive glycaemic control in patients with type 2 diabetes
Authors: J. S. Yudkin, K. J. Lipska
Journal: BMJ (2012)

Hemmingsen and colleagues’ meta-analysis of intensive glucose lowering showed a reduction of 12% (95% confidence interval 3% to 21%) in microvascular events comprising composite end points of varying importance.1 Photocoagulation made a large contribution, but ophthalmologists are aware of glycaemic control when deciding on interventions. In the UK Prospective Diabetes Study (UKPDS) photocoagulation and cataract extraction contributed importantly to the end point, seemingly …
`Erythropoietic' protoporphyria and cirrhosis in sisters
Authors: R. P. H. Thompson, E. A. Molland, D. C. Nicholson, C. H. Gray
Journal: Gut (1973)

The clinical and histopathological features of two sisters with erythropoietic protoporphyria and liver disease are described. They had unusually severe photosensitivity with blistering, and both died at the age of 31 from cirrhosis. The association of erythropoietic protoporphyria with several hepatic abnormalities is discussed.
Unmasking of a novel target for blocking harmful Na+ coupled acid extrusion: electrogenic Na+–HCO3− symport
Authors: Jos M.J Lamers
Journal: Cardiovascular Research (2001)

See article by Kandoudi et al. \[22\] (pages 388–396 in this issue). 

Many cellular functions of myocardium, such as the sensitivity of the myofilaments to Ca2+, the activity of the rate-limiting enzyme of the glycolysis (1-phosphofructokinase) and number of functional gap junctions between adjacent myocytes, are strongly affected by lowering of pHi [1]. In fact, acidosis depresses contractility in cardiac myocytes by affecting virtually every step in the excitation–contraction coupling [2]. On the other hand, there is also evidence that cytoplasmic alkalinization is an intracellular messenger mediating growth responses of various stimuli such as stretch, neurohumoral factors and growth factors [3]. Therefore, in order to preserve proper cardiac functioning, pHi of the myocytes is maintained within narrow limits. Normally myocardial pHi is about one pH unit more alkaline than would be expected if H+ was in electrochemical equilibrium [4–7]. This indicates the existence of mechanisms actively removing acid equivalents from the cytoplasm in addition to the intracellular pHi-dependent buffering capacities (protein histidyl residues, inorganic phosphate and CO2–HCO3−) which maintain constant pHi in the cardiomyocyte [4–6,8]. In general, cells regulate their pHi on top of intracellular buffering capacity, by balancing the opposing actions of acid extruding and loading mechanisms [9]. Acid extruders are transporters that either export H+ from the cytoplasm or import a base (e.g., HCO3−) into the cytoplasm or they merely are passively diffusing molecules such as CO2. The only known transport proteins that function as acid loaders are HCO3− transporters (e.g., the electrogenic Cl−–HCO3− antiporter). It is obvious that the metabolic processes that (in)directly generate cytoplasmic H+ are the major acid loaders [9]. Historically, the … 

* Tel.: +31-10-408-7335; fax: +31-10-408-9472 lamers{at}bc1.fgg.eur.nl
Disseminated Herpes Zoster Complicating Chronic Lymphatic Leukemia
Authors: Gerald P. Rodnan, Geoffrey W. Rake
Journal: New England Journal of Medicine (1956)

THE occurrence of generalized herpes zoster in the course of leukemia was first noted by Fischl in 1914.1 The association is apparently not uncommon, for Wile and Holman1 were able to compile 34 such cases. In all but a few cases the leukemia was of the chronic lymphatic type.This report deals with such an occurrence of herpes zoster and disseminated varicelliform eruption in a man and chronic lymphatic leukemia and presents the findings of electron-microscope examination of the fluid from disseminated vesicles.Case ReportM.S., a 57-year-old hospital porter, was admitted to the Maimonides Hospital on June 23, 1950, . . .
Encapsulation of rotavirus into poly(lactide-co-glycolide) microspheres
Authors: Cecilia Sturesson, Per Artursson, Raouf Ghaderi, Kari Johansen, Ali Mirazimi, Ingrid Uhnoo, Lennart Svensson, None Ann-Christine Albertsson, Johan Carlfors
Journal: Journal of Controlled Release (1999)
A METHOD FOR THE RAPID DIAGNOSIS OF DIPHTHERIA BY THE GENERAL PRACTITIONER.
Authors: FRANK M. WOOD
Journal: JAMA (1907)

The necessity for the early diagnosis of diphtheria is often painfully apparent to the general practitioner, as failure in that regard too often results in involvement of the larynx, especially in children, while this, in turn, frequently ends in the early, demise of the child. I, therefore, offer this method to the profession, with the hope that it may facilitate the diagnosis of this disease: It is necessary first to obtain agriculture from the throat or nose of the patient by means of a swab of absorbent cotton or the platinum needle. A swab which is very convenient for this purpose may be made as follows: An ordinary test-tube is sterilized in the Bunsen or alcohol flame. A wire is bent with a loop at both ends, and made just long enough to fit the tube. One end of this wire is then wound with wick asbestos in the form
Australia-SH Antigen in Hepatitis Patients in London
Authors: Y. Cossart, P. E. Taylor, J. Vahrman, A. J. Zuckerman
Journal: BMJ (1969)

Australia-SH antigen was found in 11 out of 27 sera (40%) obtained from patients with acute viral hepatitis soon after their admission to hospital. Six out of 11 positive sera were collected within the first 12 days of illness; die remaining five were collected between the 13th and 30th days. The antigen was detected by immunodiffusion in agarose gel, five different indicator sera containing Australia-SH antibodies being used. The specificity of these sera was found to be very similar.All of the patients' sera were examined independently by two separate laboratories. The results obtained by the laboratories were in close agreement, though the techniques varied in detail.
Bone formation induced by strontium modified calcium phosphate cement in critical-size metaphyseal fracture defects in ovariectomized rats
Authors: Ulrich Thormann, Seemun Ray, Ursula Sommer, Thaqif ElKhassawna, Tanja Rehling, Marvin Hundgeburth, Anja Henß, Marcus Rohnke, Jürgen Janek, Katrin S. Lips, Christian Heiss, Gudrun Schlewitz, Gabor Szalay, Matthias Schumacher, Michael Gelinsky, Reinhard Schnettler, Volker Alt
Journal: Biomaterials (2013)

The first objective was to investigate new bone formation in a critical-size metaphyseal defect in the femur of ovariectomized rats filled with a strontium modified calcium phosphate cement (SrCPC) compared to calcium phosphate cement (CPC) and empty defects. Second, detection of strontium release from the materials as well as calcium and collagen mass distribution in the fracture defect should be targeted by time of flight secondary ion mass spectrometry (TOF-SIMS). 45 female Sprague-Dawley rats were randomly assigned to three different treatment groups: (1) SrCPC (n = 15), (2) CPC (n = 15), and (3) empty defect (n = 15). Bilateral ovariectomy was performed and three months after multi-deficient diet, the left femur of all animals underwent a 4 mm wedge-shaped metaphyseal osteotomy that was internally fixed with a T-shaped plate. The defect was then either filled with SrCPC or CPC or was left empty. After 6 weeks, histomorphometric analysis showed a statistically significant increase in bone formation of SrCPC compared to CPC (p = 0.005) and the empty defect (p = 0.002) in the former fracture defect zone. Furthermore, there was a statistically significant higher bone formation at the tissue-implant interface in the SrCPC group compared to the CPC group (p < 0.0001). These data were confirmed by immunohistochemistry revealing an increase in bone-morphogenic protein 2, osteocalcin and osteoprotegerin expression and a statistically significant higher gene expression of alkaline phosphatase, collagen10a1 and osteocalcin in the SrCPC group compared to CPC. TOF-SIMS analysis showed a high release of Sr from the SrCPC into the interface region in this area compared to CPC suggesting that improved bone formation is attributable to the released Sr from the SrCPC.
Comparison of Train-of-Four and Best Clinical Assessment during Continuous Paralysis
Authors: CHARLIE STRANGE, LEIGH VAUGHAN, CHERYL FRANKLIN, JIM JOHNSON
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Train-of-four (TOF) monitoring is recommended in published guidelines during use of continuous-infusion neuromuscular blocking agents (NMB) in the intensive care unit (ICU). To test that recommendation, dual protocols were established in a medical ICU after intensive nursing education. Paralyzed patients received either TOF monitoring with a goal of three twitches or best clinical assessment while receiving atracurium by continuous infusion. Demographics and mean duration of paralysis of 20 patients in the TOF group were no different than that of the 16 patients in the best clinical assessment group. Although most patients demonstrated atracurium tolerance over time, there was no difference between groups in total mg (+/- SEM) infused (10,460 +/- 2,409 versus 9,201 +/- 3,237) or mean microgram/kg/min (15.2 +/- 1.5 versus 12.0 +/- 1.1). The time to clinical recovery was no different between groups (50 +/- 10 versus 45 +/- 12 min). Two complications occurred in the TOF group, with pulmonary emboli despite prophylaxis and an unrecognized cerebrovascular accident in one patient each. We conclude that careful titration of NMB using clinical bedside markers should remain the standard of care with these drugs.
Ciro de Quadros
Authors: S. Arie
Journal: BMJ (2014)

<h3>Abstract</h3> Lethality after respiratory infection with influenza A virus (IAV) is associated with potent immune activation and lung tissue damage. In a well-controlled animal model of infection, we sought to determine if one could predict lethality using transcriptional information obtained from whole blood early after influenza virus exposure. We started with publicly available transcriptomic data from the lung, which is the primary site of the infection and pathology, to derive a multigene transcriptional signature of death reflective of innate inflammation associated with tissue damage. We refined this affected tissue signature with data from infected mouse and human blood to develop and validate a machine learning model that can robustly predict survival in mice after IAV challenge using data obtained from as little as 10 μl of blood from early time points post infection. Furthermore, in genetically identical, cohoused mice infected with the same viral bolus, the same model can predict the lethality of individual animals but, intriguingly, only within a specific time window that overlapped with the early effector phase of adaptive immunity. These findings raise the possibility of predicting disease outcome in respiratory virus infections with blood transcriptional data and pave the way for translating such approaches to humans.
DR4 prevalence related to the age at disease onset in female patients with rheumatoid arthritis.
Authors: J.M Hazes, B.A Dijkmans, J.M Hoevers, J.J Janson, R.R de Vries, J.P Vandenbroucke, A Cats
Journal: Annals of the Rheumatic Diseases (1989)

The prevalence of HLA-DR4 in relation to age at disease onset was calculated in 226 consecutive female patients with definite or classical rheumatoid arthritis (RA). A slight increase in the prevalence of DR4 with age at RA onset was found. This appeared to be due to the low percentage of rheumatoid factor (RF) positivity in the youngest age groups; the DR4 prevalence in the RF positive patients was constant for all decades--that is, approximately 60%. A previously reported declining trend of DR4 prevalence in women with RA in relation to age of RA onset may be due to the disease heterogeneity of the patients included in that study.
Reduced E-Cadherin Expression Is Associated with Increased Lymph Node Metastasis and Unfavorable Prognosis in Non-small Cell Lung Cancer
Authors: MAARTEN A. SULZER, MATHIE P. G. LEERS, JAN A. van NOORD, EWALD C. M. BOLLEN, PAUL H. M. H. THEUNISSEN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

E-cadherin is a calcium-dependent, epithelial cell adhesion molecule whose reduced expression has been associated with tumor dedifferentiation and increased lymph node metastasis in clinical studies involving several carcinomas. In this study, 111 patients who had previously undergone complete resection and systematic mediastinal lymph node dissection for non-small cell lung cancer (NSCLC) were studied retrospectively. In the primary tumor, as well as in the lymph node metastases, E-cadherin expression was detected by immunohistochemistry using a monoclonal antibody (HECD-1; Takara, Otsu, Japan). There was a significant inverse correlation between E-cadherin expression and lymph node stage (Pearson correlation coefficient − 0.52, p = 0.0001) as well as tumor differentiation (Pearson correlation coefficient − 0.27, p = 0.005). Moreover, Kaplan and Meier survival estimates showed a significant correlation between E-cadherin expression and patient survival in log rank testing (p = 0.006). In the patient group with the highest proportion of E-cadherin positive tumor cells, 60% of the patients were still estimated to be alive at 36 mo, versus 32% of the patients in the group classified as showing negative E-cadherin expression. Our findings provide clinical evidence that reduced E-cadherin expression is associated with tumor dedifferentiation, increased lymphogenous metastasis and poor survival. It seems therefore that E-cadherin expression might be an important prognostic factor in NSCLC.
Abstract 2868: EGCG inhibits pancreatic cancer growth in xenografts and KrasG12D transgenic mice models
Authors: Luke Marsh, Sharmila Shankar, Rakesh K. Srivastava
Journal: Cancer Research (2010)

Abstract FoxO (forkhead box O) transcription factors are crucial regulators of cell fate. This function of FoxO proteins relies on their ability to control diverse functions such as proliferation, differentiation, DNA repair and apoptosis. Constitutively active AKT and ERK in cancer cells have been shown to phosphorylate FoxO transcription factors (FKHR, FKHRL1 and AFX), which bind to protein 14-3-3 and sequester in the cytoplasm. In the absence of survival signals, FoxO proteins dephosphorylate, translocate to the nucleus and upregulate a series of target genes, thereby promoting cell cycle arrest and apoptosis. EGCG, a component of green tea, exerts antiproliferative and proapoptotic actions on a number of different cancer cell lines through diverse mechanisms. However, the mechanisms by which EGCG inhibits cell proliferation and induces apoptosis are poorly understood. EGCG inhibited viability and induced apoptosis in human pancreatic cancer cell lines. EGCG induces PTEN expression and inhibits Akt phosphorylation in pancreatic cancer Hs766T, AsPC-1, MIA PaCa-2 and PANC-1 cells. Treatment of PANC-1 cells with EGCG caused a decrease in ERK phosphorylation, and an increase in JNK phosphorylation. Overexpression of FOXO1, FOXO3a, and FOXO4 inhibited cell viability in PANC-1 cells. The inhibitory effects of EGCG on cell viability were further enhanced when cells were transfected with FOXO1, FOXO3a, and FOXO4. EGCG enhances FOXO-DNA binding activity. EGCG-induced FOXO transcriptional activity was further enhanced in the presence of FOXO1-TM, FOXO3a-TM, and FOXO4-TM. Interestingly, EGCG inhibited pancreatic cancer growth in xenograft, orthotopic and KrasG12D transgenic mice models. In conclusion, our data demonstrate that EGCG can inhibit pancreatic cancer growth through multiple mechanisms and thus can be used for the pancreatic cancer prevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2868.
Directors of Calcutta hospital are arrested after fire kills 90
Authors: Z. Kmietowicz
Journal: BMJ (2011)

Six directors of the Amri Hospital in Calcutta have been arrested and charged with culpable homicide after at least 90 people are thought to have died in a fire that broke out at the facility on 9 December. They have been denied bail.

Reports suggest that the 190 bed private hospital had been warned about inadequate …
The Physician and the Quality of Life
Authors: George L. Spaeth
Journal: JAMA (1974)

<h3>To the Editor.—</h3> There is one sentence that appears to need challenging in Dimond's otherwise excellent article (228:1117, 1974). He states, "Whether he seeks the task or not, the physician will, in these next 30 years, be forced into a larger role of science and moral counselor to society." Present events seem to contradict this statement, for there is distressingly little evidence that physicians, as a group, are indeed concerning themselves with the fundamental moral and scientific problems that face society. And, on the other hand, there is increasing evidence that other segments of our population, most specifically the legislators, have become justifiably tired of trying to involve physicians in a constructive way, and are increasingly ignoring and even purposely bypassing the physician's point of view. It is not these other segments that are primarily responsible for such action, but rather the persisting resistance of physicians to meet the challenges
TCT-323 Higher Adverse Clinical Event Rates in Young African American Women Undergoing Percutaneous Coronary Intervention: Results from the NHLBI Dynamic Registry
Authors: Kelly C. Epps, Elizabeth M. Holper, Helen Vlachos, Faith Selzer, Hansie Mathelier, Peter Groeneveld, Robert Wilensky
Journal: Journal of the American College of Cardiology (2013)
Evaluation and Management of HIV-Infected Women
Authors: Alexandra M. Levine
Journal: Annals of Internal Medicine (2002)

The rate of newly diagnosed AIDS in the United States is increasing fastest in women, who are infected with HIV primarily through heterosexual transmission. Approximately 60% of these women are African American, and 18% are Latina. A gynecologic infection is the most common symptom that leads to initial medical evaluation. Specific studies at baseline should include CD4 lymphocyte count, HIV-1 RNA level, and gynecologic examination with Papanicolaou smear. Decisions about initiation of antiretroviral therapy depend on the patient's clinical diagnoses, her willingness to adhere to treatment, and CD4 lymphocyte and HIV-1 RNA levels. Levels of HIV-1 RNA may be somewhat lower in women than in men at the same CD4 count, whereas women have higher CD4 lymphocyte counts at the time of AIDS diagnosis. However, prospective trials have not yet indicated the need to change the threshold CD4 lymphocyte counts or HIV-RNA levels for initiation of therapy in women. The efficacy of antiretroviral therapy appears to be similar in men and women, although women are more likely to experience toxicities. Abnormal Papanicolaou smears occur in approximately 40% of women at baseline, and 58% are infected with human papillomavirus. The prevalence of both conditions increases with lower CD4 lymphocyte counts and higher HIV-1 RNA levels. Precursor lesions to cervical cancer may be effectively treated, but almost 50% recur within 1 year, mandating careful follow-up. Referral should be sought for specialized gynecologic care and for issues related to HIV itself, since survival is prolonged in patients treated by physicians who are experienced in treating HIV. When they are provided the same access to care, HIV-infected women have similar prognoses as HIV-infected men.
Carcinogenicity of some drugs and herbal products
Authors: Yann Grosse, Dana Loomis, Béatrice Lauby-Secretan, Fatiha El Ghissassi, Véronique Bouvard, Lamia Benbrahim-Tallaa, Neela Guha, Robert Baan, Heidi Mattock, Kurt Straif
Journal: The Lancet Oncology (2013)
Recent Advances in Genetics, Diagnosis, Localization, and Treatment of Pheochromocytoma
Authors: Karel Pacak, W. Marston Linehan, Graeme Eisenhofer, McClellan M. Walther, David S. Goldstein
Journal: Annals of Internal Medicine (2001)

Pheochromocytoma is a rare but important tumor of chromaffin cells that is frequently considered in the evaluation of hypertension, arrhythmias, or panic disorder and in the follow-up of patients with particular genetic diseases. This report provides an update about the genetics, neurochemical diagnosis, localization by imaging, and surgical management of pheochromocytoma. Specific mutations of the RETproto-oncogene cause familial predisposition to pheochromocytoma in multiple endocrine neoplasia type II, and mutations in the von Hippel–Lindau tumor suppressor gene cause familial disposition to pheochromocytoma in von Hippel–Lindau disease. Recent findings demonstrating extraordinarily high sensitivity of plasma levels of metanephrines for detecting pheochromocytoma have led to an algorithm for clinical diagnostic steps. Nuclear imaging approaches, such as 123I-metaiodobenzylguanidine scintigraphy and 6-[18F]fluorodopamine positron emission tomography, enhance both diagnosis and localization of the tumor, as described in an algorithm for patients with positive biochemical test results. Since pheochromocytoma is often benign, surgical resection by laparoscopic adrenalectomy can be curative. Areas requiring further work include determining appropriate follow-up of patients with familial pheochromocytoma, elucidating the bases for phenotypic differences, improving both specificity and sensitivity of biochemical tests, optimizing cost-effectiveness of diagnostic imaging, and testing the risk for tumor recurrence after partial adrenalectomy.