tbuckley/cabot-search huggingface dataset:
STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS
Authors: Oswald T. Avery, James M. Neill
Journal: The Journal of Experimental Medicine (1924)

In the present paper methods have been described for the preparation of sterile extracts of pneumococci. These extracts may be obtained by dissolving the bacteria in broth cultures by means of bile, or by extraction of the cellular substances by repeated freezing and thawing of broth or saline suspensions of unwashed cells. Under special precautions these extracts may be passed through Berkefeld filters without loss of potency. In this procedure, as in all other manipulations incident to their preparation, the extracts should be protected as far as possible from contact with air. All extracts were proved sterile by cultural and animal tests. Sterile extracts of unwashed pneumococcus cells promptly form peroxide on exposure to air. Peroxide formation is almost as active in extracts aerated at 2 degrees C. as in those exposed to the air at room temperature. Detectable amounts of peroxide may be produced by these cell extracts within the reaction range of pH 5 to 9, the optimal zone lying at reactions less acid than pH 6. The peroxide-forming activity of the extracts is gradually diminished by prolonged exposure to 55 degrees C., and is completely destroyed by heating at 65 degrees C. for 5 minutes. Cell extracts of pneumococci which have been thoroughly washed prior to extraction in salt or phosphate solutions exhibit no peroxide-forming activity. These extracts of washed cells may be activated by the addition of the cell washings, yeast extract, or muscle infusion.
HORMONAL REGULATION OF HUMAN MUSCLE PROTEIN METABOLISM
Authors: Olav E. Rooyackers, K. Sreekumaran Nair
Journal: Annual Review of Nutrition (1997)

▪ Abstract A continuous turnover of protein (synthesis and breakdown) maintains the functional integrity and quality of skeletal muscle. Hormones are important regulators of this remodeling process. Anabolic hormones stimulate human muscle growth mainly by increasing protein synthesis (growth hormone, insulin-like growth factors, and testosterone) or by decreasing protein breakdown (insulin). Unlike in growing animals, insulin's main anabolic effect on muscle protein in adult humans is an inhibition of protein breakdown. Protein synthesis is stimulated only in the presence of a high amino acid supply. A combination of the stress hormones (glucagon, glucocorticoids, and catecholamines) cause muscle catabolism, but the effects of the individual hormones on human muscle and their mechanisms of action remain to be clearly defined. Although thyroid hormone is essential during growth, both an excess and a deficiency cause muscle wasting by yet unknown mechanisms. A greater understanding of the regulation of human muscle protein metabolism is essential to elucidate mechanisms of muscle wasting.
Distribution of distal femoral osteophytes in a human skeletal population
Authors: L. Shepstone
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVES</h3> To examine objectively spatial patterns of osteophytes around the distal end of the femur and to identify distinct subgroups. <h3>METHODS</h3> A sample of 107 human femora from a large skeletal population were selected for study. These femora included subjects with evidence of late stage osteoarthritis (that is, with eburnation present) and those with no such evidence. The location of osteophytes was recorded using a video camera and digitised computer images were extracted. Multidimensional scaling was used to identify clusters of femora based upon osteophyte location. <h3>RESULTS</h3> A distinct subgroup of femora was identified with osteophytes present only within the intercondylar notch region. None of these subjects had any evidence of eburnation. <h3>CONCLUSIONS</h3> This finding adds to an earlier study based on radiographs. Osteophytes located within the intercondylar notch of the femur appear to be a distinct subset, which may occur either as an early stage of knee osteoarthritis or for some independent reason.
Analysis of hMLH1 Missense Mutations in East Asian Patients with Suspected Hereditary Nonpolyposis Colorectal Cancer
Authors: Yimei Fan, Wei Wang, Ming Zhu, Jiji Zhou, Jingyuan Peng, Lizhi Xu, Zichun Hua, Xiang Gao, Yaping Wang
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Germ line mutations in the DNA mismatch repair gene hMLH1 are a frequent cause of hereditary nonpolyposis colorectal cancer and about one-third of these are missense mutations. Several missense mutations in hMLH1 have frequently been detected in East Asian patients with suspected hereditary nonpolyposis colorectal cancer, but their pathogenic role has not been extensively assessed. The aim of this study was to perform functional analyses of these variants and their association with gastrointestinal cancer in East Asians. Experimental Design: Altogether, 10 hMLH1 variants were analyzed by yeast two-hybrid and coimmunoprecipitation assays. Results: The carboxyl-terminal replacements Q542L, L549P, L574P, and P581L in hMLH1 resulted in complete loss of activity in both yeast two-hybrid and coimmunoprecipitation tests and thus might be considered as pathogenic. The amino-terminal variants S46I, G65D, G67R, and R217C did not affect complex formation with hPMS2 in coimmunoprecipitation, but partly or fully lost their activity in yeast two-hybrid assay, and we suggested that these variants might reduce the efficiency of the heterodimer to go into the nucleus and thus the mismatch repair function might be blocked or reduced. The V384D and the Q701K variant resulted in the interaction of hMLH1 with hPMS2 at reduced efficiency and might raise the gastrointestinal cancer risk of the mutation carriers. Conclusions: This work availably evaluated the functional consequences of some missense mutations not previously determined in the hMLH1 gene and might be useful for the clinical diagnosis of hereditary gastrointestinal cancer, especially in East Asians.
Tumor-Associated Alterations in Caspase-14 Expression in Epithelial Malignancies
Authors: Maryla Krajewska, Hoguen Kim, Eunah Shin, Susan Kennedy, Michael J. Duffy, Yick F. Wong, David Marr, Jowita Mikolajczyk, Ahmed Shabaik, Ivo Meinhold-Heerlein, Xianshu Huang, Steven Banares, Hirad Hedayat, John C. Reed, Stan Krajewski
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Caspase-14 is unique among caspase family proteases in that its proteolytic processing has been principally associated with epithelial cell differentiation rather than apoptosis or inflammation. We investigated caspase-14 expression in several types of human epithelial malignancy by immunohistochemistry, correlating results with stage, histologic grade, and patient survival. Experimental Design: Tumor-associated alterations in caspase-14 expression were observed for cervical, ovarian, breast, gastric, and colon cancers. Results: In cervical (n = 445), ovarian (n = 91), and colon (n = 106) specimens, expression of caspase-14 was significantly reduced in cancers compared with normal epithelium. Decreases in caspase-14 immunopositivity correlated with the histologic progression of cervical cancer (P &amp;lt; 0.0001, ANOVA). In localized gastric cancers, caspase-14 immunostaining was significantly lower in poorly differentiated tumors compared with well-differentiated tumors (P = 0.02, Pearson's χ2 analysis). Lower caspase-14 expression was associated with advanced clinical stage in ovarian cancer (P = 0.04, ANOVA) and with shorter overall survival among ovarian cancer patients with serous tumors (n = 62) in both univariate (P = 0.005) and multivariate (P = 0.03) analysis. Lower caspase-14 expression correlated with shorter overall survival among patients with T3N0M0 stage gastric cancers (n = 94; P = 0.006, log-rank test). In contrast to cervical, ovarian, and colon cancers, caspase-14 expression was increased in ductal carcinoma in situ and invasive cancers compared with normal mammary epithelium (P = 0.001, t test). Conclusions: The findings reveal tumor-specific alterations in caspase-14 expression and suggest that differences in its expression may define subsets of epithelial cancers with distinct clinical behaviors.
Livedo Reticularis in Patients With Parkinsonism Receiving Amantadine
Authors: C. Norman Shealy
Journal: JAMA (1970)

Asymptomatic livedo reticularis has appeared in ten of 18 female patients with parkinsonism treated with amantadine hydrochloride. Although no serious effects have been seen to date, a livedo reticularis type manifestation has been associated at times with serious collagen disorders such as periarteritis nodosa and lupus erythematosus. Although amantadine has distinct beneficial effects in parkinsonism, long-term use should be viewed with some caution.
Two more people in UK die from swine flu, as swabbing policy ends in "hot spot" areas
Authors: A. O'Dowd
Journal: BMJ (2009)

Two more people have died in the United Kingdom after contracting the A/H1N1 virus, while some GPs in so called hot spot areas are now handling the virus in a different way from how they did at the start of the epidemic.

A young schoolgirl in Birmingham and a 73 year old man in Paisley have died. Officials said they had tested positive for the virus, but it has not yet been confirmed whether the virus was the main cause of their death.

The man, who has not yet been named, died at the Royal Alexandra Hospital, the same hospital where the first flu victim, 38 year old Jacqueline Fleming, died in June.

The girl, 6 year old Sameerah Ahmad, died at the Birmingham Children’s Hospital. In both cases the patients had serious underlying health problems.

As the BMJ went to press on Tuesday 30 June the confirmed number of cases worldwide …
Frank Netter, MD: 'command performance' in medical art
Authors: Helene Cole
Journal: JAMA (1986)

Virtually every medical student has at some time wished for the ability to preserve on paper that which he or she sees in the laboratory or clinic. Whether it is a stage in the dissection of a cadaver, a pathology specimen, a histologic section, or an unusual finding during a physical examination, the desire to capture an observation, before it fades, is compelling. One young medical student in the late 1920s was uniquely capable of synthesizing the medical knowledge he was accumulating and then of rendering these complex facts in an astonishingly clear pictorial representation. To the satisfaction of thousands of subsequent students and physicians, he has continued to practice his art of medicine to this very day. The artist is Frank H. Netter, MD, whose 80th birthday anniversary coincides with the date (April 25) of this issue ofThe Journal. Netter still is busy illustrating the<i>CIBA Collection of</i>
Directional Difference of Conduction Velocity in the Cardiac Ventricular Syncytium Studied by Microelectrodes
Authors: TOYOMI SANO, NORIYUKI TAKAYAMA, TAKIO SHIMAMOTO
Journal: Circulation Research (1959)

In the theory of electrocardiography the direction of myocardial fibers has been almost ignored. In order to evaluate whether this is proper or not, directional difference of conduction velocity in the ventricular syncytium was examined by capillary microelectrodes. Conduction velocity in the direction of myocardial fibers was found to be usually several times larger than that vertical to them. This difference is significantly large and cannot be ignored even though rapidity of conduction through Purkinje fibers is considered. This statement became more applicable in various abnormal conditions. Thus it is concluded that the direction of myocardial fibers should be given more attention in discussion of propagation of excitation waves in the cardiac ventricle.
Is tidal expiratory flow limitation predictive of sleep-related disorders in the elderly?
Authors: M. Guillot, F. Costes, E. Sforza, D. Maudoux, L. Bertoletti, J. C. Barthelemy, F. Roche
Journal: European Respiratory Journal (2010)

Sleep-related disorders represent an important health burden and their prevalence increases with age. In patients with snoring or sleepiness, the presence of expiratory flow limitation (EFL), determined via the negative expiratory pressure (NEP) method, is related to the apnoea/hypopnoea index (AHI). In this study, we examined whether EFL can be used to predict obstructive sleep apnoea syndrome (OSAS) in healthy asymptomatic older subjects. A group of 72-yr-old subjects (n = 448, 44% males) with a mean body mass index of 25.5±3.8 kg·m(-2) were examined. All subjects underwent spirometry, NEP (-5 cmH(2)O, sitting position) and ventilatory polygraphy (VP). Spirometry was within normal values in 88% of the group and EFL was present in 143 (32%) subjects with a higher prevalence in females (89 out of 249 versus 54 out of 199 in females and males, respectively). VP showed an AHI<15 h(-1) in 238 subjects (53%) and OSAS with an AHI ≥15 h(-1) in 47%. EFL was found in 15% of subjects with OSAS. Consequently, EFL had low sensitivity and specificity in the prediction of OSAS (31.4% and 67.7%, respectively). We conclude that the prevalence of EFL is elevated in healthy older subjects and cannot be used to predict the presence of sleep-related disorders in an older population.
Treatment of the cutaneous pain of acute herpes zoster with 9% lidocaine (base) in petrolatum/paraffin ointment
Authors: James Riopelle, Arturo Lopez-Anaya, Randall C. Cork, Donna Heitler, Jane Eyrich, Armayne Dunston, Arthur J. Riopelle, William Johnson, Avery Ragan, M. Naraghi
Journal: Journal of the American Academy of Dermatology (1994)
Spirometry in primary care: is it good enough to face demands like World COPD Day?: Table 1
Authors: T. Schermer, T. Eaton, R. Pauwels, C. van Weel
Journal: European Respiratory Journal (2003)

On November 19th this year, World Chronic Obstructive Pulmonary Disease (COPD) Day 2003, people worldwide willbe encouraged to review their respiratory health status and consult a doctor in case of certain symptoms 1. Spirometry would be regarded as an integral component ofthis consultation. Additionally, asymptomatic smokers >40 yrs will be advised to have their lung function checked 1. Thus, a likely and desirable outcome of World COPD Day could be a considerable and perhaps dramatic increase indemand for spirometry. This is a potentially daunting prospect with important implications in terms of the availability and utilisation of healthcare resources. It is therefore not only timely but essential to reflect on the current status ofspirometry in primary care.

Thus far, a New Zealand study which was reported in 1999presents the only, but extremely welcome, randomised prospective evaluation of the implementation of spirometry in primary care practice formally assessing both the impact of training and quality assurance 2. The results of this study should be placed in the context of the growing prevalence of COPD which presents an increasing burden on healthcare resources globally 3. An essential requirement would seem to be the development of high quality spirometry by family physicians on a large scale. The implications are sobering. Family physicians already diagnose 5–10 new cases annually 4, a figure expected to increase in the coming decades. This figure, albeit dramatic, still underestimates the true challenge of COPD. The burden of the disease in the community is much higher and for a substantial number of patients COPD remains undiagnosed and consequently untreated 5. Cigarette smoking remains the leading cause of COPD and …
Interaction of the heart and its close and distant neighbours: report of the Meeting of the ESC Working Groups Myocardial Function and Cellular Biology
Authors: Emilio Hirsch, Denise Hilfiker-Kleiner, Jean-Luc Balligand, Guido Tarone, Leon De Windt, Johann Bauersachs, Peter Ferdinandy, Sean Davidson, Derek J. Hausenloy, Rainer Schulz
Journal: Cardiovascular Research (2013)

Intercellular and inter-organ communication is required to maintain homoeostasis in multicellular organisms. Given its life-supporting function, the heart is at the centre of a heavily studied network of interactions. Despite the long-recognized ability to receive and relay inputs to and from far and close neighbours, surprising new networks of interactions as well as new communication factors and mechanisms are currently emerging. The Myocardial Function and the Cellular Biology of the Heart Working groups of the European Society of Cardiology convened during 2–5 May 2013 to discuss emerging data and ongoing studies on intercellular and inter-organ communication, in health and disease.

Cells interact through either direct contact or secreted agonists. The signal transduction machinery inside cells eventually translates interactions with limited numbers of agonists into a cellular response. This process of scanty molecules being pinpointed by high-affinity receptors is now flanked by other emerging mechanisms of communication that involve highly abundant messengers binding to relatively low-affinity detectors. Two novel intercellular communication paths are currently arising: the flooding of cells with secreted vesicles, the so-called exosomes, with various but information-rich contents, and the sensing of different species of circulating RNA, such as miRNAs that, once captured, elicit post-transcriptional regulation of gene expression, and the extracellular RNAs (eRNA) that, from the outside of cells, trigger membrane enzyme activation and generation of classical receptor agonists.

### 2.1 Exosomes and miRNA

An exciting new concept in the field of intercellular and inter-organ communication is the idea that microscopic vesicles may ferry proteins and RNA through interstitial fluid and blood. Building on this concept, miRNA and proteins from plasma microvesicles and exosomes may offer a great potential as biomarkers for cardiovascular risk and cellular injury. Specific miRNAs act as master regulators of angiogenesis, cardiomyocyte proliferation, and regulation of cell survival. In particular, the importance of miR-199, which seems to regulate a …
Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial
Authors: M Hallek, K Fischer, G Fingerle-Rowson, AM Fink, R Busch, J Mayer, M Hensel, G Hopfinger, G Hess, U von Grünhagen, M Bergmann, J Catalano, PL Zinzani, F Caligaris-Cappio, JF Seymour, A Berrebi, U Jäger, B Cazin, M Trneny, A Westermann, CM Wendtner, BF Eichhorst, P Staib, A Bühler, D Winkler, T Zenz, S Böttcher, M Ritgen, M Mendila, M Kneba, H Döhner, S Stilgenbauer
Journal: The Lancet (2010)
Sensitizing the Slit Diaphragm with TRPC6 Ion Channels
Authors: Clemens C. Mo[Combining Diaeresis]ller, Jan Flesche, Jochen Reiser
Journal: Journal of the American Society of Nephrology (2008)

Physiologic permeability of the glomerular capillary depends on the normal structure of podocyte foot processes forming a functioning slit diaphragm in between. Mutations in several podocyte genes as well as specific molecular pathways have been identified as the cause for progressive kidney failure with urinary protein loss. Podocyte injury is a hallmark of glomerular disease, which is generally displayed by the rearrangement of the podocyte slit diaphragm and the actin cytoskeleton. Recent studies demonstrate a unique role for the Ca<sup>2+</sup>-permeable ion channel protein TRPC6 as a regulator of glomerular ultrafiltration. In both genetic and acquired forms of proteinuric kidney disease, dysregulation of podocyte TRPC6 plays a pathogenic role. This article illustrates how recent findings add to emerging concepts in podocyte biology, particularly mechanosensation and signaling at the slit diaphragm.
Low-dose interleukin-11 in patients with bone marrow failure: update of the M. D. Anderson Cancer Center experience
Authors: A.-M. Tsimberidou, F.J. Giles, I. Khouri, C. Bueso-Ramos, S. Pilat, D.A. Thomas, J. Cortes, R. Kurzrock
Journal: Annals of Oncology (2004)
MPs want to drop second doctor's signature for abortion
Authors: Adrian O'Dowd
Journal: BMJ (2007)

Only one doctor's permission should be necessary for a woman to have an abortion, rather than the current UK legal requirement for two, MPs have recommended.

The 24 week time limit for abortions to take place should be kept, the MPs also recommended in the newly published report from the parliamentary Science and Technology Committee on whether abortion laws need updating.

The report, which focuses on issues capable of scientific evaluation rather than ethical considerations, says that the MPs are concerned that the requirement for two signatures to allow an abortion could be causing delays in access to abortion services and found no evidence of its …
Epidemic Dynamics Revealed in Dengue Evolution
Authors: S.N. Bennett, A.J. Drummond, D.D. Kapan, M.A. Suchard, J.L. Munoz-Jordan, O.G. Pybus, E.C. Holmes, D.J. Gubler
Journal: Molecular Biology and Evolution (2009)

Dengue is an emerging tropical disease infecting tens of millions of people annually. A febrile illness with potentially severe hemorrhagic manifestations, dengue is caused by mosquito-borne viruses (DENV-1 to -4) that are maintained in endemic transmission in large urban centers of the tropics with periodic epidemic cycles at 3- to 5-year intervals. Puerto Rico (PR), a major population center in the Caribbean, has experienced increasingly severe epidemics since multiple dengue serotypes were introduced beginning in the late 1970s. We document the phylodynamics of DENV-4 between 1981 and 1998, a period of dramatic ecological expansion during which evolutionary change also occurs. The timescale of viral evolution is sufficiently short that viral transmission dynamics can be elucidated from genetic diversity data. Specifically, by combining virus sequence data with confirmed case counts in PR over these two decades, we show that the pattern of cyclic epidemics is strongly correlated with coalescent estimates of effective population size that have been estimated from sampled virus sequences using Bayesian Markov Chain Monte Carlo methods. Thus, we show that the observed epidemiologic dynamics are correlated with similar fluctuations in diversity, including severe interepidemic reductions in genetic diversity compatible with population bottlenecks that may greatly impact DENV evolutionary dynamics. Mean effective population sizes based on genetic data appear to increase prior to isolation counts, suggesting a potential bias in the latter and justifying more active surveillance of DENV activity. Our analysis explicitly integrates epidemiologic and sequence data in a joint model that could be used to further explore transmission models of infectious disease.