tbuckley/cabot-search huggingface dataset:
The Association between Common Vitamin D Receptor Gene Variations and Osteoporosis: A Participant-Level Meta-Analysis
Authors: André G. Uitterlinden, Stuart H. Ralston, Maria Luisa Brandi, Alisoun H. Carey, Daniel Grinberg, Bente L. Langdahl, Paul Lips, Roman Lorenc, Barbara Obermayer-Pietsch, Jonathan Reeve, David M. Reid, Antonietta Amedei, Amelia Bassiti, Mariona Bustamante, Lise Bjerre Husted, Adolfo Diez-Perez, Harald Dobnig, Alison M. Dunning, Anna Enjuanes, Astrid Fahrleitner-Pammer, Yue Fang, Elzbieta Karczmarewicz, Marcin Kruk, Johannes P.T.M. van Leeuwen, Carmelo Mavilia, Joyce B.J. van Meurs, Jon Mangion, Fiona E.A. McGuigan, Huibert A.P. Pols, Wilfried Renner, Fernando Rivadeneira, Natasja M. van Schoor, Serena Scollen, Rachael E. Sherlock, John P.A. Ioannidis
Journal: Annals of Internal Medicine (2006)

Background: Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in the genetic regulation of bone mineral density (BMD). However, the clinical impact of these variants remains unclear. Objective: To evaluate the relation between VDR polymorphisms, BMD, and fractures. Design: Prospective multicenter large-scale association study. Setting: The Genetic Markers for Osteoporosis consortium, involving 9 European research teams. Participants: 26 242 participants (18 405 women). Measurements: Cdx2 promoter, FokI, BsmI, ApaI, and TaqI polymorphisms; BMD at the femoral neck and the lumbar spine by dual x-ray absorptiometry; and fractures. Results: Comparisons of BMD at the lumbar spine and femoral neck showed nonsignificant differences less than 0.011 g/cm2 for any genotype with or without adjustments. A total of 6067 participants reported a history of fracture, and 2088 had vertebral fractures. For all VDR alleles, odds ratios for fractures were very close to 1.00 (range, 0.98 to 1.02) and collectively the 95% CIs ranged from 0.94 (lowest) to 1.07 (highest). For vertebral fractures, we observed a 9% (95% CI, 0% to 18%; P = 0.039) risk reduction for the Cdx2 A-allele (13% risk reduction in a dominant model). Limitations: The authors analyzed only selected VDR polymorphisms. Heterogeneity was detected in some analyses and may reflect some differences in collection of fracture data across cohorts. Not all fractures were related to osteoporosis. Conclusions: The FokI, BsmI, ApaI, and TaqI VDR polymorphisms are not associated with BMD or with fractures, but the Cdx2 polymorphism may be associated with risk for vertebral fractures. *For a list of study investigators, see the Appendix.
FOUR DIFFERENT TYPES OF BLOOD SUGAR CURVE IN ONE PATIENT WITHIN SEVENTEEN MONTHS
Authors: F. J. G. Lishman
Journal: BMJ (1930)

TIIE followiing details appear to be of soimle pathiological inlterest, anid miay also.be of imlportance ini colnllexioln with life insuranice of glycosuric subjects.An obese butcher, aged 50, came under treatment in January, 1229, for ostea-artliritis cf the knieeanid ankle-joints; owing to tlhc discovery of glycosuria on routine examination, a blood sugar exariniatioin was made (A), The cuirve was found to be nornmal, but indicated a low renal threslhold of 0.128 per cent.sugar.
A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential
Authors: Gesine Kögler, Sandra Sensken, Judith A. Airey, Thorsten Trapp, Markus Müschen, Niklas Feldhahn, Stefanie Liedtke, Rüdiger V. Sorg, Johannes Fischer, Claudia Rosenbaum, Susanne Greschat, Andreas Knipper, Jörg Bender, Özer Degistirici, Jizong Gao, Arnold I. Caplan, Evan J. Colletti, Graça Almeida-Porada, Hans W. Müller, Esmail Zanjani, Peter Wernet
Journal: The Journal of Experimental Medicine (2004)

Here a new, intrinsically pluripotent, CD45-negative population from human cord blood, termed unrestricted somatic stem cells (USSCs) is described. This rare population grows adherently and can be expanded to 1015 cells without losing pluripotency. In vitro USSCs showed homogeneous differentiation into osteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes and neurons that express neurofilament, sodium channel protein, and various neurotransmitter phenotypes. Stereotactic implantation of USSCs into intact adult rat brain revealed that human Tau-positive cells persisted for up to 3 mo and showed migratory activity and a typical neuron-like morphology. In vivo differentiation of USSCs along mesodermal and endodermal pathways was demonstrated in animal models. Bony reconstitution was observed after transplantation of USSC-loaded calcium phosphate cylinders in nude rat femurs. Chondrogenesis occurred after transplanting cell-loaded gelfoam sponges into nude mice. Transplantation of USSCs in a noninjury model, the preimmune fetal sheep, resulted in up to 5% human hematopoietic engraftment. More than 20% albumin-producing human parenchymal hepatic cells with absence of cell fusion and substantial numbers of human cardiomyocytes in both atria and ventricles of the sheep heart were detected many months after USSC transplantation. No tumor formation was observed in any of these animals.
Erythema dyschromicum perstans in an HIV antibody-positive man
Authors: M.R. Nelson, A.G. Lawrence, R.C.D. Staughton, B.G. Gazzard
Journal: British Journal of Dermatology (1992)

Journal Article Erythema dyschromicum perstans in an HIV antibody‐positive man Get access M.R. Nelson, M.R. Nelson AIDS Unit, Westminster Hospital, London SWIP 2AP, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.G. Lawrence, A.G. Lawrence AIDS Unit, Westminster Hospital, London SWIP 2AP, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.C.D. Staughton, R.C.D. Staughton AIDS Unit, Westminster Hospital, London SWIP 2AP, U.K. Search for other works by this author on: Oxford Academic Google Scholar B.G. Gazzard B.G. Gazzard AIDS Unit, Westminster Hospital, London SWIP 2AP, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 6, 1 December 1992, Page 658, https://doi.org/10.1111/j.1365-2133.1992.tb14886.x Published: 01 December 1992
Ectopic bone formation using an injectable biphasic calcium phosphate/Si-HPMC hydrogel composite loaded with undifferentiated bone marrow stromal cells
Authors: C TROJANI, F BOUKHECHBA, J SCIMECA, F VANDENBOS, J MICHIELS, G DACULSI, P BOILEAU, P WEISS, G CARLE, N ROCHET
Journal: Biomaterials (2006)
The Bradshaw Lecture ON THE PLEURAE: PLEURAL EFFUSION AND ITS TREATMENT: Delivered before the Royal College of Physicians of London, November 5th, 1907
Authors: J. Barr
Journal: BMJ (1907)

PRESIDENT AND GEENTLEMEN,-We have met to-day to do honour to the memory of a distinguished mem- ber of this College, a memory which has been thus perpetuated by the foundation of this lectureship.Until redently Dr
A New Method for Assessing the Effect of Replication on DNA Base Composition Asymmetry
Authors: A. Necsulea, J. R. Lobry
Journal: Molecular Biology and Evolution (2007)

DNA base composition asymmetry is at the basis of numerous in silico methods for the detection of the origin and terminus of replication in prokaryotes. However, most of these methods are unable to identify the evolutionary mechanisms that cause the base composition asymmetry. In prokaryotic chromosomes, due to the tendency for coorientation between replication and transcription, compositional biases that discriminate the leading strand from the lagging strand can be produced by 2 superposing mechanisms: replication-associated mutation bias and coding sequence–associated bias (such as transcription-related mutational processes or selective pressures on codon usage). We propose here a new method for the analysis of nucleotide composition asymmetry that allows the decoupling of replication-related and coding sequence–related mechanisms. This method is inspired by a recent work (Nikolaou and Almirantis 2005) that proposed an artificial chromosomal rearrangement meant to create a perfect gene orientation bias. We show that the study of nucleotide skews on the artificially rearranged chromosomes is a powerful means to assess the contributions of the 2 types of mechanisms in generating the base composition asymmetry. We applied our method to all completely sequenced prokaryotic chromosomes available. Our results confirm that in most species the replication mechanism has an important effect on base composition asymmetry but also that it has different impacts on GC and AT skews. We also analyzed the variability in AT skew direction encountered in prokaryotes. In disagreement with a recent report (Worning et al. 2006), we find that the polymerase-α subunits encoded in a genome are not sufficient to predict the sign of the AT skew on its leading strand for replication.
Microsatellite Instability Markers for Identifying Early-Onset Colorectal Cancers Caused by Germ-Line Mutations in DNA Mismatch Repair Genes
Authors: Leeanne J. Mead, Mark A. Jenkins, Joanne Young, Simon G. Royce, Letitia Smith, D. James B. St. John, Finlay Macrae, Graham G. Giles, John L. Hopper, Melissa C. Southey
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Microsatellite instability (MSI) testing of colorectal cancer tumors is used as a screening tool to identify patients most likely to be mismatch repair (MMR) gene mutation carriers. We wanted to examine which microsatellite markers currently used to detect MSI best predict early-onset colorectal cancer caused by germ-line mutations in MMR genes. Experimental Design: Invasive primary tumors from a population-based sample of 107 cases of colorectal cancer diagnosed before age 45 years and tested for germ-line mutations in MLH1, MSH2, MSH6, and PMS2 and MMR protein expression were screened for MSI using the National Cancer Institute panel and an expanded 10-microsatellite marker panel. Results: The National Cancer Institute five-marker panel system scored 31 (29%) as NCIMSI-High, 13 (12%) as NCIMSI-Low, and 63 (59%) as NCIMS-Stable. The 10-marker panel classified 18 (17%) as 10MSI-High, 17 (16%) as 10MSI-Low, and 72 (67%) as 10MS-Stable. Of the 26 cancers that lacked the expression of at least one MMR gene, 24 (92%) were positive for some level of MSI (using either microsatellite panel). The mononucleotide repeats Bat26, Bat40, and Myb were unstable in all 10MSI-High cancers and all MLH1 and MSH2 mutation carriers (100% sensitive). Bat40 and Bat25 were unstable in all tumors of MSH6 mutation carriers (100% sensitive). Bat40 was unstable in all MMR gene mutation carriers (100% sensitive). By incorporating seven mononucleotide repeats markers into the 10-marker panel, we were able to distinguish the carriers of MSH6 mutations (all scored 10MSI-Low) from the MLH1 and MSH2 mutation carriers (all scored 10MSI-High). Conclusions: In early-onset colorectal cancer, a microsatellite panel containing a high proportion of mononuclear repeats can distinguish between tumors caused by MLH1 and MSH2 mutations from those caused by MSH6 mutations.
Sustained effect after lowering high-dose infliximab in patients with rheumatoid arthritis: a prospective dose titration study
Authors: B J F van den Bemt, A A den Broeder, G F Snijders, Y A Hekster, P L C M van Riel, B Benraad, G J Wolbink, F H J van den Hoogen
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> In clinical trials only a small subset of patients with rheumatoid arthritis (RA) benefits from higher than standard dose of infliximab (&gt;3 mg/kg/8 weeks). However, dose escalation of infliximab is frequently applied in clinical practice. Individual adjustment of infliximab treatment based on actual disease activity, instead of subjective clinical judgement, could prevent possible unwarranted dose escalation. <h3>Methods:</h3> The infliximab dose of all patients with RA treated at our centre was decreased from 5 mg/kg to 3 mg/kg, leaving dosing intervals unaltered. Subsequently patients were followed for at least three infusions. At every visit, 28-joint Disease Activity Score (DAS28), infliximab serum trough levels and anti-infliximab antibody levels were assessed. Inversed European League Against Rheumatism (EULAR) criteria (flare criteria) were used as the endpoint. <h3>Results:</h3> A total of 18 patients were included in the study. Mean (SD) DAS28 scores before dose reduction and after first and second low dose were 3.2 (1.2), 3.2 (1.8) and 3.3 (1.2), respectively (values not significant). One patient (6%, 95% CI 0% to 17%) developed a persistent flare that subsided after increasing infliximab doses and one patient stopped infliximab because of a lupus-like reaction. In all other patients (n = 16) lowering infliximab resulted in unaltered disease activity. Infliximab levels showed that most patients had either low- (&lt;1 mg/litre) or high (&gt;5 mg/litre) serum trough levels. Anti-infliximab antibodies were detected in four patients. <h3>Conclusion:</h3> Infliximab dosages of 5 mg/kg can be lowered in the majority of patients with RA using DAS28-guided dose titration without increase of disease activity. Lowering the dose of infliximab should be considered in every patient receiving higher doses infliximab.
Intratumoral <i>De Novo</i> Steroid Synthesis Activates Androgen Receptor in Castration-Resistant Prostate Cancer and Is Upregulated by Treatment with CYP17A1 Inhibitors
Authors: Changmeng Cai, Sen Chen, Patrick Ng, Glenn J. Bubley, Peter S. Nelson, Elahe A. Mostaghel, Brett Marck, Alvin M. Matsumoto, Nicholas I. Simon, Hongyun Wang, Shaoyong Chen, Steven P. Balk
Journal: Cancer Research (2011)

Relapse of castration-resistant prostate cancer (CRPC) that occurs after androgen deprivation therapy of primary prostate cancer can be mediated by reactivation of the androgen receptor (AR). One important mechanism mediating this AR reactivation is intratumoral conversion of the weak adrenal androgens DHEA and androstenedione into the AR ligands testosterone and dihydrotestosterone. DHEA and androstenedione are synthesized by the adrenals through the sequential actions of the cytochrome P450 enzymes CYP11A1 and CYP17A1, so that CYP17A1 inhibitors such as abiraterone are effective therapies for CRPC. However, the significance of intratumoral CYP17A1 and de novo androgen synthesis from cholesterol in CRPC, and the mechanisms contributing to CYP17A1 inhibitor resistance/relapse, remain to be determined. We report that AR activity in castration-resistant VCaP tumor xenografts can be restored through CYP17A1-dependent de novo androgen synthesis, and that abiraterone treatment of these xenografts imposes selective pressure for increased intratumoral expression of CYP17A1, thereby generating a mechanism for development of resistance to CYP17A1 inhibitors. Supporting the clinical relevance of this mechanism, we found that intratumoral expression of CYP17A1 was markedly increased in tumor biopsies from CRPC patients after CYP17A1 inhibitor therapy. We further show that CRPC cells expressing a progesterone responsive T877A mutant AR are not CYP17A1 dependent, but that AR activity in these cells is still steroid dependent and mediated by upstream CYP11A1-dependent intraturmoral pregnenolone/progesterone synthesis. Together, our results indicate that CRPCs resistant to CYP17A1 inhibition may remain steroid dependent and therefore responsive to therapies that can further suppress de novo intratumoral steroid synthesis.
Morphological characteristics of monosodium urate: a transmission electron microscopic study of intact natural and synthetic crystals.
Authors: H Paul, A J Reginato, H R Schumacher
Journal: Annals of the Rheumatic Diseases (1983)

Transmission electron microscopic studies of synthetic and natural monosodium urate crystals dried on formvar coated grids showed identical internal structures in all crystals. At higher magnification the crystals9 surface showed angular or wavy irregularities, and more rarely some crystals appeared to have other tiny crystals on the surface. Protein-like surface coating was not observed except in crystals from one asymptomatic patient in whom synovial fluid was loaded with monosodium urate crystals, but no inflammatory cells were present. Heated synthetic monosodium urate crystals retained the ultrastructural characteristics in their interior but they lost their needle or rod-like shape. Transmission electron microscopic study of monosodium urate crystals dried on formvar coated grids provides a quick method of investigating crystal ultrastructure.
Molecular mechanisms of blister formation in bullous impetigo and staphylococcal scalded skin syndrome
Authors: Yasushi Hanakawa, Norman M. Schechter, Chenyan Lin, Luis Garza, Hong Li, Takayuki Yamaguchi, Yasuyuki Fudaba, Koji Nishifuji, Motoyuki Sugai, Masayuki Amagai, John R. Stanley
Journal: Journal of Clinical Investigation (2002)

Bullous impetigo due to Staphylococcus aureus is one of the most common bacterial infections of man, and its generalized form, staphylococcal scalded skin syndrome (SSSS), is a frequent manifestation of staphylococcal epidemics in neonatal nurseries. Both diseases are mediated by exfoliative toxins (ETs), which show exquisite pathologic specificity in blistering only the superficial epidermis. We show that these toxins act as serine proteases with extremely focused molecular specificity to cleave mouse and human desmoglein 1 (Dsg1) once after glutamic acid residue 381 between extracellular domains 3 and 4. Mutation of the predicted catalytically active serine to alanine completely inhibits cleavage. The mutated ETs bind specifically to Dsg1 by immunofluorescence colocalization and by coimmunoprecipitation. Thus, ETs, through specific recognition and proteolytic cleavage of one structurally critical peptide bond in an adhesion molecule, cause its dysfunction and allow S. aureus to spread under the stratum corneum, the main barrier of the skin, explaining how, although they circulate through the entire body in SSSS, they cause pathology only in the superficial epidermis.
Cellular Action of Calcium Channel Blocking Drugs
Authors: A Schwartz, D J Triggle
Journal: Annual Review of Medicine (1984)

The calcium antagonists are an exciting "class" of drugs that are already making an important impact in the treatment of coronary artery disease. All three drugs in use in the US, verapamil, nifedipine, and diltiazem, are effective coronary vasodilators. In addition, verapamil and diltiazem have antiarrhythmic activity against certain supraventricular abnormalities. Since the calcium antagonists dilate peripheral resistance vessels, they may also be useful in hypertension. There are reports also that they may be effective in migraine headache, probably because of their "antispastic" activity in cerebral vessels. Since calcium is ultimately involved in all processes that require stimulation, either electrical or chemical, it is not surprising that drugs whose primary effect appears to be an inhibition of the entry of calcium across or through cell membranes should exhibit a wide spectrum of therapeutic activity. The stereospecific binding of dihydropyridine derivatives to membrane preparations, and the effects of those and other calcium antagonists on the binding process, should yield important information on the mechanisms of calcium antagonist action.
Rigor tension in single skinned rat cardiac cell: role of myofibrillar creatine kinase
Authors: Vladimir I Veksler, Patrick Lechene, Khalid Matrougui, Renée Ventura-Clapier
Journal: Cardiovascular Research (1997)

Objective: To elucidate the role of bound creatine kinase in adenine nucleotide compartmentation in myofibrils, the effects of this enzyme's substrates and products on rigor tension were studied in using isolated skinned rat cardiomyocytes rather than fibres, to avoid restrictions due to concentration gradients within the multicellular preparations. Methods: A new experimental set-up was built to allow continuous and stable measurements of force developed by cells. Triton X-100-treated cardiomyocytes were glued between a glass holder and the needle of a galvanometer. A feedback system allowed the precise measurement of force by recording the coil current necessary to prevent movement of the needle. Results: At very low [Ca2+] (pCa 7), as MgATP level decreased, rigor tension appeared. In the absence of phosphocreatine (PCr), this tension started to rise at MgATP concentrations several times higher than in the presence of 12 mM PCr. In the absence of PCr, the pMgATP/tension curves of single cells usually had a complicated relationship which could not be analyzed by a simple Hill equation. In the absence of PCr, 250 μM MgADP strongly potentiated rigor tension development in the 1 mM–3 μM range of [MgATP]; at 100 μM MgATP, in the presence of MgADP, the tension was 4.6 times higher than in the absence of MgADP. Addition of 12 mM PCr immediately eliminated rigor. Finally, in the presence of 100 μM MgATP and 250 μM MgADP, a decrease in PCr resulted in rigor; the half-maximal contracture being recorded at 1 mM PCr. Conclusions: These results indicate a myofibrillar compartmentation of adenine nucleotides influenced by bound creatine kinase, since at equal MgATP concentrations in extramyofibrillar milieu the response of myofibrils strongly depends on the presence of PCr. Local accumulation of ADP in myofibrils due to a fall in cellular PCr and inability of myofibrillar creatine kinase to rephosphorylate ADP produced by myosin ATPase could be an important mechanism of diastolic tension rise in ischaemic conditions.
P85 Pictorial representation of respiratory examination in hospital notes
Authors: N. Mahmood, C. Gobbett, S. Malik, C. Houghton, G. N. G. M. Kwong
Journal: Thorax (2010)

Good record keeping maximises patient safety and quality of care. The Royal College of Physicians recommends that ‘medical records should have a standardised structure and layout’ (<i>RCP Generic Record Keeping Standards</i> 2007). Pictorial representation of respiratory examination using a cartoon of the lungs annotated with lines, squiggles, crosses and musical notes is commonplace despite lack of standardisation and formal teaching. Our study aimed to assess the accuracy of interpretation and the rationale behind use of pictorial representation. <h3>Methods</h3> Questionnaire survey correlating six common pictorial representations A–F (see Abstract P85 Figure 1) with clinical findings as follows: 1=coarse crepitations, 2=wheeze, 3=bronchial breath sounds, 4=decreased bronchial sounds, 5=pneumonectomy, 6=pleural effusion, 7=rhonchi, 8=fine end inspiratory crepitations, 9=bibasal crepitations, 10=transmitted upper airway sounds, 11=absent breath sounds, 12=pneumothorax, 13=other(specify). Multiple responses were allowed for the same picture. <h3>Results</h3> 88 clinicians completed the survey (Foundation Year n=44, Specialist Trainee n=10, Specialist Registrar n=13, Consultant n=16, other n=3). 74/88 (84%) admitted to routinely drawing pictures. Of these 71/74(96%) also recorded findings in written text. 23/71 (32%) could not provide a reason for their use of drawings though 26/71(37%) reported that it aided communication. Most learned their behaviour from senior colleagues (22/76), own observation (16/76) or medical school (27/76). The closest associations were for Pictures C (77/78 responses, 99%=normal) and E (94/102,92%=wheeze/rhonchi combined). Crosses were commonly interpreted as crepitations in Pictures B (89/101,88%=fine and bibasal combined) and F (66/94, 70%=coarse). Pleural effusion was most commonly linked to Pictures A (35/107, 33%) and D (75/98, 77%) though both of these had an additional eight and four interpretations respectively. <h3>Conclusion</h3> The majority of doctors use pictorial representation to record respiratory examination. Lack of standardisation leads to variation in annotation and potentially alternative interpretation by others. With the exception of Picture C, the use of pictures alone is unreliable. Reassuringly for patient safety, most doctors also write down their findings. Pictorial representation is most often informally learned and appears to be well established in UK medical practice.