bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory T cell epitopes (Tregitopes) in IgG induce tolerance in vivo and lack immunogenicity per se
Authors: Su Yan , Rossi Robert , De Groot Anne S , Scott David W
Published: June 2013

Tregitopes are a set of epitopes, derived from IgG, that bind to MHCII, activate nTregs, and promote tolerance. We have now confirmed that coadministration of Tregitopes with a range of proteins (autoantigens and nominal antigens, such as OVA) in vitro and in vivo leads to suppression of T cell and antibody responses to the test antigens. In this study, we demonstrate that Tregitopes are not immunogenic in vivo even when emulsified with strong adjuvants, such as IFA or CFA. Moreover, in vivo administration of Tregitopes with IFA or CFA does not induce Th1 or Th2 cytokine expression under restimulation conditions in vitro. We investigated tolerance induction by codelivering Tregitopes with OVA using B cells. When B cells were pulsed with OVA plus Tregitopes and transferred into naïve mice, we found that cellular and humoral immune responses to the OVA were suppressed. As a result of their ability to induce Tregs and the absence of immunogenicity in the context of strong adjuvants, Tregitopes might be considered a novel immunomodulatory approach for the suppression of immune responses to protein therapeutics (such as FVIII and mAb), as well as for treatment of autoimmune diseases.
Membrane cholesterol modulates the hyaluronan-binding ability of CD44 in T lymphocytes and controls rolling under shear flow
Authors: Murai Toshiyuki , Sato Chikara , Sato Mari , Nishiyama Hidetoshi , Suga Mitsuo , Mio Kazuhiro , Kawashima Hiroto
Published: June 2013

The adhesion of circulating lymphocytes to the surface of vascular endothelial cells is important for their recruitment from blood to secondary lymphoid organs and to inflammatory sites. CD44 is a key adhesion molecule for this interaction, and its ligand-binding ability is tightly regulated. Here we show that the hyaluronan-binding ability of CD44 in T cells is upregulated by the depletion of membrane cholesterol with methyl-β-cyclodextrin (MβCD), which disintegrates lipid rafts, cholesterol- and sphingolipid-enriched membrane microdomains. Increasing concentrations of MβCD led to a dose-dependent decrease in cellular cholesterol content and to upregulation of the hyaluronan-binding. Additionally, a cholesterol-binding agent filipin also increased the hyaluronan-binding. Cholesterol depletion caused CD44 to be dispersed from cholesterol-enriched membrane microdomains. Cholesterol depletion also increased the number of cells undergoing rolling adhesion under physiological flow conditions. Our results suggest that CD44's ligand-binding ability is governed by its cholesterol-dependent allocation to membrane microdomains at the cell surface. These findings provide novel insight into the regulation of T-cell adhesion under blood flow.
Nonsense-mediated mRNA decay of collagen – emerging complexity in RNA surveillance mechanisms
Authors: Fang Yiwen , Bateman John F. , Mercer Julian F. , Lamandé Shireen R.
Published: June 2013

Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved mRNA surveillance system that degrades mRNA transcripts that harbour a premature translation-termination codon (PTC), thus reducing the synthesis of truncated proteins that would otherwise have deleterious effects. Although extensive research has identified a conserved repertoire of NMD factors, these studies have been performed with a restricted set of genes and gene constructs with relatively few exons. As a consequence, NMD mechanisms are poorly understood for genes with large 3′ terminal exons, and the applicability of the current models to large multi-exon genes is not clear. In this Commentary, we present an overview of the current understanding of NMD and discuss how analysis of nonsense mutations in the collagen gene family has provided new mechanistic insights into this process. Although NMD of the collagen genes with numerous small exons is consistent with the widely accepted exon-junction complex (EJC)-dependent model, the degradation of Col10a1 transcripts with nonsense mutations cannot be explained by any of the current NMD models. Col10a1 NMD might represent a fail-safe mechanism for genes that have large 3′ terminal exons. Defining the mechanistic complexity of NMD is important to allow us to understand the pathophysiology of the numerous genetic disorders caused by PTC mutations.
The Toxoplasma gondii centrosome is the platform for internal daughter budding as revealed by a Nek1 kinase mutant
Authors: Chen Chun-Ti , Gubbels Marc-Jan
Published: June 2013

The pathology and severity of toxoplasmosis results from the rapid replication cycle of the apicomplexan parasite Toxoplasma gondii. The tachyzoites divide asexually through endodyogeny, wherein two daughter cells bud inside the mother cell. Before mitosis is completed, the daughter buds form around the duplicated centrosomes, and subsequently elongate to serve as the scaffold for organellogenesis and organelle partitioning. The molecular control mechanism of this process is poorly understood. Here, we characterized an ortholog of NIMA-related kinase (Nek) in T. gondii identified in a chemical mutagenesis screen. A temperature sensitive mutant, V-A15, possesses a Cys316Arg mutation in TgNek1 (a novel mutant allele in Neks), which is responsible for growth defects at the restrictive temperature. Phenotypic analysis of V-A15 indicated that TgNek1 is essential for centrosome splitting, proper formation of daughter cells, and faithful segregation of genetic material. In vitro kinase assays showed that the mutation abolishes the kinase activity of TgNek1. TgNek1 is recruited to the spindle pole prior to mitosis and localizes to the duplicated centrosomes on the face of the spindle poles in a cell-cycle-dependent manner. Mutational analysis of the activation loop suggests localization and activity are spatio-temporally regulated by differential phosphorylation. Collectively, our results identified a novel temperature sensitive allele for a Nek kinase, which in Toxoplasma highlights its essential function in centrosome splitting. Moreover, these results conclusively show for the first time that Toxoplasma bud assembly is facilitated by the centrosome since defective centrosome splitting results in single daughter cell budding.
TEM4 is a junctional RhoGEF required for cell-cell adhesion, monolayer integrity, and barrier function
Authors: Ngok Siu P. , Geyer Rory , Kourtidis Antonis , Mitin Natalia , Feathers Ryan , Der Channing , Anastasiadis Panos Z.
Published: June 2013

Signaling events mediated by Rho family GTPases orchestrate cytoskeletal dynamics and cell junction formation. The activation of Rho GTPases is tightly regulated by guanine nucleotide exchange-factors (GEFs). In this study, we identified a novel Rhospecific GEF called TEM4 (Tumor Endothelial Marker 4) that associates with multiple members of the cadherin-catenin complex and with several cytoskeleton-associated proteins. Depending on confluence, TEM4 localized to either actin stress fibers, or areas of cell-cell contact. The junctional localization of TEM4 was independent of actin binding. Depletion of endogenous TEM4 by shRNAs impaired Madin-Darby Canine Kidney (MDCK) and Human Umbilical Vein Endothelial Cell (HUVEC) cell junctions, disrupted MDCK acini formation in 3D culture, and negatively affected endothelial barrier function. Together, our findings implicate TEM4 as a novel and critical junctional RhoGEF that regulates cell junction integrity and epithelial and endothelial cell function.
microRNA regulation of skin pigmentation in fish
Authors: Yan Biao , Liu Ban , Zhu Chang-Dong , Li Kang-Le , Yue Li-Jia , Zhao Jin-Liang , Gong Xiao-Ling , Wang Cheng-Hui
Published: June 2013

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play crucial roles in numerous biological processes. However, the role of miRNAs in skin color determination in fish has not been completely determined. Here, we identified that 13 miRNAs are differentially expressed between red and white skin. The analysis of miRNA spatial and temporal expression patterns suggests that miR-429 is potential regulator of skin pigmentation. miR-429 silencing results in a obvious change in skin pigmentation. Bioinformatics analysis and luciferase reporter assay shows that miR-429 directly regulates Foxd3 expression by targeting its 3′ untranslated (3′-UTR) region. miR-429 silencing leads to a significant increase in Foxd3 expression in vivo, thereby repressing the transcription of MITF and its downstream genes such as TYR, TYRP1, or TYRP2. These findings would provide a novel insight into the determination of skin color in fish.
Phosphorylation of Crm1 by CDK1-cyclin B promotes Ran-dependent mitotic spindle assembly
Authors: Wu Zhige , Jiang Qing , Clarke Paul R. , Zhang Chuanmao
Published: June 2013

Mitotic spindle assembly in animal cells is orchestrated by a chromosome-dependent pathway that directs microtubule stabilization. RanGTP generated at chromosomes releases spindle assembly factors from inhibitory complexes with importins, the nuclear transport factors that facilitate protein import into the nucleus during interphase. In addition, the nuclear export factor Crm1 has been proposed to act as a mitotic effector of RanGTP in a converse manner through the localized assembly of protein complexes on the mitotic spindle, notably at centrosomes and kinetochores. It has been unclear, however, how the functions of nuclear transport factors are controlled during mitosis. Here, we report that human Crm1 is phosphorylated at serine 391 in mitosis by CDK1-cyclin B. Expression of Crm1 with serine 391 mutated to either non-phosphorylated or phosphorylation-mimicking residues indicates that phosphorylation directs the localization of Crm1 to the mitotic spindle and facilitates spindle assembly, microtubule stabilization and chromosome alignment. We show that phosphorylation of Crm1 at serine 391 enhances its RanGTP-dependent interaction with RanGAP1-RanBP2 and promotes their recruitment to the mitotic spindle. These results show that phosphorylation of Crm1 controls its molecular interactions, localization and function during mitosis, providing a novel mechanism for the control of mitotic spindle assembly by CDK1-cyclin B. We propose that the Ran GTPase system is controlled during mitosis through the selection of specific molecular interactions by protein phosphorylation.
Notch signaling at a glance
Authors: Hori Kazuya , Sen Anindya , Artavanis-Tsakonas Spyros
Published: June 2013

Cell–cell interactions define a quintessential aspect of multicellular development. Metazoan morphogenesis depends on a handful of fundamental, conserved cellular interaction mechanisms, one of which is defined by the Notch signaling pathway. Signals transmitted through the Notch surface receptor have a unique developmental role: Notch signaling links the fate of one cell with that of a cellular neighbor through physical interactions between the Notch receptor and the membrane-bound ligands that are expressed in an apposing cell. The developmental outcome of Notch signals is strictly dependent on the cellular context and can influence differentiation, proliferation and apoptotic cell fates. The Notch pathway is conserved across species (Artavanis-Tsakonas et al., 1999; Bray, 2006; Kopan and Ilagan, 2009). In humans, Notch malfunction has been associated with a diverse range of diseases linked to changes in cell fate and cell proliferation including cancer (Louvi and Artavanis-Tsakonas, 2012). In this Cell Science at a Glance article and the accompanying poster we summarize the molecular biology of Notch signaling, its role in development and its relevance to disease.
Ca2+ signalling early in evolution – all but primitive
Authors: Plattner Helmut , Verkhratsky Alexei
Published: June 2013

Early in evolution, Ca2+ emerged as the most important second messenger for regulating widely different cellular functions. In eukaryotic cells Ca2+ signals originate from several sources, i.e. influx from the outside medium, release from internal stores or from both. In mammalian cells, Ca2+-release channels represented by inositol 1,4,5-trisphosphate receptors and ryanodine receptors (InsP3R and RyR, respectively) are the most important. In unicellular organisms and plants, these channels are characterised with much less precision. In the ciliated protozoan, Paramecium tetraurelia, 34 molecularly distinct Ca2+-release channels that can be grouped in six subfamilies, based on criteria such as domain structure, pore, selectivity filter and activation mechanism have been identified. Some of these channels are genuine InsP3Rs and some are related to RyRs. Others show some – but not all – features that are characteristic for one or the other type of release channel. Localisation and gene silencing experiments revealed widely different – yet distinct – localisation, activation and functional engagement of the different Ca2+-release channels. Here, we shall discuss early evolutionary routes of Ca2+-release machinery in protozoa and demonstrate that detailed domain analyses and scrutinised functional analyses are instrumental for in-depth evolutionary mapping of Ca2+-release channels in unicellular organisms.
Melanoma-associated mutations in protein phosphatase 6 cause chromosome instability and DNA damage due to dysregulated Aurora-A
Authors: Hammond Dean , Zeng Kang , Espert Antonio , Bastos Ricardo Nunes , Baron Ryan D. , Gruneberg Ulrike , Barr Francis A.
Published: June 2013

Mutations in the PPP6C catalytic subunit of protein phosphatase 6 (PP6) are drivers for the development of melanoma. Here we analyse a panel of melanoma-associated mutations in PPP6C and find that these generally compromise assembly of the PP6 holoenzyme and catalytic activity towards a model substrate. Detailed analysis of one mutant, PPP6C-H114Y, in both primary melanoma and engineered cell lines reveals it is destabilized and undergoes increased turnover by the proteasome. Global analysis of phosphatase substrates by mass spectrometry identifies the oncogenic kinase Aurora-A as the major PP6 substrate dysregulated under these conditions. Accordingly, cells lacking PPP6C or carrying the PPP6C-H114Y allele have elevated Aurora-A kinase activity, and display chromosome instability with associated Aurora-A dependent micronucleation. Chromosomes mis-segregated to these micronuclei are preferentially stained by the DNA damage marker γ-H2AX, suggesting loss of PPP6C promotes both chromosome instability (CIN) and DNA damage. These findings support the view that formation of micronuclei rather than CIN alone explains how loss of PPP6C, and more generally mitotic spindle and centrosome defects, can act as drivers for genome instability in melanoma and other cancers.
Late endosomal transport and tethering are coupled processes controlled by RILP and the cholesterol sensor ORP1L
Authors: van der Kant Rik , Fish Alexander , Janssen Lennert , Janssen Hans , Krom Sabine , Ho Nataschja , Brummelkamp Thijn , Carette Jan , Rocha Nuno , Neefjes Jacques
Published: June 2013

Late endosomes and lysosomes are dynamic organelles that constantly move and fuse to acquire cargo from early endosomes, phagosomes and autophagosome. Defects in lysosomal dynamics cause severe neurodegenerative and developmental diseases such as Niemann-Pick Type C disease and ARC syndrome, yet little is know about regulation of late endosomal fusion in a mammalian system. Mammalian endosomes destined for fusion need to be transported over very long distances before they tether to initiate contact. Here we describe that lysosomal tethering and transport are combined processes co-regulated by one multi-protein complex; RAB7-RILP-ORP1L. We show that RILP directly and concomitantly binds the tethering HOPS complex and the p150glued subunit of the dynein motor. ORP1L then functions as a cholesterol-sensing switch controlling RILP-HOPS-p150Glued interactions. We show that RILP and ORP1L control Ebola virus infection, a process dependent on late endosomal fusion. By combining recruitment and regulation of both the dynein motor and HOPS complex into a single multiprotein complex, the RAB7-RILP-ORP1L complex efficiently couples and times microtubule minus-end transport and fusion, two major events in endosomal biology.
Novel Environmentally Friendly Inorganic Blue Pigments Based on Amorphous Tungsten Oxyphosphate
Authors: Wendusu  , Hosoya Ayaka , Masui Toshiyuki , Imanaka Nobuhito
Published: June 2013

Novel environmentally friendly inorganic blue pigments based on amorphous tungsten oxyphosphate, (W1−xLnx)OP2O7−δ (0.10 ≤ x ≤ 0.29; Ln = La, Eu, Gd, Y, and Lu) were successfully synthesized, and their color properties were characterized. Among the samples, (W0.76Eu0.24)OP2O7−δ shows the most brilliant blue color. The b* value corresponding to blue chromaticity of the (W0.76Eu0.24)OP2O7−δ pigment was −25.2, which exceeds that of a commercially available iron hexacyanoferrate pigment (Prussian blue, b* = −15.6). Since the present (W0.76Eu0.24)OP2O7−δ pigment consists of only nontoxic and safe elements, it could be an effective alternative to conventional blue pigment.
Optimum Particle Size of ZnO for Dye-sensitized Solar Cells
Authors: Sakai Nobuya , Usui Ryo , Murakami Takurou N
Published: June 2013

The relationship between the size of ZnO particles in porous semiconductor electrodes and their photovoltaic performance for dye-sensitized solar cells (DSSCs) was investigated. The DSSCs employing 40 nm ZnO particles showed the best power conversion efficiency among those based on particles in the size range 20 nm to 2 µm. The cell performance drastically changed further upon TiCl4 post-treatment of the ZnO layer, and a treatment time of more than 20 min was found necessary to improve the performance.
Hydrosilylation of Various Multiple Bonds by a Simple Combined Catalyst of a Tungstate Monomer and Rhodium Acetate
Authors: Itagaki Shintaro , Sunaba Hanako , Kamata Keigo , Yamaguchi Kazuya , Mizuno Noritaka
Published: June 2013

In the presence of a simple combined catalyst of a tungstate monomer (TBA2WO4, TBA: tetra-n-butylammonium) and rhodium acetate (Rh2(OAc)4), hydrosilylation of various types of substances including ketone, aldehyde, carbon dioxide, alkene, nitrile, and furan derivatives efficiently proceeded, affording the corresponding hydrosilylation products in moderate to high yields (≥63% yields). In addition, the present system was also applicable to the one-pot reduction of benzamide to benzylamine (95% yield).
Helix-sense-selective Polymerization of 3,5-Bis(hydroxymethyl)phenylacetylene Connected with a Rigid and π-Conjugated Substituent
Authors: Shi Zhichun , Murayama Yoshinori , Kaneko Takashi , Teraguchi Masahiro , Aoki Toshiki
Published: June 2013

An achiral 3,5-bis(hydroxymethyl)phenylacetylene connected with a rigid and π-conjugated substituent was polymerized using a rhodium (Rh) complex catalyst in the presence of chiral 1-phenylethylamines. The circular dichroism (CD) spectra of the polymers indicated that an excess of one-handed helical polyacetylene backbone was induced by helix-sense-selective polymerization under the asymmetric conditions despite the achiral monomer. The split-type-induced CD signals at 300 nm were attributed to the chromophore including the conjugated side group since the signal appeared at a longer wavelength than the poly[3,5-bis(hydroxymethyl)phenylacetylene] without conjugated substituent.
Three New Pteridines from the Leech Whitmania pigra
Authors: Li Tao , Wang Guo-Cai , Wang Chun-Hua , Ye Wen-Cai
Published: June 2013

Chemical investigation on the dried material of the leech Whitmania pigra has led to the isolation of three new pteridines, including two new lumazines bearing a thieno[3,2-g]lumazine skeleton, whitmanines A and B (1 and 2) and a new pterin, 5,8-dimethylleucopterin (3). Their structures were established mainly by spectroscopic methods, especially HR-ESI-MS and NMR techniques.
Impacts of Dibenzo- and Dithieno-fused Structures at the b, g Bonds in the BODIPY Skeleton
Authors: Shimogawa Hiroyuki , Mori Haruki , Wakamiya Atsushi , Murata Yasujiro
Published: June 2013

Dibenzo[b,g]-fused and dithieno[b,g]-fused BODIPY derivatives were synthesized, and the electronic effects of the introducing dibenzo- and dithieno-fused structures at both of the b and g bonds in the BODIPY skeleton were investigated. Electrochemical and photophysical measurements demonstrated that these structural modifications effectively enhance the electron-accepting ability of the BODIPY skeleton leading to the red-shifted absorption.
Robert Robertson, FRS (1742–1829): physician to the Royal Hospital, Greenwich, 18th-century authority on ‘fever’, and early practitioner in care of the elderly
Authors: Cook G C
Published: June 2013

Robert Robertson was born in Scotland and trained to be a surgeon. In 1760, he served briefly on a whaling ship and then entered the Royal Navy. He subsequently had many postings, several of them to the tropics. He recorded his observations on fevers, scurvy and other illnesses. After 23 years of active service, he retired to private practice in Hampshire. However, later he rejoined the service and was appointed physician to the Royal Hospital, Greenwich, where later he was made a Director. During this period, he addressed the problems of illness after the days of active service. Robertson was thus an early practitioner in the care of the elderly. He retired in 1807 and died at Greenwich at the age of 87.
Dr James Currie (1756–1805): Liverpool physician, campaigner, hydrotherapist and man of letters
Authors: Halliday Stephen
Published: June 2013

James Currie was born and educated in Scotland but spent most of his professional life in Liverpool, where, as physician to the Liverpool Infirmary, he campaigned against the unsanitary living conditions in the rapidly growing port. He was an early advocate of water cures for fever and other maladies, on which subject he carried out experiments and published a seminal work. He was a pioneer in the use of the clinical thermometer. He was also an early advocate of the abolition of slavery and a man with literary and scientific interests, which brought him into contact with many of his most distinguished contemporaries. These included Erasmus Darwin (1731–1802), William Wilberforce (1759–1833), Sir Walter Scott (1771–1832), Sir Joseph Banks (1743–1820) and Robert Burns (1759–96), of whose poetry Currie was the first editor. He died in August 1805 at Sidmouth in Devon, whose parish church carries his memorial.
Post-Peninsular War activities of Sir James McGrigor (1771–1858), Wellington's Director-General of the Army Medical Department
Authors: Kaufman M H
Published: June 2013

James McGrigor (1771–1858) entered the Army Medical Department in September 1793, when he purchased a Surgeoncy in De Burgh's regiment. He transferred to the Blues (the Royal Horse Guards) in 1804 and shortly afterwards his organizational skills were recognized by the Duke of York. In 1811, he recommended McGrigor to Wellington, who commanded the British Forces in the Peninsula, and McGrigor joined Wellington in January 1812. As a result of his outstanding achievements during the Peninsular War, McGrigor was knighted in 1814. He later played a critical role in the post-Peninsular War Army by elevating the academic standard of the intake of medical officers as well as improving the standard of those who wished to gain promotion in the service. He established an extensive Anatomy, Pathology and Natural History Museum and the reference library at Fort Pitt at Chatham in Kent. He retired at the beginning of 1851, and died in London in April 1858, aged 87. In 1863, the museum collections were moved initially to the Army Medical School at Netley. At a later date these collections were dispersed and their present whereabouts are unknown. A significant proportion of his library is presently located in the Contemporary Medical Archives Centre on permanent loan in the library of the Wellcome Institute for the History of Medicine.
>Leading a double life in 17th-century Oxford: Ralph Bathurst (1620–1704), physician–physiologist and cleric
Authors: Guy Jean M
Published: June 2013

Ralph Bathurst spent most of his working life in Trinity College, Oxford. Strongly influenced by William Harvey, he was a friend and colleague of Thomas Willis, Robert Boyle and many other eminent experimentalists. His intended career as an Anglican priest and theologian was frustrated during the Commonwealth. Instead, he trained as a physician and practised in Abingdon in Berkshire and in the Navy. His examination papers for the degrees of Bachelor and Doctor of Medicine survived and were printed many years after his death. This paper, summarizing the three Latin lectures on respiration given for his doctoral degree in 1654, throws light on the physiological research carried out in Oxford at that time. The lectures included clinical observations, the results of experiments performed by himself and others, and speculations on the chemistry of air in the era before Joseph Priestley.
Sir William Dunn (1833–1912): the man, his trust and his legacy to science and medicine
Authors: Sidebottom Eric , Paul Alison
Published: June 2013

William Dunn had no direct connections with medicine. He belonged to that Victorian generation of Scottish pioneers who went overseas to make their fortunes and, yet, devoted their money to numerous charitable purposes, mainly at home in the UK. His family origins were modest; born in Paisley, near Glasgow on 1 September 1833, he died in 1912 with an estate valued at £1.3 million. His fortune was made from a large worldwide trading empire with roots in South Africa, where he emigrated as a young man of 19 – but later controlled from London. In his will, dated 4 November 1908, the key clause was ‘to advance the cause of Christianity, to benefit children and young people, to support hospitals and alleviate human suffering, to encourage education and promote emigration’. After making provision for about half the total, he left the remainder in the hands of trustees. They allotted about 120 small sums to hospitals, nursing homes, orphanages and like institutions, but then decided that larger projects would be more likely to be permanent memorials to Sir William. After consulting the President of the Royal Society, Sir William Hardy, and the Secretary of the Medical Research Committee, Sir Walter Fletcher, the trustees gave £210,000 in 1920 to Sir Frederick Gowland Hopkins in biochemistry in Cambridge and £100,000 in 1922 to Professor Georges Dreyer in pathology in Oxford. Between them, these two laboratories have ‘spawned’ nine Nobel Prize winners. The ‘alleviation of human suffering’ achieved would surely have pleased Sir William and his trustees.
Walter Edward Dandy (1886–1946)
Authors: Pearce J M S
Published: June 2013

Dandy was a leading light in the initiation and development of neurosurgery, not only in his native America but also throughout the world. This paper attempts briefly to outline his main achievements. After a turbulent relationship with Cushing he emerged as a brilliant, if vain, surgeon and investigator, based mainly at Johns Hopkins. He initiated air ventriculography and effected original studies on cerebrospinal fluid formation and circulation. The Dandy–Walker syndrome, surgery for aneurysms and cerebellopontine angle tumours were but a few areas where he made his mark and left a lasting legacy of neurosurgical endeavour.
The Women's Hospital Corps: forgotten surgeons of the First World War
Authors: Geddes Jennian F
Published: June 2013

Under the leadership of the former militant suffragists Flora Murray and Louisa Garrett Anderson, a group of women doctors calling themselves the Women's Hospital Corps (WHC) successfully ran two military hospitals in France from September 1914 to January 1915. In 1915 the War Office invited them to run a military hospital in London where large numbers of new beds were being created. It gave them former workhouse premises in Covent Garden, which they transformed into a 573-bed hospital, staffed and administered entirely by women. The Endell Street Military Hospital, the first hospital in the UK established for men by medical women, was open from May 1915 to December 1919; in that time, its doctors saw 26,000 patients and performed over 7000 major operations. A key feminist organization of the First War, the WHC has largely been forgotten, partly because of its relatively small size and partly because of its anomalous status as a female-run hospital under the direct patronage of the War Office.
Dr Frederick Knight Hunt (1814–54) re-visited: medical man and journalist
Authors: Hunt John L
Published: June 2013

This paper studies Knight Hunt's career after he lost control of the Medical Times, and shows how he was brought to the notice of Charles Dickens who made him a sub-editor on the Daily News in 1845 and subsequently selected him as a pivotal contributor to Household Words, a post he gave up only when he became editor of the newspaper in 1851.
William Pepper Jr, MD (1843–1898): portrait of a nineteenth-century medical educator
Authors: Re Vincent Lo , Bellini Lisa M
Published: June 2013

Dr William Pepper Jr was a prominent Philadelphia physician whose contributions to medicine in the late 19th century are not widely known. As a young physician he rose in stature rapidly due to his abilities as a diagnostician, teacher, writer and researcher. His primary interest, however, was to improve the education of physicians. He orchestrated the creation of America's first university-controlled teaching hospital, the Hospital of the University of Pennsylvania, enabling substantial improvements in clinical training. Pepper later became Provost of the University of Pennsylvania and ambitiously transformed the curriculum of the medical school, providing greater basic science and clinical training. He also worked to establish several institutes and museums in Philadelphia in order to promote academic pursuits, particularly in medicine. William Pepper Jr was one of the 19th century's foremost medical educators and his accomplishments helped reshape the way medicine was taught throughout the United States.
Georges Dreyer (1873–1934) and a forgotten episode of respiratory physiology at Oxford
Authors: West John B , Sidebottom Eric
Published: June 2013

Georges Dreyer was the first Professor of Pathology at Oxford University and he held this post from 1907 to 1934. Although his main research interests were in bacteriology and immunity, he made important contributions to respiratory physiology, but these have been almost completely forgotten. He developed a new apparatus for administering low oxygen mixtures to test the effects of hypoxia in airmen during World War I, developed a high successful oxygen delivery system, was responsible for the first low-pressure chamber in a UK academic institution, and carried out some physiological measurements in the chamber that were years ahead of their time. His chamber was also used by a group from Cambridge and Turin, Italy for a series of important physiological studies. In spite of these contributions, almost nobody who works in respiratory physiology today, even in Oxford, recognizes the name of Dreyer.
The Grellier twins, Norman (1886–1949) and Bernard (1886–1957), radiologists of East Sussex
Authors: Kenney Ian J
Published: June 2013

Identical twins Bernard and Norman Grellier (born Epsom, 1886) attended Epsom College before entering Dental School at the Royal Dental Hospital of London in 1904, graduating in 1910. Then they trained in medicine at Charing Cross Hospital. Bernard graduated in 1913 and Norman in 1915. In 1915 they joined the Royal Army Medical Corps (RAMC), serving to the end of World War I (WWI), each being awarded the Military Cross for gallantry. After WWI, they trained as radiologists and moved to St Leonards-on-Sea in West Sussex, taking up Consultant posts at the Royal East Sussex Hospital and the Municipal Hospital in Hastings, and the Eversfield Chest Hospital in St Leonards. In 1940 they rejoined the RAMC as radiologists, serving throughout World War II. They remained unmarried, devoted to each other, to their practice and to their loves of model engineering and flying, the latter nearly causing their deaths in an air crash in 1936.
Eponymous, anonymous: Queen Anne's sign and the misnaming of a symptom
Authors: Lane Furdell Elizabeth
Published: June 2013

Tracing the historical origins of an eponymous medical sign can be fraught with dilemmas, particularly when the evidence for the naming comes from portraiture. Laterally truncated eyebrows, a sign of hypothyroidism, came to be associated with Anne of Denmark (1574–1619), James I's Queen Consort, likely because a contemporaneous portrait of her by Paul van Somer shows a woman with fair and abbreviated brows. Extant medical information on Anne, however, does not support a diagnosis of hypothyroidism nor does her very active queenship point to such an affliction. Nonetheless, some authorities continue to employ the label, invoking Queen Anne's painted likeness as proof that she was goitrous and manifested the characteristically shortened eyebrows of those with a deficiency of thyroid activity.
Albert Calmette (1863–1933) and Camille Guérin (1872–1961): the C and G of BCG vaccine
Authors: Hawgood Barbara J
Published: June 2013

Early in his medical career, Albert Calmette showed a remarkable aptitude for bacteriology and, in 1891, he opened the first daughter Pasteur Institute in Saigon, French Indochina at the request of Louis Pasteur. In 1894, at the Pasteur Institute in Paris, Calmette succeeded in developing an antiserum to cobra venom and so initiated antivenomous serotherapy. In 1895 Calmette was asked to found a second daughter, Pasteur Institute in Lille. Soon he was joined by the young veterinarian, Camille Guérin, and so began a unique partnership, the two men striving to free people from the dreadful scourge of tuberculosis. Investigating the intestinal route of tuberculous infection, Calmette and Guérin began to grow Mycobacterium tuberculosis bovis in a beef bile-glycerine medium. With continuous replanting of the culture in this medium (from 70 to 235 times), an attenuated bacillus of fixed properties was discovered; this Calmette called Bacille-Calmette-Guérin (BCG). Exhaustive testing of BCG showed its safety and effectiveness in protecting young animals against tuberculosis. In 1924 vaccination of newborn infants with BCG began in France and spread worldwide.
Dr Jacob Mackiewicz (1887–1966) and his sign
Authors: Ohry Avi
Published: June 2013

Dr Jacob Mackiewicz, a Jewish-Polish neurologist, described the cruralis phenomenon related to injury of the femoral nerve or of the fourth lumbar root. In 1912, only one year after graduation maxima cum laude from Moscow University, the 25-year-old Dr Jacob Mackiewicz described the cruralis phenomenon, regarded in the German and Slavic medical literature as the Mackiewicz sign:‘the patient lies prone, the examiner lifts the thigh in one hand, with the other hand, bends the patient's knee slowly; this manoeuvre causes severe pain in the anterior part of the thigh and over the groin. This manoeuvre indicates a femoral nerve injury’.
Rudolph Weigl (1883–1957) – a scientist in Poland in wartime Plus ratio quam vis
Authors: Wincewicz Andrzej , Sulkowska Mariola , Sulkowski Stanislaw
Published: June 2013

Rudolph Weigl gained a high estimation for his spectacular invention of the first efficient vaccine against typhus fever. Although born a German native speaker, he changed into a great Pole with Polish education and upbringing in a patriotic atmosphere. His scientific career developed in the Universities of Lvov, Cracow and Poznan. For him, academic employment was a constant exploration of practical truths and a response to human needs, and this remained a deep obligation during his lifetime. His vaccine saved millions, particularly during World War II. Despite many nominations, he was never awarded the Nobel Prize.
The price of meetings with Charles Dickens (1812–70)
Authors: Hunt John L
Published: June 2013

The main theme of this article is an analysis of the way in which meetings with Leigh and Knight Hunt may have influenced Charles Dickens' portrayal of Harold Skimpole in Bleak House.
John MacCulloch, MD (1773–1835): a dedicated geologist
Authors: Hull Gillian
Published: June 2013

The teaching in Scottish medical schools in the second half of the 18th century had a reputation that stretched far beyond Britain. Edinburgh attracted students not only for its high academic standards but also for its freedom from religious constraints and its developing interest in the sciences. John MacCulloch was taught at Edinburgh by Joseph Black (1728–99) who had chosen chemistry as a career rather than medicine. Already MacCulloch's enquiring mind ranged over many subjects.
The surgeon, the Countess, her husband and his lover: John Hunter (1728–93) and the Countess of Strathmore (1749–1800)
Authors: Moore Wendy
Published: June 2013

John Hunter (1728–93) was one of the most popular and controversial surgeons of the 18th century. He treated the celebrities of his day including William Pitt the younger, Adam Smith and David Hume. Today he is acclaimed for his pioneering approach as the founder of scientific surgery. Yet a hitherto unknown aspect of his work – looking after the illegitimate offspring of one of his patients – has only recently come to light in some letters transcribed in archives at Glamis Castle in Scotland.
Rustom Jal Vakil and the saga of Rauwolfia serpentina
Authors: Goenka Ajit H
Published: June 2013

Dr Rustom Jal Vakil was India's pioneer in cardiology. He introduced the discipline of cardiology in his country. His mixture of clinical acumen, research and writing has survived him. Through his work with an ancient Indian folk remedy, Rauwolfia serpentina, he ushered in the modern era of effective pharmacotherapy of hypertension. His work was particularly significant since it galvanized other workers into finding more effective agents for the treatment of hypertension. He is remembered fondly by his acquaintances as an unassuming man in whom a multitude of choicest qualities blended seamlessly with each other.
Albert Eckstein (1891–1950): modernizer of Turkey's paediatrics in exile
Authors: Akar Nejat , Reisman Arnold , Oral Aysu
Published: June 2013

This paper provides a historical perspective on Ordinarius Professor Albert Eckstein. He was the architect of modern paediatrics in Turkey. The year 2005 was the 55th anniversary of Professor Albert Eckstein's death and the 60th anniversary of the founding of the Paediatric Clinics at Ankara University, where he served for five years as the founding director while in forced exile from Nazi Germany. This is a tale of an individual caught at the crossroads and in the crossfire of history. His native land was in the throes of discarding him. His life was saved because (to him) an alien country was discarding a societal culture inherited from the Ottomans. Turkey recognized the need to modernize its society. The Nazis came to power. Albert Eckstein, a noted German paediatrician, was Jewish.
Neuropathology in Germany during World War II: Julius Hallervorden (1882–1965) and the Nazi programme of ‘euthanasia’
Authors: Hughes J T
Published: June 2013

In Germany during World War II, more than 120,000 handicapped children and adults were murdered for the convenience of the State. To gain scientific knowledge, the brains of many of these patients were examined by German neuropathologists. Some 698 of these specimens were examined in the Kaiser-Wilhelm-Institut für Hirnforschung in Berlin-Buch by Julius Hallervorden whose career is reviewed together with that of his superior, Hugo Spatz. Hallervorden also oversaw the examination of cases of mental handicap by W-J Eiche at a laboratory at the Hospital Brandenburg-Gorden. Also in Berlin was Berthold Ostertag, neuropathologist at the Rudolf-Virchow-Hospital, who examined cases from the Children's Ward at Wiesengrund. Smaller but significant numbers of brains were examined in Munich, Heidelberg, Hamburg and Schleswig. Some brains of similar origin were examined in Vienna and in Lubliniecz. Jürgen Peiffer has estimated that German neuropathologists examined 2097 brains arising from the Nazi Programme of ‘Euthanasia’.
Francis Thompson (1859–1907): a medical truant and his troubled heart
Authors: Breathnach Caoimhghin S
Published: June 2013

Summary

Francis Thompson was born in 1859 in Preston and grew to manhood in Ashton-under-Lyne in Lancashire. After six years registered as a medical student at Owens College, Manchester, he set off for London to retrace the footsteps of Thomas De Quincey (1785–1859). His early experience in London followed closely that of the earlier English Opium Eater until he was rescued by Wilfrid Meynell (1852–1948) who recognized his nascent literary flair. Thompson's poetry earned him respect and reputation and his prose brought him a reasonable income, but he never weaned himself from laudanum and he died of tuberculosis in 1907. Not every truant is honoured by a lapidary inscription in his alma mater, even though he may be overlooked in an arbitrary census.
Dr Percy Charles Edward d'Erf Wheeler (1859–1944): a notable medical missionary of the Holy Land
Authors: Yaron Perry , Efraim Lev
Published: June 2013

Dr Percy Charles Edward d'Erf Wheeler, a medical missionary of the London Society for Promoting Christianity Amongst the Jews, spent 24 years (1885–1909) as head of the English medical institution in Jerusalem. Wheeler dedicated the years he served in Palestine to promote the medical condition of the Jews as a means of missionary work. The most significant of his achievements was his leading role in the founding of the new British Hospital for the Jews in Jerusalem, the flagship of the British presence in Palestine, to be inaugurated in 1897.
Surgeon James Inderwick (d. 1815) and United States Brig Argus in the War of 1812–14
Authors: Agnew Robin
Published: June 2013

In June 1813, during the War of 1812–1814 with America, the US Brig Argus embarked from New York with orders to raid British coastal commerce, causing panic in the British and Irish shipping trade. On the morning of 14 August, HM Brig Pelican engaged Argus off St David's Head. After a fierce battle, Argus surrendered. Her surgeon was James Inderwick whose journal tells of his work as a surgeon in the US Navy.
The Cost-Effectiveness of Prenatal Detection for Congenital Heart Disease Using Telemedicine Screening
Authors: Mistry Hema , Gardiner Helena M
Published: June 2013

We estimated the longer-term cost-effectiveness of using telemedicine screening for prenatal detection of congenital heart disease (CHD). One hospital in south-east England with a telemedicine service was connected to a fetal cardiology unit in London. A UK health service perspective was adopted. Evidence on costs and outcomes for standard-risk pregnant women during the antenatal period was based on patient-level data. Extrapolation beyond the end of the study (just after delivery) was carried out for the lifetime of children born with and without CHD. Expert opinion and data from published sources was used to populate a decision model. Future costs and benefits were discounted. The main outcome was quality-adjusted life years (QALYs) and results were expressed as cost per QALY gained. Various one-way sensitivity analyses were conducted. The model showed that offering telemedicine screening by specialists to all standard-risk pregnant women was the dominant strategy (i.e. cheaper and more effective). The sensitivity analyses found that the model was robust, and that telemedicine remained the most cost-effective strategy. The study showed that it would be cost-effective to provide telemedicine examinations as part of an antenatal screening programme for all standard-risk women.
Use of a homecare electronic health record to find associations between patient characteristics and re-hospitalizations in patients with heart failure using telehealth
Authors: Radhakrishnan Kavita , Jacelon Cynthia S , Bigelow Carol , Roche Joan , Marquard Jenna , Bowles Kathryn H
Published: June 2013

Data from homecare electronic health records were used to explore the association of patient characteristics with re-hospitalizations of patients with heart failure (HF) during a 60-day period of telemonitoring following hospital discharge. Data from 403 Medicare patients with HF who had used telehealth from 2008 to 2010 were analysed. There were 112 all-cause (29%) and 73 cardiac-related (19%) re-hospitalizations within 60 days of the start of telemonitoring. In adjusted analyses, the patients’ number of medications and type of cardiac medications were significantly ( P < 0.05) associated with an increased risk of re-hospitalization. After stratifying the sample by illness severity, age and gender, other significant ( P < 0.05) predictors associated with an increased risk of all-cause and cardiac re-hospitalization were psychiatric co-morbidity, pulmonary and obesity co-morbidities within gender, beta blocker prescription in females and primary HF diagnosis in the oldest age stratum. The study's findings may assist homecare agencies seeking to allocate resources without compromising patient care.
Let's All Jump on the Ultrasound Bandwagon: Further Debate on the Use of Ultrasound
Authors: Edwards Hazel
Published: June 2013

No imaging technique is more popular or more in demand than ultrasound. But should it be considered a specialist technique to be employed only by highly trained professionals or as a readily available tool to be used by many? This paper will discuss some of the implications of having ultrasound performed by a range of individuals and will emphasize the importance of training and regulation.
Prenatal Diagnosis of Anterior Encephalocele
Authors: Witters Ingrid , Van Robays Johan , Gyselaers Wilfried , Fryns Jean-Pierre
Published: June 2013

We describe a prenatal diagnosis at 16 weeks of an anterior encephalocele and discuss the possibilities for prenatal diagnosis and differential diagnosis of this rare fetal malformation.
Musculoskeletal Ultrasound: Audit of Sonographer Reporting
Authors: Riley Sara J , Groves C J , Chandramohan M
Published: June 2013

Musculoskeletal (MSK) ultrasound performed by non-medical practitioners is a developing practice. The aim of this paper is: (1) to audit an experienced sonographer's (SJR) performance after one year's independent reporting against two experienced MSK radiologists (CJG, MC); and (2) to establish an audit standard against which such role development might be contrived. Images and reports from 250 MSK ultrasound examinations performed by a sonographer (SJR) were reviewed independently by two consultant MSK radiologists (CJG and MC). The examinations were graded for discrepancy, e.g. grade 1 – agree with the sonographer report; grade 2 – minor discrepancy unlikely to alter patient care; grade 3 – potentially significant discrepancy; grade 4 – definite, significant discrepancy likely to have adverse consequences for patient care. Two of 250 (0.8%) cases were excluded. Both radiologists agreed completely with the sonographer (grade 1) in 235 of the 248 cases (94.8%). In 13 cases there was discrepancy between the reports of SJR and the radiologists. The discrepancy was grade 2 in six of the 248 cases (2.4%), grade 3 in six of the 248 cases (2.4%) and grade 4 in one of the 248 cases (0.4%). In conclusion, this audit shows a high level of agreement between the sonographer and the consultant MSK radiologist reporting of MSK ultrasound. This level of agreement may set the standard for future quality assurance audit of sonographer MSK reporting.
Out and about
Authors: Williams Norman
Published: June 2013

One of the pleasures and, indeed, privileges of being President of the College is to be invited to participate in regional meetings and visit fellows and members in their own trusts. These visits are extremely informative from my perspective and i hope they are helpful to participants. Of course, they are also hugely enjoyable from a social point of view and i want to take this opportunity to thank my hosts for looking after my colleagues and me so well.