tbuckley/cabot-search huggingface dataset:
Efficient, pH‐Triggered Drug Delivery Using a pH‐Responsive DNA‐Conjugated Gold Nanoparticle
Authors: Lei Song, Vincent H.B. Ho, Chun Chen, Zhongqiang Yang, Dongsheng Liu, Rongjun Chen, Dejian Zhou
Journal: Advanced Healthcare Materials (2012)

A novel drug nanocarrier that offers simple, direct, native form drug loading without involving any chemical modification and/or coupling step has been developed by using a pH-responsive DNA–gold nanoparticle conjugate. It can resist non-specific adsorption of serum proteins upon PEGylation and can provide efficient delivery and pH-triggered release of anticancer drugs to cancer cells, leading to high cytotoxicity. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Processing capacity limits are not explained by storage limits
Authors: Graeme S. Halford, Steven Phillips, William H. Wilson
Journal: Behavioral and Brain Sciences (2001)

Cowan's review shows that a short-term memory limit of four items is consistent with a wide range of phenomena in the field. However, he does not explain that limit, whereas an existing theory does offer an explanation for capacity limitations. Furthermore, processing capacity limits cannot be reduced to storage limits as Cowan claims.
Mallory bodies and intermediate filaments: Of mice and men
Authors: Helmut Denk
Journal: Hepatology (1987)

Livers from 12 mice fed griseofulvin for 4 to 6 months were perfused in situ with a detergent solution to extract lipid membranes leaving the cytoskeleton intact. Seven control mice were similarly studied. After 30 to 120 minutes perfusion, liver samples were examined by scanning electron microscopy and transmission electron microscopy. By light microscopy, Mallory bodies (MBs) were observed in pericentral hepatocytes. These were confirmed by transmission electron microscopy. Intermediate filaments (IFs) were observed in close apposition to MBs. Numerous IFs were seen throughout the cytoplasm. The 3-dimensional organization of the cytoskeleton and MBs were clearly visualized by scanning electron microscopy. The IFs were disorganized in the hepatocytes and formed small MBs in griseofulvin- treated mice. In the case of hepatocytes containing large MBs, there was an apparent decrease in the concentration of IFs. Transition forms of dense networks of IFs between the normal cytoskeleton and the MBs were noted in the cytoplasm between small MBs and the nucleus and also at the cell border. The IFs connected to the nucleus and invaded the MBs. The MBs appeared to form as a result of condensation or collapse of the IFs. Evidence has been accumulating that Mallory body (MB) is a heritable phenotype of hepatocellular carcinoma (HCC) and is closely related to hepatocarcinogenesis in some carcinogen-fed animals. This prompted us to try to evaluate the MB phenomenon in human HCCs, in which its significance remains unclear to date. Whole liver slices were obtained from 28 autopsied livers in which MB-positive HCC was found, and distribution of MBs within the HCC was examined. There were three distribution patterns: clustering, diffuse, and sparse types. The clustering type was the most frequent and was found in 21 of the 28 cases. In this type, there was a formation of groups of the MB-containing cells within the HCC, and the cluster of MB-positive cells was variable in number, size, and shape. There was often a sharp border line between MB-positive clusters and the surrounding MB-negative HCC cell areas where a collision line could occasionally be seen. Some of the MB-containing HCC cells were positive for γ-glutamyl transpeptidase and α-fetoprotein. These data led the authors to speculate that MB-positive HCC cells in human livers are capable of proliferation to form the clusters and that therefore, MBs are expressed as a kind of heritable phenotype in such clusters.
ENDOVASCULAR THERAPY FOR PATIENTS AGED 80 YEARS OR OLDER WITH AORTO-ILIAC LESION
Authors: Shin Okamoto, Osamu iida, Tomoharu Dohi, Masaaki Uematsu, Yoshimitsu Soga, Daizo Kawasaki, Kenji Suzuki, Junichi Tazaki, Daisuke Kamoi, Ryoji Koshida, Yoshiaki Shintani, Michiaki Higashitani, Yusuke Miyashita, Terutoshi Yamaoka, Nobuhiro Suematsu
Journal: Journal of the American College of Cardiology (2012)
The Ki67 proliferation index is a quantitative indicator of clinical risk in mantle cell lymphoma
Authors: Tiemo Katzenberger, Celine Petzoldt, Sylvia Höller, Uwe Mäder, Jörg Kalla, Patrick Adam, M. Michaela Ott, Hans Konrad Müller-Hermelink, Andreas Rosenwald, German Ott
Journal: Blood (2006)
The Use of Blood in the Treatment of Duodenal Fistula
Authors: Peter A. Consales, William T. O'Connell
Journal: New England Journal of Medicine (1944)

EXTERNAL duodenal fistula constitutes a problem of great importance: and if not corrected usually terminates fatally.1 Fortunately, it is a rare complication. Up to 1923 only 61 cases had been reported.2 In a more recent communication by Bartlett and Lowell,3 however, 128 authentic cases were presented in what was believed to be a complete review of the literature from 1865 to 1937. It is apparent that within the last two decades the prevalence of this disease has increased, perhaps owing to the greater number of operative procedures carried out in the right upper quadrant of the abdomen. The mortality is still extremely high. Most authors consistently report an approximate mortality of 50 per cent irrespective of the procedures used, whether medical or surgical.4 Management along conservative measures, however, has considerably reduced the mortality.5 According to Kittelson,6 65 cases treated conservatively had
Treatment of cutaneous calcinosis in limited systemic sclerosis with minocycline
Authors: L P Robertson
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objectives:</b> To evaluate the effect of minocycline as treatment for cutaneous calcinosis in limited cutaneous systemic sclerosis (lcSSc). <b>Methods:</b> Patients with lcSSc who had cutaneous calcinosis causing pain or ulceration, or both, were prescribed minocycline 50 or 100 mg daily regularly in an open label manner between November 1994 and April 2000. At routine clinical follow up the appearance of the calcinosis deposits was assessed clinically and radiographically, and the patients' assessment of the degree of discomfort, size, and frequency of ulceration was recorded. Demographic data, including disease duration, clinical features, and antinuclear antibody (ANA) titres, were also recorded. <b>Results:</b> Nine patients have been treated to date. Eight of the nine patients were ANA positive, five of whom were positive for anticentromere antibodies. Eight patients have shown definite improvement and seven patients continue to receive treatment. The frequency of ulceration and inflammation associated with the calcinosis deposits decreased with treatment. The size of the calcinosis deposits also decreased but was less dramatic than expected. Improvement occurred at the earliest after one month of treatment with a mean (SD) of 4.8 (3.8) months. The mean (SD) length of treatment was 3.5 (1.9) years. An unexpected effect was the darkening of the calcinosis deposits to a blue/black colour. <b>Conclusions:</b> Minocycline may be effective in the control of calcinosis in systemic sclerosis. A low dose only is required and appears to be generally well tolerated. The mechanism of action may be mainly through inhibition of matrix metalloproteinases and anti-inflammatory effects. Calcium binding properties and antibacterial actions may also have a role.
Usefulness of HBV-DNA assayed by hybridization solution for selecting candidates to IFN therapy
Authors: M. Rodríguez, P. Sala, A. Suárez, C.A. Navascués, R. Pérez, S. Riestra, J.L.S. Lombraña, A. Linares, N.G. Sotorrio, L. Rodrigo
Journal: Journal of Hepatology (1991)
Urinary p-nitrophenol as a biomarker of household exposure to methyl parathion.
Authors: Daniel O Hryhorczuk, Mike Moomey, Ann Burton, Ken Runkle, Edwin Chen, Tiffanie Saxer, Jennifer Slightom, John Dimos, Ken McCann, Dana Barr
Journal: Environmental Health Perspectives (2002)

Methyl parathion (MP) is an organophosphate pesticide illegally applied to the interiors of many hundreds of homes throughout the United States by unlicensed pesticide applicators. Public health authorities developed a protocol for investigating contaminated homes and classifying their need for public health interventions. This protocol included environmental screening for MP contamination and 1-day biomonitoring (a.m. and p.m. spot urine samples) of household members for p-nitrophenol (PNP), a metabolite of MP. The variability of urinary PNP excretion under these exposure conditions was unknown. We collected a.m. and p.m. spot urine samples for 7 consecutive days from 75 individuals, who were members of 20 MP-contaminated households in the greater Chicago, Illinois, area, and analyzed them for PNP. We also assessed the ability of the 1-day sampling protocol to correctly classify exposed individuals and households according to their need for public health interventions, assuming that 1 week of sampling (14 urinary PNPs) represented their true exposure condition. The coefficient of variation of log urinary PNPs for individuals over the course of 7 days of a.m. and p.m. sampling averaged about 15%. Adjusting for urinary excretion of creatinine improved reproducibility of urinary PNPs among children but not among adults. The 1-day protocol correctly classified true risk category in 92% of individuals and 85% of households. The data contained in this study can be used to refine what is already a reasonable and effective approach to identifying MP-exposed households and determining the appropriate public health intervention.
Plight of Operating-theatre Technicians
Authors: L. J. Temple
Journal: BMJ (1965)

<b>Background: </b> In adrenomyeloneuropathy (AMN) conventional MRI detects only spinal cord atrophy in the late stages. <b>Objective: </b> To apply a magnetization transfer-weighted (MTw) imaging to patients with AMN and AMN-like syndrome in order to visualize and quantitatively assess the pathology of white matter tracts in the cervical spinal cord. <b>Methods: </b> MTw studies were conducted in nine men with AMN, eight symptomatic heterozygous women, and 10 age- and sex-matched controls and compared to the Expanded Disability Status Scale (EDSS) and quantitative tests of vibratory sense and postural sway. MTw data sets were obtained at the level of C1 to C3 using a three-dimensional gradient echo acquisition technique, these images were then standardized between subjects by using the in-slice CSF signal as a normalization reference, allowing a quantitative assessment of the MTw signal. <b>Results: </b> In contrast to conventional MRI, MTw images showed signal hyperintensities in the lateral and dorsal columns of all patients. The MT signal quantified in the dorsal column showed significant differences between patients with AMN, X-linked adrenoleukodystrophy heterozygotes, and controls. MT hyperintensity in the dorsal column correlated with EDSS, vibratory sense, and postural sway. <b>Conclusion: </b> Magnetization transfer-weighted imaging is a sensitive modality for the visual and quantitative assessment of spinal cord pathology in adrenomyeloneuropathy, and is a potential tool for evaluation of new therapies.
Differences in Thyroid Cancer
Authors: R. P. Towers
Journal: BMJ (1972)

your article, were treated by radium only, and there seems little doubt that the high uterine dose necessary for a radium meno- pause is more likely to lead to later malig- nancy than the lower dose given by external irradiation.The indications for inducing a radiation menopause are few; for a radium menopause there are none.-I am, etc.,
TCT-315 Invasively Derived Coronary Flow Capacity: Prognostic Implications of a Cross-modality Physiological Concept
Authors: Tim P. van de Hoef, Mauro Echavarria-Pinto, Martijn A. van Lavieren, M. Meuwissen, Patrick W. Serruys, Javier Escaned, Jan Piek
Journal: Journal of the American College of Cardiology (2014)
Treatment of Leukemia by Extracorporeal Irradiation
Authors: E. D. Thomas, R. B. Epstein, J. W. Eschbach, D. Prager, C. D. Buckner, G. Marsaglia
Journal: New England Journal of Medicine (1965)

THE first attempt to irradiate the circulating blood outside the body was made by Heymans1 in 1921. In the following three decades several other investigators undertook studies of extracorporeal irradiation in animals-2 3 4 In the light of current knowledge, extracorporeal irradiation appears to have at least three important objectives. The first is the study of lymphocyte physiology by destruction of these radiosensitive cells in the circulating blood. Utilizing extracorporeal irradiation, Cronkite and his colleagues5 have carried out a series of elegant studies on the lymphocyte physiology of the calf. The second purpose is destruction of immunologically competent cells in the circulating . . .
Attitudes of the public to arthritis.
Authors: E M Badley, P H Wood
Journal: Annals of the Rheumatic Diseases (1979)

A survey of the public's attitude to arthritis was commissioned by the Arthritis and Rheumatism Council (ARC) in 1974. The survey was carried out by National Opinion Polls (NOP) Market Research Ltd. The ARC were interested to find out whether people underestimated arthritis and what they thought about the consequences. Respondents were asked to rank a number of illnesses in terms of their seriousness and the loss of work to which they give rise. They were also shown a series of statements about arthritis and rheumatism in order to elicit the extent of their agreement with the views these represented. The public appear to have fairly realistic ideas about the magnitude of the problem and of its nature and associations. However, although the pain of arthritis and rheumatism was appreciated, their possible impact in terms of disturbance of the normal pattern of daily life tended to be underestimated. The findings reflect the climate of opinion from which present and potential arthritis sufferers come and may therefore reveal part of their attitudes to their disease.
Teaching medical students about disability
Authors: A. Claxton
Journal: BMJ (1994)

If something is to be done about doctors' widespread ignorance of the special needs of disabled people then medical school is the logical place to start. It is there that tomorrow's doctors need to develop positive attitudes to disability and begin to understand the medical and social problems of impairment. At present the attention that medical schools pay to the topic varies widely and is generally inadequate.

Medical Education on Disabilities reviews the current state of play.1 Produced by University College London Medical School and the Prince of Wales's Advisory Group on Disabilities, the report lists …
Reduced Subendocardial Ryanodine Receptors and Consequent Effects on Cardiac Function in Conscious Dogs With Left Ventricular Hypertrophy
Authors: Luc Hittinger, Bijan Ghaleh, Jie Chen, John G. Edwards, Raymond K. Kudej, Mitsunori Iwase, Song-Jung Kim, Stephen F. Vatner, Dorothy E. Vatner
Journal: Circulation Research (1999)

Abstract —The goal of this study was to examine the transmural distribution of ryanodine receptors in left ventricular (LV) hypertrophy (LVH) and its in vivo consequences. Dogs were chronically instrumented with an LV pressure gauge, ultrasonic crystals for measurement of LV internal diameter and wall thickness, and a left circumflex coronary blood flow velocity transducer. Severe LVH was induced by chronic banding of the aorta (12±1 months), which resulted in a 78% increase in LV/body weight. When ryanodine was infused directly into the circumflex coronary artery, it did not affect LV global function or systemic hemodynamics; however, it reduced LV wall thickening and delayed relaxation in the posterior wall in control dogs but was relatively ineffective in dogs with LVH. In LV sarcolemmal preparations, [ 3 H]ryanodine ligand binding revealed a subendocardial/subepicardial gradient in normal dogs. In LVH there was a 45% decrease in ryanodine receptor binding and a loss in the natural subendocardial/subepicardial gradient, which roughly correlated inversely with the extent of LVH and directly with regional wall motion. Both mRNA and Western analyses revealed similar findings, with a reduction of the transmural mRNA levels and a loss in the natural gradient between subendocardial and subepicardial layers in LVH. Thus, ryanodine receptor message and binding in LVH is reduced preferentially in the subendocardium with consequent attenuation of the action of ryanodine in vivo. The selectively altered ryanodine regulation subendocardially in LVH could reconcile some of the controversy in this field and may play a role in mediating decompensation from stable LVH.
Structure and dynamics of the pan-genome of Streptococcus pneumoniae and closely related species
Authors: Claudio Donati, N Luisa Hiller, Hervé Tettelin, Alessandro Muzzi, Nicholas J Croucher, Samuel V Angiuoli, Marco Oggioni, Julie C Dunning Hotopp, Fen Z Hu, David R Riley, Antonello Covacci, Tim J Mitchell, Stephen D Bentley, Morgens Kilian, Garth D Ehrlich, Rino Rappuoli, E Richard Moxon, Vega Masignani
Journal: Genome biology (2010)

Streptococcus pneumoniae is one of the most important causes of microbial diseases in humans. The genomes of 44 diverse strains of S. pneumoniae were analyzed and compared with strains of non-pathogenic streptococci of the Mitis group. Despite evidence of extensive recombination, the S. pneumoniae phylogenetic tree revealed six major lineages. With the exception of serotype 1, the tree correlated poorly with capsular serotype, geographical site of isolation and disease outcome. The distribution of dispensable genes - genes present in more than one strain but not in all strains - was consistent with phylogeny, although horizontal gene transfer events attenuated this correlation in the case of ancient lineages. Homologous recombination, involving short stretches of DNA, was the dominant evolutionary process of the core genome of S. pneumoniae. Genetic exchange occurred both within and across the borders of the species, and S. mitis was the main reservoir of genetic diversity of S. pneumoniae. The pan-genome size of S. pneumoniae increased logarithmically with the number of strains and linearly with the number of polymorphic sites of the sampled genomes, suggesting that acquired genes accumulate proportionately to the age of clones. Most genes associated with pathogenicity were shared by all S. pneumoniae strains, but were also present in S. mitis, S. oralis and S. infantis, indicating that these genes are not sufficient to determine virulence. Genetic exchange with related species sharing the same ecological niche is the main mechanism of evolution of S. pneumoniae. The open pan-genome guarantees the species a quick and economical response to diverse environments.
Adding a Test for Human Papillomavirus DNA to Cervical-Cancer Screening
Authors: Thomas C. Wright, Mark Schiffman
Journal: New England Journal of Medicine (2003)

It is now clear that virtually all squamous-cell cervical carcinomas contain one of 18 types of human papillomavirus (HPV) DNA, as shown definitively in the article by Muñoz et al. in this issue of the Journal (pages 518–527). Although the observation that HPV DNA is routinely detected in cervical cancers is not proof that it has a causal role, the relative risk of cervical cancer associated with high-risk types of HPV is even higher than the risk of lung cancer associated with smoking. Several oncogenes have been identified in high-risk (oncogenic) types of HPV, and the biologic mechanisms of malignant . . .
An antibody to platelet membrane antigen associated with thrombotic events in essential thrombocythemia
Authors: G. Rock, R. K. Smiley, P. Tittley, S. Hashemi, N. McCombie
Journal: American Journal of Hematology (1988)

Abstract A 71‐year‐old man with essential thrombocythemia presented with acute onset of thrombosis in his fingers. The platelet count at presentation was 752 × 10 9 /liter, and his PTT was within the normal range. Platelet aggregation was normal in response to ADP, decreased to epinephrine, and absent to collagen, with the patient receiving 1.2 g aspirin/day. Plasma vWF:Ag was 158 U/dl, VIII: C was 150 U/dl, and the vWF:Ag multirner pattern was normal. HLA antibodies were not detected in his serum, and the platelet‐associated IgG was normal at 3.9 fg/platelet. Incubation of normal, unactivated platelets with the patient's plasma did not result in agglutination of the platelets. However, a serum antibody reacting against a platelet antigen with an apparent molecular weight of 45,000 could be demonstrated by Western blotting. This antibody also reacted with endothelial cells. The reactive pattern was similar to that of commercially obtained actin; the serum antibody could be removed by preincubation with actin. Platelet‐plasmapheresis was carried out daily for 10 days, after which the serum still reacted weakly with the platelet antigen. By day 20, the band could still be identified on the electroblot, but 2 weeks later no band could be seen. Similar assay of sera from six other patients with myeloproliferative disorders and comparable thrombocytosis but without thrombotic manifestations did not show any such reactions. The data suggest a correlation between the presence of an antibody possibly directed against platelet and/or endothelial cell actin and the vascular events in this patient with essential thrombocythemia.
Plastered in pustules
Authors: J. Powell, J. Bhat, S. Orpin
Journal: BMJ (2011)

An 87 year old woman presented with a non-itchy rash that began three weeks ago on the abdomen. Since then it had spread to most of her trunk, face, and lower limbs. She was not systemically unwell.

Her medical history included atrial fibrillation, cerebrovascular disease, hypertension, and an intertriginous reaction for which oral terbinafine 250 mg daily had been started three days before the rash began. Current long term drugs included aspirin, warfarin, alendronic acid, bisoprolol, calcium supplements, candesartan, furosemide, loperamide, and omeprazole. She had no known drug allergies.

On examination, large confluent patches and plaques of oedematous erythema were present especially on the trunk, face, and lower limbs. The palms and soles were spared. Hundreds of small non-follicular based pustules were seen within these areas. No ulceration or blistering was seen.

Blood tests showed normal renal and liver function, C reactive protein (31 mmol/L; normal 0-1.7), total white cell count (15.7 ×109/L; 4.0-11.0), neutrophil count (13.6×109/L; 2.5-7.5), lymphocyte count (1.36×109/L), eosinophil count (0.32×109/L; 0.04-0.44). Haemoglobin and platelet counts were within the normal range.

A swab from a pustule showed no bacterial growth. Histological analysis showed subcorneal pustules.

Terbinafine was stopped immediately and the patient was treated with topical steroids and emollients. The rash began to resolve within a week.



### 1 What is the diagnosis in this case of generalised pustulosis?

#### Short answer

On the basis of the history and clinical and histopathological findings the diagnosis is acute generalised exanthematous pustulosis.

#### Long answer

Acute generalised exanthematous pustulosis is an adverse cutaneous drug eruption in which many small sterile pustules develop within large areas of erythema (figure⇓), often within a few …