tbuckley/cabot-search huggingface dataset:
Late results of the Royal Free Hospital prospective controlled trial of prednisolone therapy in hepatitis B surface antigen negative chronic active hepatitis.
Authors: A P Kirk, S Jain, S Pocock, H C Thomas, S Sherlock
Journal: Gut (1980)

A long-term follow-up of at least 10 years or until death of 44 patients taking part in a controlled prospective trial of prednisolone therapy in hepatitis B antigen negative chronic active hepatitis (lupoid hepatitis) has been performed at the Royal Free Hospital, London. Patients presenting between 1963 and 1967 were randomly allocated into control and treatment groups. Ten year life table survival curves showed a significantly improved survival in the treatment group where 63% of patients were alive at 10 years compared with only 27% in the control group (log rank test, P = 0.03). The median survival in the treatment group was 12.2 years compared with 3.3 years in the control group. The mean duration of treatment was 4.5 years. Age, presence of antinuclear factor, cirrhosis, or level of serum transaminases at presentation did not appear to affect survival. Male patients if untreated had a poorer prognosis than females (P = 0.02). The natural history of chronic active hepatitis appeared from clinical, biochemical, and histological findings to be from an active hepatitis or cirrhosis to inactive macronodular cirrhosis. Prednisolone therapy significantly improved survival by reducing mortality in the early active phase of the disease.
The Strategy of T Cell Antigen-presenting Cell Encounter in Antigen-draining Lymph Nodes Revealed by Imaging of Initial T Cell Activation
Authors: Marc Bajénoff, Samuel Granjeaud, Sylvie Guerder
Journal: The Journal of Experimental Medicine (2003)

The development of an immune response critically relies on the encounter of rare antigen (Ag)-specific T cells with dendritic cells (DCs) presenting the relevant Ag. How two rare cells find each other in the midst of irrelevant other cells in lymph nodes (LNs) is unknown. Here we show that initial T cell activation clusters are generated near high endothelial venules (HEVs) in the outer paracortex of draining LNs by retention of Ag-specific T cells as they exit from HEVs. We further show that tissue-derived DCs preferentially home in the vicinity of HEVs, thus defining the site of cluster generation. At this location DCs efficiently scan all incoming T cells and selectively retain those specific for the major histocompatibility complex–peptide complexes the DCs present. Such strategic positioning of DCs on the entry route of T cells into the paracortex may foster T cell–DC encounter and thus optimize initial T cell activation in vivo.
A murine tumor producing a matrix of basement membrane.
Authors: R W Orkin, P Gehron, E B McGoodwin, G R Martin, T Valentine, R Swarm
Journal: The Journal of Experimental Medicine (1977)

We have studied a murine tumor previously classified as a poorly differentiated chondrosarcoma. Although the cells in this tumor are surrounded by large quantities of extracellular matrix material, the matrix fails to react with stains specific for the sulfated glycosaminoglycans present in normal cartilage. Here we show at the ultrastructural level that the tumor matrix is a homogeneous, nonfibrillar material, resembling basement membrane. Neither the proteoglycan matrix granules nor collagen fibrils characteristic of cartilage are present in the tumor matrix. Amino acid analyses of whole tumor tissue, enzyme-solubilized tumor components, and the protein extracted from lathyritic tumors confirmed that the tumor matrix is a basement membrane collagen. The collagenous protein extracted from the tumor by nonenzymatic means contains three unique polypeptides larger than the alpha-chain components of the other types of collagen. These studies indicate that the tumor is not a type of chondrosarcoma but a basement membrane producing tumor.
Images in Endocrine Pathology: Isolated Langerhans Cell Histiocytosis of the Thyroid in a Patient with Autoimmune Thyroiditis and Hyperthyroidism
Authors: Alexandra Chrisoulidou, Persefoni Xirou, Maria Boudina, Efterpi Margaritidou, Frideriki Patakiouta
Journal: Endocrine Pathology (2015)
Efficacy and Safety Evaluation of Human Reovirus Type 3 in Immunocompetent Animals
Authors: Wen Qing Yang, Xueqing Lun, Cheryl Ann Palmer, M. Elizabeth Wilcox, Huong Muzik, Zhong Qiao Shi, Richard Dyck, Matt Coffey, Brad Thompson, Mark Hamilton, Sandra G. Nishikawa, Penny M. A. Brasher, Kevin Fonseca, David George, N. Berry Rewcastle, Randal N. Johnston, Doug Stewart, Patrick W. K. Lee, Donna L. Senger, Peter A. Forsyth
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Human reovirus type 3 has been proposed to kill cancer cells with an activated Ras signaling pathway. The purpose of this study was to investigate the efficacy of reovirus in immunocompetent glioma animal models and safety/toxicity in immunocompetent animals, including nonhuman primates. Experimental Design: Racine glioma cells 9L and RG2 were implanted s.c. or intracranially in Fisher 344 rats with or without reovirus antibodies, followed by treatment of reovirus. To study whether reovirus kills contralateral tumors in the brain and to determine viral distribution, we established an in situ dual tumor model followed by reovirus intratumoral inoculation only into the ipsilateral tumor. To evaluate neurotoxicity/safety of reovirus, Cynomolgus monkeys and immunocompetent rats were given intracranially with reovirus, and pathological examination and/or behavioral studies were done. Viral shedding and clinical biochemistry were systematically studied in monkeys. Results: Intratumorally given reovirus significantly suppressed the growth of both s.c. and intracranially tumors and significantly prolonged survival. The presence of reovirus-neutralizing antibodies did not abort the reovirus’ antitumor effect. Reovirus inhibited glioma growth intracranially in the ipsilateral but not the contralateral tumors; viral load in ipsilateral tumors was 15 to 330-fold higher than the contralateral tumors. No encephalitis or behavioral abnormalities were found in monkeys and rats given reovirus intracranially. No treatment-related clinical biochemistry changes or diffuse histopathological abnormality were found in monkeys inoculated intracranially with Good Manufacturing Practice prepared reovirus. Microscopic changes were confined to the region of viral inoculation and were dose related, suggesting reovirus intracranially was well tolerated in nonhuman primates. Conclusions: These data show the efficacy and safety of reovirus when it is used in the treatment of gliomas in immunocompetent hosts. Inoculation of reovirus into the brain of nonhuman primates did not produce significant toxicities.
The doctor's PDA and Smartphone handbook
Authors: P. Carter
Journal: Journal of the Royal Society of Medicine (2006)

Whilst reading the article by Drs Paton and Al-Ubaydli (February 2006 JRSM1) on the task list, I was reminded of an earlier piece of invaluable technology that I used when I was a house officer. The technology, known as a piece of paper, allowed, with the use of an additional item known as a pen, me to keep notes and task lists on all my patients as I dutifully trotted behind my consultant. If large enough, it also provided a convenient place to stick those handy patient information labels—freeing up my sleeve for wiping my nose. Purging was simply a matter of crossing off tasks as they were completed and shredding the paper at the end of the day.

I do hope that Drs Patton and Al-Ubaydli will forgive my slightly facetious response when I admit to occasionally using the `reminder' function on my mobile phone to assist my own personal organizational skills.
The Physician's Estate
Authors: None Bruce
Journal: JAMA (1977)

A THREE-PART series entitled "The Physician's Estate" has recently been concluded inThe Journal(236:1743, 2217, and 2796, 1976). As was indicated, this series of articles was prepared long before the recent 1976 statutory changes in the federal estate and gift tax law. The information in this series of articles did not, therefore, reflect these changes in the law. It would be impossible to detail all of the changes that were enacted in the limited time and space available. Changes in the major federal tax provisions that were discussed before, though, can be noted. This will include mention of the new federal estate and gift tax rates and structure, current filing requirements, marital deduction limits, and gifts in contemplation of death. <h3>Unified Estate and Gift Tax Rates</h3> The basic federal estate and gift tax structure had been the same for many years. The 1976 tax law changes have introduced a
Whole Chromosome Alterations Predict Survival in High-Risk Neuroblastoma without <i>MYCN</i> Amplification
Authors: Sven Bilke, Qing-Rong Chen, Jun S. Wei, Javed Khan
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Patients with stage IV neuroblastoma over the age of 500 days without MYCN amplification have a survival rate of &amp;lt;30% and there are currently no reliable means of predicting which of these patients will survive or succumb to the disease. The goal of this study is to develop a DNA copy number–based prognostic profile for these patients. Experimental Design: We have used comparative genomic hybridization to identify genome copy number changes that can predict outcome in patients with stage IV neuroblastoma without MYCN amplification. Results: A strong correlation of patient survival with the presence of whole chromosome changes (WCC ≥2) was observed, even in the group of patients older than 500 days at time of diagnosis. This novel prognostic marker showed a significant dependence on the date of diagnosis; patients with WCC ≥2 diagnosed after 1998 had a significantly higher probability of survival compared with those diagnosed earlier. At the same time, no such time dependence was found among the samples with WCC &amp;lt;2, suggesting that medical progress patients in recent years has particularly benefited those patients with a stage IV non–MYCN-amplified disease if WCC ≥2 were present. Conclusions: In this pilot study, we present a novel prognostic marker for survival of high-risk neuroblastoma patients over the age of 500 days without MYCN amplification and diagnosed after 1998. Further validation study is required to establish this risk stratification for these patients.
Deep Conservation of Human Protein Tandem Repeats within the Eukaryotes
Authors: Elke Schaper, Olivier Gascuel, Maria Anisimova
Journal: Molecular Biology and Evolution (2014)

Tandem repeats (TRs) are a major element of protein sequences in all domains of life. They are particularly abundant in mammals, where by conservative estimates one in three proteins contain a TR. High generation-scale duplication and deletion rates were reported for nucleic TR units. However, it is not known whether protein TR units can also be frequently lost or gained providing a source of variation for rapid adaptation of protein function, or alternatively, tend to have conserved TR unit configurations over long evolutionary times. To obtain a systematic picture, we performed a proteome-wide analysis of the mode of evolution for human protein TRs. For this purpose, we propose a novel method for the detection of orthologous TRs based on circular profile hidden Markov models. For all detected TRs, we reconstructed bispecies TR unit phylogenies across 61 eukaryotes ranging from human to yeast. Moreover, we performed additional analyses to correlate functional and structural annotations of human TRs with their mode of evolution. Surprisingly, we find that the vast majority of human TRs are ancient, with TR unit number and order preserved intact since distant speciation events. For example, ≥61% of all human TRs have been strongly conserved at least since the root of all mammals, approximately 300 Ma. Further, we find no human protein TR that shows evidence for strong recent duplications and deletions. The results are in contrast to the high generation-scale mutability of nucleic TRs. Presumably, most protein TRs fold into stable and conserved structures that are indispensable for the function of the TR-containing protein. All of our data and results are available for download from http://www.atgc-montpellier.fr/TRE.
Prognostic Effect of Insertion/Deletion Polymorphism of the ACE Gene on Renal and Cardiovascular Clinical Outcomes in Chinese Patients With Type 2 Diabetes
Authors: Ying Wang, Maggie C.Y. Ng, Wing Yee So, Peter C.Y. Tong, Ronald C.W. Ma, Chun Chung Chow, Clive S. Cockram, Juliana C.N. Chan
Journal: Diabetes Care (2005)

OBJECTIVE— The insertion/deletion (I/D) polymorphism of the ACE gene has been reported to be associated with diabetic microvascular or macrovascular complications. The aim of the present study was to investigate the prognostic effect of I/D polymorphism on renal and cardiovascular clinical outcomes in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS— A consecutive cohort of 1,281 Chinese patients with type 2 diabetes were followed for 41.3 ± 21.6 months. Renal end points were defined as renal death and events (need for dialysis, plasma creatinine ≥500 μmol/l, or doubling of plasma creatinine of baseline value ≥150 μmol/l). Cardiovascular end points were defined as cardiovascular death and events, which included ischemic heart disease, heart failure, cerebrovascular accident, and revascularization requiring hospital admission. The I/D polymorphism of the ACE gene was examined by PCR followed by agarose gel electrophoresis. RESULTS— The frequencies of ACE gene I/D polymorphisms were in Hardy-Weinberg equilibrium. Patients who developed a renal end point (n = 98) had higher frequencies of DD genotype (19.4 vs. 10.8%, P = 0.018) and D allele (41.3 vs. 31.8%, P = 0.006) compared with subjects who did not (n = 1,183). The cumulative rates of renal end points were 10.0, 19.2, and 24.4% in the II (n = 595), DI (n = 539), and DD genotype carriers (n = 147), respectively (log rank P = 0.004). In multiple Cox regression analysis, the occurrence of renal end points remained significantly influenced by I/D polymorphism with a dominant deleterious effect of the DD genotype (DD versus II, adjusted hazard ratio 2.80 [95% CI 1.49–5.29]). There was no prognostic effect of I/D polymorphism on cardiovascular end points. CONCLUSIONS— The DD genotype of the ACE I/D polymorphism was an independent risk factor for renal but not cardiovascular end points in Chinese patients with type 2 diabetes.
A Step Backward—or Is it Forward?
Authors: Saul Genuth, Richard Kahn
Journal: Diabetes Care (2008)

The time may have come—or at least will soon arrive—when the diagnostic categories related to diabetes and its close relatives, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), should be reconsidered. IGT, IFG, and the combination of the two are now considered pre-diabetes because, compared with normal glucose tolerance, they signal an increased risk of developing diabetes (1). Before 1979, when the National Diabetes Data Group defined IGT (2) and declared it to be an official diagnostic category, one either did or did not have diabetes and nondiagnostic glucose levels were de facto “normal.” A middle ground was recognized by some physicians, but it was not enshrined in all epidemiological studies or in clinical practice.

The addition of IFG in 1997 for the purpose of creating a state equivalent to IGT both added to the middle ground and raised awareness and appreciation of intermediate levels of glucose intolerance (3). There was now a distinctive group of individuals whose fasting plasma glucose (FPG) lay between normal (<110 mg/dl) and the new 1997 lower diabetes cut point of 126 mg/dl and who may not meet the IGT criterion of 140–199 mg/dl 2 h after a standard oral glucose load of 75 g (3). A further refinement of IFG in 2003 altered the lower IFG cut point from 110 to 100 mg/dl, a change recommended to make both intermediate states equivalent and to define a more realistic upper limit of normal (4).

Recently, however, more and more studies have demonstrated that at glycemic levels above normal but within the range of either IFG or IGT, there is an increasing risk of crossing the diabetes line (FPG 126 mg/dl and/or a 2-h post–glucose load level of 200 mg/dl) within a few years (1). These latter numbers are based on the association of …
Evaluation of hepatocellular function by way of receptor-mediated uptake of a technetium-99m—labeled asialoglycoprotein analog
Authors: Neville R. Pimstone, Robert C. Stadalnik, David R. Vera, Dusan P. Hutak, Walter L. Trudeau
Journal: Hepatology (1994)

We have developed a quantitative functional imaging study of the liver using a radiolabeled asialoglycoprotein analog, Tc–galactosyl–neoglycoalbumin. Heart and liver time–activity data can be transformed by automated kinetic analysis into asialoglycoprotein hepatocyte receptor concentration. Twenty–eight healthy controls, 46 patients with noncholestatic chronic liver injury and 11 patients with primary biliary cirrhosis were studied. Liver function was also assessed by Pugh modified–Child–Turcotte criteria, 14C–aminopyrine breath test and indocyanine green clearance (24 patients). Results: (a) In normal controls with a Child–Turcotte criteria score of 5, receptor concentration ranged from 0.63 to 1.19 μmol/L, with a mean 0.83 ± 2 S.D. 0.06 μmol/L, which was significantly higher (p &lt; 0.001) than that of the patient group (mean receptor concentration = 0.44 ± 2 S.D. 0.04 μmol/L). In cirrhotic patients with Child–Turcotte criteria score of 5, the mean receptor concentration was 0.60 ± 2 S.D. 0.07 μmol/L, which was significantly lower than controls (p &lt; 0.01). In end–stage cirrhosis (Child–Turcotte criteria score 11 to 15), a group in which patients died or required orthotopic liver transplantation within 1 yr, the mean receptor concentration was 0.35 ± 2 S.D. to 0.07 μmol/L. The sensitivity and specificity for receptor concentration in relation to liver disease, with values above 0.65 μmol/L being normal, were 0.96 and 0.88, respectively. Receptor concentration correlated well with Child–Turcotte criteria score (r = 0.78, p = &lt;0.001), with aminopyrine breath test (r = 0.75, p = &lt;0.001) and with indocyanine green clearance (r = 0.88, p = &lt;0.001). (b) Among 11 primary biliary cirrhosis patients, ten had Child–Turcotte criteria score of 5. Receptor concentration and aminopyrine breath test values were lower in primary biliary cirrhosis patients with liver biopsy histological stage III–IV than I–II, although the numbers were too small for statistical analysis. We conclude that determination of receptor concentration, a rapid and bilirubin–independent method of quantitating hepatocellular function, correlates well with Child–Turcotte criteria score, aminopyrine breath test and indocyanine green clearance. This could prove valuable in evaluating the extent and the progression of liver disease and the impact of newer therapies in retarding chronic cholestatic and viral liver injury. Long–term studies are needed to confirm this speculation. (Hepatology 1994;20:917-923).
Food debris in trachestomic tube
Authors: M. Marchese, G. Cusumano, C. Spada, P. Granone, G. Costamagna
Journal: Gut (2010)

A 59-year-old man with previous total laryngectomy for squamous cell carcinoma was referred to our department for fever, cough and recurrent pneumonia lasting for the past 5 months. The patient did not receive adjuvant radiochemotherapy and never showed neoplastic recurrence during follow-up. After 3 years, he developed myocardial infarction, he was re-hospitalised in an intensive care unit, and he was treated by mechanical ventilation after tracheostomy tube placement. Three months after discharge, the patient developed progressive dysphagia, coughing and gradual clinical deterioration. He …
Mobilization of pro-inflammatory lipids in obese Plscr3-deficient mice
Authors: David M Mutch, Grace O'Maille, William R Wikoff, Therese Wiedmer, Peter J Sims, Gary Siuzdak
Journal: Genome biology (2007)

The obesity epidemic has prompted the search for candidate genes capable of influencing adipose function. One such candidate, that encoding phospholipid scramblase 3 (PLSCR3), was recently identified, as genetic deletion of it led to lipid accumulation in abdominal fat pads and changes characteristic of metabolic syndrome. Because adipose tissue is increasingly recognized as an endocrine organ, capable of releasing small molecules that modulate disparate physiological processes, we examined the plasma from wild-type, Plscr1-/-, Plscr3-/- and Plscr1&3-/- mice. Using an untargeted comprehensive metabolite profiling approach coupled with targeted gene expression analyses, the perturbed biochemistry and functional redundancy of PLSCR proteins was assessed.Nineteen metabolites were differentially and similarly regulated in both Plscr3-/- and Plscr1&3-/- animals, of which five were characterized from accurate mass, tandem mass spectrometry data and their correlation to the Metlin database as lysophosphatidylcholine (LPC) species enriched with C16:1, C18:1, C20:3, C20:5 and C22:5 fatty acids. No significant changes in the plasma metabolome were detected upon elimination of PLSCR1, indicating that increases in pro-inflammatory lipids are specifically associated with the obese state of Plscr3-deficient animals. Correspondingly, increases in white adipose lipogenic gene expression confirm a role for PLSCR3 in adipose lipid metabolism.The untargeted profiling of circulating metabolites suggests no detectable functional redundancies between PLSCR proteins; however, this approach simultaneously identified previously unrecognized lipid metabolites that suggest a novel molecular link between obesity, inflammation and the downstream consequences associated with PLSCR3-deficiency.
Degradable Hyaluronic Acid/Protamine Sulfate Interpolyelectrolyte Complexes as miRNA‐Delivery Nanocapsules for Triple‐Negative Breast Cancer Therapy
Authors: Shihua Wang, Minjun Cao, Xiongwei Deng, Xiangqian Xiao, Zhaoxia Yin, Qin Hu, Zhixiang Zhou, Fang Zhang, Ruirui Zhang, Yan Wu, Wang Sheng, Yi Zeng
Journal: Advanced Healthcare Materials (2014)

Metastatic relapse is a leading cause of cancer‐associated death and one of the major obstacles for effective therapy against triple‐negative breast cancer. To address this problem, a miRNA‐delivering nanocapsule technology based on hyaluronic acid (HA)/protamine sulfate (PS) interpolyelectrolyte complexes (HP‐IPECs) is developed for efficient encapsulation and intracellular delivery microRNA‐34a (miR‐34a), which is a potent endogenous tumor suppressor of breast cancer. The nanocapsules are successfully generated through a self‐assembly approach mediated by an electrostatic interaction. In vitro and in vivo experiments illustrate that miR‐34a can be efficiently encapsulated into HP‐IPECs and delivered into breast cancer cells or breast cancer tissues. Nanocomplex‐assisted delivery of miR‐34a induces cell apoptosis and suppresses migration, proliferation, and tumor growth of breast cancer cells via targeting CD44 and a Notch‐1‐signaling pathway. The obtained results suggest that HP‐IPECs have a great potential as a biodegradable vector for microRNA‐based therapy against triple‐negative breast cancer.