tbuckley/cabot-search huggingface dataset:
Biological therapies improve inflammatory bowel disease symptoms, national audit finds
Authors: M. Gould
Journal: BMJ (2013)

Adults and children with inflammatory bowel disease are reporting decreases in the severity of their condition and fewer are having surgery after being treated with monoclonal antibody therapies.

Data from the first national report of biological therapies show that 62% of adult patients and 73% of paediatric patients saw the severity of their disease decrease after 12 weeks of treatment with two drugs—infliximab, a chimeric anti-TNFα monoclonal antibody, and adalimumab, a recombinant human immunoglobulin (IgG1) monoclonal antibody—known collectively as biological therapies.1

Inflammatory bowel disease affects approximately 240 000 people in the United Kingdom and patients with ulcerative colitis and Crohn’s disease will often require surgery during their lifetime. Biological therapies have been available since the 1990s and are used extensively in treating rheumatological disease and have also been used to treat patients with severe Crohn’s disease.

The …
Intrauterine Pulmonary Hypertension Impairs Angiogenesis <i>In Vitro</i>
Authors: Jason Gien, Gregory J. Seedorf, Vivek Balasubramaniam, Neil Markham, Steven H. Abman
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Mechanisms that impair angiogenesis in neonatal persistent pulmonary hypertension (PPHN) are poorly understood.Objectives: To determine if PPHN alters fetal pulmonary artery endothelial cell (PAEC) phenotype and impairs growth and angiogenesis in vitro, and if altered vascular endothelial growth factor–nitric oxide (VEGF–NO) signaling contributes to this abnormal phenotype.Methods: Proximal PAECs were harvested from fetal sheep that had undergone partial ligation of the ductus arteriosus in utero (PPHN) and age-matched control animals. Growth and tube formation ± VEGF and NO stimulation and inhibition were studied in normal and PPHN PAECs. Western blot analysis was performed for VEGF, VEGF receptor-2 (VEGF-R2), and endothelial NO synthase (eNOS) protein content. NO production with VEGF administration was measured in normal and PPHN PAECs.Measurements and Main Results: PPHN PAECs demonstrate decreased growth and tube formation in vitro. VEGF and eNOS protein expression were decreased in PPHN PAECs, whereas VEGF-R2 protein expression was not different. VEGF and NO increased PPHN PAEC growth and tube formation to values achieved in normal PAECs. VEGF inhibition decreased growth and tube formation in normal and PPHN PAECs. NOS inhibition decreased growth in normal and PPHN PAECs, but tube formation was only reduced in normal PAECs. NO reversed the inhibitory effects of VEGF-R2 inhibition on tube formation in normal and PPHN PAECs. VEGF increased NO production in normal and PPHN PAECs.Conclusions: PPHN in utero causes sustained impairment of PAEC phenotype in vitro, with reduced PAEC growth and tube formation and down-regulation of VEGF and eNOS protein. VEGF and NO enhanced growth and tube formation of PPHN PAECs.
Abstract 5055: TOPK phosphorylation of Prx1 at Ser32 prevents UVB-induced apoptosis in RPMI7951 melanoma cells through regulation of its peroxidase activity and blockade of intracellular accumulation of H2O2
Authors: Tatyana Zykova, Feng Zhu, Tatyana I. Vakorina, Jishuai Zhang, LeeAnn Higgins, Dasha V. Urusova, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2010)

Abstract A novel serine/threonine kinase, T-LAK cell-originated protein kinase (TOPK), is only expressed in a wide range of cancer cells. We previously showed that TOPK increases colorectal cancer growth in vivo and ex vivo and that melanoma cell lines with a high abundance of TOPK protein exhibit a marked resistance to As3+-induced apoptosis. Here we continue our investigation of the functional details of TOPK. LC/MS/MS data showed that TOPK can bind with peroxiredoxin 1 (Prx1), which regulates hydrogen peroxide-mediated signal transduction. The role of Prx1 phosphorylation induced by UV in melanoma is not clear. Here, we provide evidence that TOPK phosphorylates Prx1 at Ser32 in vitro. Analysis of the CD spectra of Prx1 and a mutant Prx1 (S32A) protein shows that the secondary structure of Prx1 was significantly altered by its phosphorylation at Ser32. UVB radiation induced phosphorylation of TOPK in a time-dependent manner in RPMI7951 human melanoma cells and phosphorylated TOPK co-localized with Prx1 in the nucleus. UVB treatment increased peroxidase activity of Prx1 in vitro and ex vivo. The level of H2O2 was increased in TOPK siRNA cells and in RPMI7951 cells stably overexpressing mutant Prx1 (S32A). In addition, apoptosis was dramatically increased in TOPK siRNA cells and decreased in WT-Prx1 stable cells after UVB treatment. Our results suggested that TOPK phosphorylation of Prx1 at Ser 32 prevents UVB-induced apoptosis in RPMI7951 melanoma cells through the regulation of Prx1 peroxidase activity by blocking intracellular accumulation of H2O2. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5055.
SURGICAL CONSERVATISM OF THE OVARIES AND FALLOPIAN TUBES.
Authors: EDWIN RICKETTS
Journal: JAMA (1902)

Pathologic lesions of one or both ovaries and Fallopian tubes may be so serious as to call for the most radical surgical measures, even extirpation. There are cases in which extirpation is practiced unnecessarily by operators of limited experience and the conservation of these organs has not received the attention it deserves. It is of this incompetent work, which brings poor results and a high mortality, that I wish to speak. There can be no reasonable excuse offered, nor apology made, for the poor results obtained from the lack of true and intelligent conservatism. Many competent men have explicitly expressed themselves in this regard, but not through channels where their statements would do the most good. Just criticisms have emanated from many of the best men in general practice. Hydrosalpinx was once recognized as a condition which demanded that the Fallopian tube be removed, together with the ovaries, whether diseased
Districts' use of thrombolytic agents
Authors: S G Fort, A G Chappell
Journal: BMJ (1990)

of the small intestine.'In vivo the result of addition of fibre was a less pronounced glucose and insulin response'-effects that could be reproduced by using starchy foods, which for various reasons including particle size" were digested slowly in vitro.Thus slow absorption provided a rationale for including dietary fibre and carbohydrate foods of lowr glvcaemic index in general in the diet of diabetic patients.Through the reduction of insulin secretion slow absorption provided an additional reason why these manoeuvres max lower serum lipid concentrations.For us, nibbling was a further test of the effects of slow absorption which, without changing the nature of the food, might produce benefits similar to those of fibre on carbohydrate and lipid metabolism.We therefore wish to acknowledge a consider- able debt to Professor Sotithgate for his extension of the fibre hypothesis.His proposal provided the basis for a mechanism of action of several potentially useful approachcs to the treatment of disease, including the use of fibre and gastrointestinal enzyme inhibition.It has contributed to the delay- ing of absorption now being called a therapeutic principle.
New coroner's system will require two people to verify cause of death
Authors: Clare Dyer
Journal: BMJ (2004)

The biggest overhaul of the coroner's system in England and Wales for 200 years was announced by the government last week, as well as new, more rigorous procedures for certifying deaths.

The new, two stage death certificate process is designed to close the loopholes that allowed the GP Harold Shipman to conceal his murder of more than 200 patients. Reforms to the coroner system will result in a change in the number of coroners from 127 full and part timers to between …
30. AdenoLibrary for Construction and Selection of Targeted Adenoviruses
Authors: Sam C. Noureddini, Alexander Krendelshchikov, Vera Simonenko, Joanne T. Douglas, David T. Curiel, Nikolay Korokhov
Journal: Molecular Therapy (2005)

Top of pageAbstract
Vector systems derived from the human adenovirus serotype 5 (Ad5) have shown promise as gene delivery vehicles for a variety of clinical applications. However, the paucity of the Ad5 primary receptor (coxsackie and adenovirus receptor, CAR) on target cells of interest has rendered many tissues refractory to Ad-mediated transduction. Additionally, this endogenous tropism may potentially lead to undesired transduction of tissues expressing CAR. In view of this, strategies have been proposed to modify Ad5 to achieve targeted gene delivery, by ablating native tropism while redirecting Ad to target cell markers of interest. Such strategies involve modification of the trimeric capsid fiber ligands tend to lose specificity and/or affect virion integrity. As an alternative, several so-called knob-less fiber platforms have been utilized. These protein, whose C-terminal knob domain has been shown to dictate the native tropism associated with Ad5. While approaches employing genetic fusion of simple targeting ligands to the fiber have shown promise in retargeting, in many cases, the incorporated modifications are based on the concept of replacing the native fiber with an alternative protein capable of providing the trimerization functions that the knob usually confers. Such a strategy would accrue the additional benefit of an expanded repertoire of incorporable ligands, based on removal of the structural constraints imposed by the fiber knob. Previously, our group has utilized the bacteriophage T4 fibritin protein for fiber replacement, with subsequent display of complex targeting ligands providing for expanded tropism. However, vectors employing these knob-less fiber platforms often exhibit poor capsid incorporation of the alternate fibers in comparison to that of wild-type Ad5 fiber, which consequently leads to limited gene transfer efficacy and difficulty in vector propagation. In view of these obstacles, we have hypothesized that direct analysis of modified adenoviruses during their rescue/propagation is the only straightforward approach that guarantees the selection of functional, targeted vectors with optimized structural integrity and targeting efficiency. Herein, we describe a new schema for Ad vector construction, which allows for the selection of vectors with the optimal modified capsid configuration at the level of viral rescue. Based on our first generation fiber-fibritin molecule, several new fibers employing variant amounts of fibritin and Ad5 fiber shaft were analyzed via this library selection schema. Our selected variant, composed of the entire Ad5 fiber shaft connected to 12th coiled-coil segment of fibritin, is capable of efficient fiber incorporation, ligand display, and CAR-independent transduction. Furthermore, we have concluded that various targeting ligands require individual optimization, which may be accomplished by utilizing this adenoviral library approach.
The Rinso eaters of Groote Eylandt.
Authors: D S Watson
Journal: BMJ (1983)

Salmonella gastroenteritis associated with erythema nodosumThere are several well established causes of erythema nodosum, and two case reports of erythema nodosum occurring after salmonella gastroenteritis have suggested that this infection may be an additional cause. 1 2Both cases seem to have been isolated ones; admission to hospital was necessary in both.In October 1981 an outbreak of Salmonella typhimurium gastro- enteritis occurred in our practice, which affected over 700 patients and was bacteriologically proved in 440.During this outbreak three cases of erythema nodosum were seen. Case reportsCase 1-A 10 year old previously well girl developed diarrhoea.Stool culture was positive for S typhimurium.She was not unduly ill and recovered quickly, but 14 days later she developed typical erythema nodosum on her well.
869 The bile acid taurocholic acid protects against TNF-alpha induced cholangiocyte apoptosis in bile duct ligated (BDL) rats by activation of the PI3K/AKT-dependent pathway
Authors: S TAFFETANI, S GLASER, H FRANCIS, Y UENO, T PATEL, J PHINIZY, M MARZIONI, A BENEDETTI, G FAVA, B BAUMANN
Journal: Hepatology (2003)
Reflections on the Problems of Surgical Infections
Authors: Champ Lyons
Journal: JAMA (1960)

AS AN AFTERMATH of the rapid progress in antibiotic therapy and as a prelude to the new problems in infection inherent in human contact with other planets, this symposium and panel were arranged. It seems fitting that the time usually allotted for the Chairman's Address should be used for a brief survey of areas of current interest in order that the remarks of our distinguished speakers may have increased pertinency. The prevention of tetanus by active immunization with toxoid stands out as the most brilliant achievement in clinical microbiology. The induced immunity is durable and predictable, with the rare exception of the individual whose total capacity to produce antibodies is suppressed by disorder of globulin synthesis. Primary active immunity is obtained by giving three doses of the alum-precipitated toxoid subcutaneously. The second dose is given 1 month after the first; the third dose, 6 to 12 months later. Booster doses
IMMUNOLOGIC STUDIES OF AUTOIMMUNE DISEASE IN NZB/NZW F1 MICE
Authors: B. C. Seegal, L. Accinni, G. A. Andres, S. M. Beiser, C. L. Christian, B. F. Erlanger, K. C. Hsu
Journal: The Journal of Experimental Medicine (1969)

For the past 3 years NZB and NZW mice have been maintained by sister-brother matings from English breeder stock. NZB/NZW F(1) hybrids developed lupus-like nephritis during the 6th to 7th month and few survived beyond the 8th month. Renal tissues of these animals were examined with fluorescein-labeled antinucleoside sera, specific for thymine and cytosine, for the presence of denatured DNA in GCW, and with labeled antibody to mouse IgG for the presence of excess host globulin in the same areas. The following results have been obtained: (a) All 51 hybrids, over 5 months of age, had an excess of mouse globulin in GCW. 40 animals between the ages of 5 and 12 months showed, in the same areas, antigens which bound one or both of the antinucleoside antibodies. (b) Renal tissues of 19 NZB mice, 5-19 months old, and 27 NZW mice, 2-18 months old, were examined. Excess host globulin was seen in GCW of 13 NZB and 20 NZW animals. The tissues of only two old NZB mice, 14 months of age, bound antinucleoside antibody but none of the other animals did. The association of rapidly fatal lupus-like nephritis in NZB/NZW F(1) mice with denatured DNA and mouse globulin in GCW supports the hypothesis involving this antigen-antibody complex in the pathogenesis of the disease.
Detection of edema associated with myocardial ischemia by computerized tomography in isolated, arrested canine hearts.
Authors: W J Powell, J wittenberg, R A Maturi, R E Dinsmore, S W Miller
Journal: Circulation (1977)

This study was undertaken to determine if computerized tomography (CT scanning) with an EMI cranial scanner could detect edema associated with myocardial ischemia in canine hearts. A localized area of decreased density in the posterior papillary muscle and surrounding myocardium was detected on serial 8 mm CT scan slices of each heart after 60 min of circumflex artery occlusion and 45 min of reflow of blood. The wet/dry weight ratios and previous electron microscope studies of the ischemic posterior papillary muscles revealed edema accumulation. After 1 hour of arterial occlusion and 12 hours of reflow (which produces extensive necrosis and a decrease in the wet/dry ratio) lesions were still discernible but were less consistently as severe. Permanent ligation of the left anterior descending coronary artery and major collateral arteries for 6 hours also resulted in a lesion of decreased density in the distribution of the occluded arteries. Thus, CT scanning can detect, and is a potential means for sequential noninvasive quantitation of myocardial edema associated with ischemia.
Review of Electromagnetic Techniques for Breast Cancer Detection
Authors: Ahmed M. Hassan, Magda El-Shenawee
Journal: IEEE Reviews in Biomedical Engineering (2011)

Breast cancer is anticipated to be responsible for almost 40,000 deaths in the USA in 2011. The current clinical detection techniques suffer from limitations which motivated researchers to investigate alternative modalities for the early detection of breast cancer. This paper focuses on reviewing the main electromagnetic techniques for breast cancer detection. More specifically, this work reviews the cutting edge research in microwave imaging, electrical impedance tomography, diffuse optical tomography, microwave radiometry, biomagnetic detection, biopotential detection, and magnetic resonance imaging (MRI). The goal of this paper is to provide biomedical researchers with an in-depth review that includes all main electromagnetic techniques in the literature and the latest progress in each of these techniques.
Reappraising Florence Nightingale
Authors: K. Williams
Journal: BMJ (2008)

Aging is the greatest risk factor for the development of neurodegenerative diseases, yet we still do not understand how the aging process leads to pathological vulnerability. The research community has relied heavily on mouse models, but the considerable anatomical, physiological, and cognitive differences between mice and humans limit their translational relevance. Ultimately, these barriers necessitate the development of novel aging models. As a non-human primate, the common marmoset (<i>Callithrix jacchus</i>) shares many features in common with humans and yet has a significantly shorter lifespan (10 years) than other primates, making it ideally suited to longitudinal studies of aging. Our objective was to evaluate the marmoset as a model of age-related cognitive impairment. To do this, we utilized the Delayed Recognition Span Task (DRST) to characterize age-related changes in working memory capacity in a cohort of sixteen marmosets, of both sexes, varying in age from young adult to geriatric. These monkeys performed thousands of trials over periods of time ranging up to 50 percent of their adult lifespan. To our knowledge, this represents the most thorough cognitive profiling of any marmoset aging study conducted to-date. By analyzing individual learning curves, we found that aged animals exhibited delayed onset of learning, slowed learning rate after onset, and decreased asymptotic working memory performance. These findings are not accounted for by age-related impairments in motor speed and motivation. This work firmly establishes the marmoset as a model of age-related cognitive impairment. <b>Significance Statement:</b> Understanding the normal aging process is fundamental to identifying therapeutics for neurodegenerative diseases for which aging is the biggest risk factor. Historically, the aging field has relied on animal models that differ markedly from humans, constraining translatability. Here, we firmly establish a short-lived non-human primate, the common marmoset, as a key model of age-related cognitive impairment. We demonstrate, through continuous testing over a substantial portion of the adult marmoset lifespan, that aging is associated with both impaired learning and working memory capacity, unaccounted for by age-related changes in motor speed and motivation. Characterizing individual cognitive aging trajectories reveals inherent heterogeneity, which could lead to earlier identification of the onset of impairment, and extended timelines during which therapeutics are effective.
S100A8-S100A9 Protein Complex Mediates Psoriasis by Regulating the Expression of Complement Factor C3
Authors: Helia B. Schonthaler, Juan Guinea-Viniegra, Stefanie K. Wculek, Isabel Ruppen, Pilar Ximénez-Embún, Ana Guío-Carrión, Raquel Navarro, Nancy Hogg, Keith Ashman, Erwin F. Wagner
Journal: Immunity (2013)
A QUANTITATIVE STUDY OF THE PRECIPITIN REACTION BETWEEN TYPE III PNEUMOCOCCUS POLYSACCHARIDE AND PURIFIED HOMOLOGOUS ANTIBODY
Authors: Michael Heidelberger, Forrest E. Kendall
Journal: The Journal of Experimental Medicine (1929)

1. A quantitative study of the reaction between the soluble specific substance of Type III pneumococcus and its homologous antibody has been made. 2. The entire reaction, from excess of antibody, to excess of specific substance with its accompanying inhibition zone effect, may be expressed by three mass-law equations. 3. The significance of these findings is discussed.
Laryngismus Stridulus: Its Pathology and Treatment
Authors: T. Paget
Journal: BMJ (1857)

pregnancy.She was tapped as for ovarian dropsy; unhappily it was an hepatic cyst, not united to the abdominal parietes, some of the fluid escaped into peritoneum, succeeded by death in eighteeen houirs.Insufficient stress hadl been laid upon the sufferer's statemeut that the swelling-commiienced at epigas- trium.It is probable.that if the nature of the tumour had appeared doubtful, anid the openingi into cyst had been cautiously effected throughl the intervention of potassa fusa, the patient's life wouild have been spare(l.This unfortunate instance may be serviceable as a warning and as a hlint in Dr. Markhams interesting case.
Prevalence of diabetes estimated by plasma glucose criteria combined with standardized measurement of HbA1c among health checkup participants on Miyako Island, Japan.
Authors: Y Takahashi, M Noda, S Tsugane, T Kuzuya, C Ito, T Kadowaki
Journal: Diabetes Care (2000)

To estimate the prevalence of diabetes in participants of an annual health checkup in the district of the Miyako Public Health Center (Okinawa, Japan) by using the revised criteria of the Japan Diabetes Society (JDS).The subjects studied here were all Japanese and 45-75 years of age at the time of the health examination in 1998. Diagnosis of diabetes was based on the following: 1) fasting plasma glucose > or =7.0 mmol/l, 2) casual plasma glucose > or =11.1 mmol/l, 3) HbA(1c) > or =6.1%, and 4) self-report on a special questionnaire given at the examination. The HbA(1c) value was standardized by the measurement of 2 standard samples provided by the JDS.Among the 2,621 subjects, 59.7% had their fasting blood glucose levels measured. Of the subjects diagnosed as having diabetes, 154 (12.6%) were men and 115 (8.6%) women. Among the subjects newly diagnosed with diabetes from their fasting blood glucose levels. 27.5% of the men and 21.9% of the women had diagnoses based on HbA(1c) alone. Overall, 34.9% of the subjects with newly diagnosed diabetes were identified by plasma glucose (PG) alone and 33.0% were diagnosed by HbA(1c) alone.The combination of PG and HbA(1c) resulted in a considerable increase in newly diagnosed diabetes as compared with the use of only one of these parameters. Considering the convenience and correlation with vascular complications, use of the 2 tests may be beneficial in epidemiological studies of the Japanese population to identify high-risk groups for micro- and macrovascular diseases.
Government drops plans for generic substitution amid safety concerns
Authors: Z. Kmietowicz
Journal: BMJ (2010)

The government has said it will not introduce automatic substitution of generic drugs in primary care in England after a consultation showed that many people thought it posed a risk to the safety of patients and could create more work for NHS staff.

Announcing findings from a public consultation launched by the Department of Health under Labour in January ( BMJ 2010;340:c135; doi:10.1136/bmj.c135), the health minister Lord Howe said, “We know that there are valuable savings to be made from the use of generic medicines where it is clinically appropriate. However, …