tbuckley/cabot-search huggingface dataset:
Prevalence of multiple sclerosis in a south London borough.
Authors: E S Williams, R O McKeran
Journal: BMJ (1986)

A survey of multiple sclerosis in the London Borough of Sutton, population 169,600, yielded 195 cases, giving an overall prevalence of 115/100,000. This is the third highest prevalence for a first survey of a geographical area in the United Kingdom, exceeded only by 127/100,000 in north east Scotland and 134/100,000 in Shetland. On the classification system of Allison and Millar, three quarters of the cases were classified as probable multiple sclerosis, 15% as early probable and latent multiple sclerosis, and 10% as possible multiple sclerosis. The mean age was 49 years, the mean age at onset was 34 years, and the mean duration of the disease was 15.4 years. The age standardised female to male ratio was 2:1. The prevalence found in this survey does not differ significantly from that recorded in the first north east Scotland survey. This study suggests that, firstly, the prevalence of multiple sclerosis in south east England is probably about 100/100,000 and, secondly, the latitudinal effect on the prevalence of multiple sclerosis in the United Kingdom is less appreciable than previously believed.
Cbfβ interacts with Runx2 and has a critical role in bone development
Authors: Mondira Kundu, Amjad Javed, Jae-Pil Jeon, Alan Horner, Lillian Shum, Michael Eckhaus, Maximilian Muenke, Jane B. Lian, Yingzi Yang, Glen H. Nuckolls, Gary S. Stein, P. Paul Liu
Journal: Nature Genetics (2002)
The Forest for the Trees: A Systems Approach to Human Health Research
Authors: Julia M. Gohlke, Christopher J. Portier
Journal: Environmental Health Perspectives (2007)

We explore the relationship between current research directions in human health and environmental and public health policy. Specifically, we suggest there is a link between the continuing emphasis in biomedical research on individualized, therapeutic solutions to human disease and the increased reliance on individual choice in response to environmental and/or public health threats. We suggest that continued research emphasis on these traditional approaches to the exclusion of other approaches will impede the discovery of important breakthroughs in human health research necessary to understand the emerging diseases of today. We recommend redirecting research programs to interdisciplinary and population-focused research that would support a systems approach to fully identifying the environmental factors that contribute to disease burden. Such an approach would be able to address the interactions between the social, ecological, and physical aspects of our environment and explicitly include these in the evaluation and management of health risks from environmental exposures.
Abstract 452: The hypoxic response is differentially regulated in small cell lung carcinoma (SCLC) cells as compared to non-SCLC cells
Authors: Matilda Persson, Martin Johansson, Nastaran Monsef, Maria Planck-Sturegård, Sven Påhlman, Helen M. Pettersson
Journal: Cancer Research (2010)

Abstract Here we study the adaptive capacity of small cell lung carcinoma (SCLC) cells to hypoxia and the importance of activation of hypoxia-inducible factor (HIF) transcription factors in these cells. SCLC is an extremely aggressive tumor form and the 5-year survival rate for these patients is only approximately 9-15%. Regions of hypoxia (∼1% oxygen) often appear in solid tumors and are associated with aggressive tumor behaviour and poor outcome in several tumor forms. Tumor cells adapt to a hypoxic environment by changing the transcription of genes involved in a variety of processes, like angiogenesis, cell survival, and metabolism. This adaptive response is primarily regulated by the transcription factors HIF-1α and HIF-2α, which become stable at low oxygen levels. Studies using among others neuroblastoma, breast carcinoma and lung adenocarcinoma cells have demonstrated that HIF-1α primarily mediates the acute hypoxic response, whereas HIF-2α dominates during the more chronic phase of hypoxia. We investigated cell survival in a panel of SCLC cell lines cultured at different oxygen pressures. In these cells we also studied expression levels of well known hypoxia-driven genes using quantitative real-time PCR. Quantitative real-time PCR, Western blot and immunohistochemistry were used to characterise the expression of HIF transcription factors in SCLC cells as well as in SCLC specimens. In all experiments a panel of non-SCLC cells and neuroblastoma cells were included for comparison. Since tumor hypoxia correlates with poor prognosis it is important to elucidate how tumor cells adapt in response to hypoxia. Our results show that SCLC cells survive well at hypoxia, although the proliferation is somewhat reduced with lower oxygen pressure. Even though the SCLC cells have a high adaptive capacity, only a moderate up-regulation was observed for the investigated hypoxia-regulated genes at 1% oxygen. In addition, the expression patterns of HIF-1α and HIF-2α differ in SCLC as compared to non-SCLC, indicating that a “typical” adaptive response to hypoxia does not occur in SCLC cells. Based on these results a gene expression profile of hypoxic SCLC cells using microarray analyses are performed to further characterise the hypoxic adaptive response. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 452.
Human platelet-derived growth factor stimulates prostaglandin synthesis by activation and by rapid de novo synthesis of cyclooxygenase.
Authors: A J Habenicht, M Goerig, J Grulich, D Rothe, R Gronwald, U Loth, G Schettler, B Kommerell, R Ross
Journal: Journal of Clinical Investigation (1985)

Human platelet-derived growth factor (PDGF) stimulated prostaglandin (PG) E2 synthesis in the cell cycle of Swiss 3T3 cells at two distinct time intervals, with a first plateau within 10 min and a second plateau within 2-4 h after addition of PDGF. At 4 h, the concentration of PGE2 in PDGF-stimulated cultures exceeded the quiescent control cells by a factor of 10-15. Quiescent cells incubated with up to 16 microM exogenous arachidonic acid (AA) synthesized only small amounts of PGE2. In contrast, 4 h after addition of PDGF, the concentration of PGE2 synthesized from exogenous AA exceeded that in quiescent cultures by a factor of 28. The effect of PDGF stimulation on PG synthesis from exogenous AA could not be explained by growth factor-mediated increase in the cellular free AA pool as shown in experiments using [14C]AA. PDGF also stimulated synthesis of PGI2 (prostacyclin), thromboxane, and PGF2 alpha from exogenous AA. While inhibition of protein synthesis by 10 micrograms/ml cycloheximide had no effect on the early increase in PGE2 synthesis, the second increase was completely prevented. Additionally, cycloheximide treatment at 6 h after PDGF stimulation resulted in rapid decline of PGE2 synthesis from exogenous AA. Quiescent cultures pretreated with 100 microM aspirin and stimulated by PDGF thereafter recovered from cyclooxygenase inhibition within 180 min. Our results suggest that phospholipase activation and resultant AA release is not sufficient to induce the burst of PG synthesis observed in PDGF-stimulated cells. Instead, PDGF stimulates PG synthesis by direct effects on the PG-synthesizing enzyme system, one involving a protein synthesis-independent mechanism and another that requires rapid translation of cyclooxygenase.
Identification of non-catalytic matrix metalloproteinase 1 residues that participate in collagenolysis.
Authors: JL Lauer-Fields, GB Fields
Journal: Cancer Research (2009)

Abstract Abstract #2063 Collagen serves as a structural scaffold and a barrier between tissues, and thus collagen catabolism (collagenolysis) is required to be a tightly regulated process in normal physiology. In turn, the destruction or damage of collagen during pathological states plays a role in tumor growth and invasion, cartilage degradation, or atherosclerotic plaque formation. Only a small number of proteases have been identified capable of efficient processing of triple-helical regions of collagens. Several members of the zinc metalloenzyme family, specifically matrix metalloproteinases (MMPs), possess collagenolytic activity, and at least one of these (MMP-1) has been strongly implicated in the progression of breast cancer. The present study has utilized triple-helical peptide (THP) substrates and inhibitors to dissect MMP-1 collagenolytic behavior. Analysis of MMP-1/THP interactions by hydrogen/deuterium exchange mass spectrometry (HDX MS) in combination with site-specific mutagenesis and enzyme kinetic assays have allowed us to identify non-catalytic sites in MMP-1 that participate in collagenolysis. As we have recently demonstrated [J. Am. Chem. Soc. 129, 10408 (2007)], non-catalytic sites can be utilized to create THP inhibitors that target proteases implicated in cancer progression while sparing proteases with host-beneficial functions. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2063.
Regulation of G protein-coupled receptor kinase subtypes in activated T lymphocytes. Selective increase of beta-adrenergic receptor kinase 1 and 2.
Authors: A De Blasi, G Parruti, M Sallese
Journal: Journal of Clinical Investigation (1995)

Beta-adrenergic receptor kinase (beta ARK) is a serine-threonine kinase involved in the process of homologous desensitization of G-coupled receptors. beta ARK is a member of a multigene family, consisting of six known subtypes, also named G protein-coupled receptor kinases (GRK 1-6). In this study we investigated the expression of GRKs during the process of T cell activation, which is of fundamental importance in regulating immune responses. T cell activation was induced by exposing mononuclear leukocytes (MNL) to PHA and confirmed by tritiated thymidine incorporation measurement. A substantial increase of GRK activity (as measured by in vitro phosphorylation of rhodopsin) was found after 48 h (331 +/- 80% of controls) and 72 h (347 +/- 86% of controls) of exposure to PHA. A threefold increase of beta ARK1 immunoreactivity was found in MNL exposed to PHA for 72 h. Persistent activation of protein kinase C (PKC) by 10 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) was able to increase beta ARK activity to the same extent as PHA, suggesting a PKC-mediated mechanism. The kinetic of beta-adrenergic-stimulated cAMP production was substantially modified in TPA and PHA-activated cells, indicating that the increased GRK activity resulted in an increased beta-adrenergic homologous desensitization. A three- to fourfold increase in GRK activity was also observed in a population of T cell blasts (> 97% CD3+) exposed to PHA for 48-72 h. A significant increase in beta ARK1 and beta ARK2 mRNA expression was observed 48 h after mitogen stimulation, while mRNA expression of GRK5 and GRK6 was not changed. In conclusion our data show that the expression of GRK subtypes is actively and selectively modulated according to the functional state of T lymphocytes.
Mother-to-infant transmission of hepatitis B virus infection: Significance of maternal viral load and strategies for intervention
Authors: Wan-Hsin Wen, Mei-Hwei Chang, Lu-Lu Zhao, Yen-Hsuan Ni, Hong-Yuan Hsu, Jia-Feng Wu, Pei-Jer Chen, Ding-Shinn Chen, Huey-Ling Chen
Journal: Journal of Hepatology (2013)
Officials report first Cambodian case of avian flu
Authors: Jane Parry
Journal: BMJ (2005)

BACKGROUND: Children with parents who smoke are often exposed to high levels of environmental tobacco smoke, and children with asthma are particularly susceptible to the detrimental effects of passive smoking. Data were collected from parents who smoke and from their asthmatic children. The families are currently taking part in a randomised controlled trial to test an intervention designed to reduce passive smoking in children with asthma. This paper reports on the baseline data. Questionnaire data and cotinine levels were compared in an attempt to assess exposure and to identify factors which influence exposure of the children. The aim of the study was to identify the scope for a reduction in passive smoking by these children. METHODS: A sample of 501 families with an asthmatic child aged 2-12 years was obtained. Factors influencing passive smoking were assessed by interviewing parents. Cotinine levels were measured from saliva samples using gas liquid chromatography with nitrogen phosphorous detection. RESULTS: Cotinine levels in children were strongly associated with the age of the child, the number of parents who smoked, contact with other smokers, the frequency of smoking in the same room as the child, and crowding within the home. Parental cotinine levels, the amount smoked in the home, and whether the home had a garden also exerted an independent effect on cotinine levels in the children. CONCLUSIONS: Many children are exposed to high levels of environmental tobacco smoke and their cotinine levels are heavily dependent upon proximity to the parent who smokes. Parents who smoke have a unique opportunity to benefit their child9s health by modifying their smoking habits within the home.
Immunosuppression using the mTOR inhibition mechanism affects replacement of rat liver with transplanted cells
Authors: Yao-Ming Wu, Brigid Joseph, Sanjeev Gupta
Journal: Hepatology (2006)

Successful grafting of tissues or cells from mismatched donors requires systemic immunosuppression. It is yet to be determined whether immunosuppressive manipulations perturb transplanted cell engraftment or proliferation. We used syngeneic and allogeneic cell transplantation assays based on F344 recipient rats lacking dipeptidyl peptidase IV enzyme activity to identify transplanted hepatocytes. Immunosuppressive drugs used were tacrolimus (a calcineurin inhibitor) and its synergistic partners, rapamycin (a regulator of the mammalian target of rapamycin [mTOR]) and mycophenolate mofetil (an inosine monophosphate dehydrogenase inhibitor). First, suitable drug doses capable of inducing long-term survival of allografted hepatocytes were identified. In pharmacologically effective doses, rapamycin enhanced cell engraftment by downregulating hepatic expression of selected inflammatory cytokines but profoundly impaired proliferation of transplanted cells, which was necessary for liver repopulation. In contrast, tacrolimus and/or mycophenolate mofetil perturbed neither transplanted cell engraftment nor their proliferation. Therefore, mTOR-dependent extracellular and intracellular mechanisms affected liver replacement with transplanted cells. In conclusion, insights into the biological effects of specific drugs on transplanted cells are critical in identifying suitable immunosuppressive strategies for cell therapy.
Minitracheotomy: a simple alternative to tracheostomy in obstructive sleep apnoea.
Authors: A Hasan, J McGuigan, M D Morgan, H R Matthews
Journal: Thorax (1989)

A patient with obstructive sleep apnoea sufficiently severe to cause papilloedema was managed temporarily with a minitracheotomy. This allowed arterial oxygen saturation to return to normal while he lost weight, before surgery for his enlarged tonsills.
Coumadin (Warfarin) Sodium
Authors: Joseph H. Nicholson, Thomas Leavitt
Journal: New England Journal of Medicine (1956)

THE introduction of bishydroxycoumarin (Dicumarol) about fifteen years ago evoked a voluminous literature on the use of anticoagulant treatment for the prevention and control of thrombotic and thromboembolic disorders. The early reports demonstrated that Dicumarol, by virtue of its depressing effect on the level or activity of plasma prothrombin, was an effective in vivo anticoagulant that could be usefully employed for the treatment of thrombosis and thromboembolism — particularly venous thrombosis and pulmonary embolism. These experiences also brought to light certain shortcomings of the drug.A number of reports dealt with the prothrombin-depressing properties of congeners of the original Dicumarol. . . .
Propranolol in black hypertensives.
Authors: D G Delvin
Journal: BMJ (1978)

sort of figure that surgical results must be balanced.While late surgery in a younger person must take account of the risks of rebleeding in the very long term,3 this is obviously not so in the elderly, whose mean expectation of life is in any case limited.It is not valid to compare the treatment of an aneurysmal subarachnoid haemorrhage with that of a fractured hip, an intestinal obstruction, or a dissecting aneurysm in an old person.Patients with the latter conditions will die if left untreated.Most patients with a ruptured aneurysm who survive the first haemorrhage and the next few weeks will recover to resume a normal life without any surgical treatment.
“I Swear by Apollo” — On Taking the Hippocratic Oath
Authors: Howard Markel
Journal: New England Journal of Medicine (2004)

Every spring for almost 20 years, I have happily donned a rented robe, hood, and mortarboard to attend medical school commencement exercises. The purpose of this annual foray into pomp and circumstance goes well beyond applauding the achievements of graduates who are about to enter the medical profession. For me, commencement is the perfect opportunity to renew my vows, as it were, standing shoulder to shoulder with both newly minted doctors and like-minded colleagues as we take the Hippocratic Oath.Although many scholars dispute the exact authorship of the writings ascribed to the ancient physician Hippocrates, who probably lived sometime . . .
Interaction of Exercise and Insulin in Type II Diabetes Mellitus
Authors: Harriet Wallberg-Henriksson
Journal: Diabetes Care (1992)

In skeletal muscle, at the level of glucose transport, insulin resistance appears to be a major alteration responsible for decreased glucose disposal rates in non-insulin-dependent (type II) diabetes mellitus. This study focuses on in vitro studies of the glucose transport process in human and rat skeletal muscle. Muscle strips from a group of lean type II diabetic patients demonstrated a 50% decrease in insulin responsiveness for glucose transport when compared with nondiabetic subjects. These findings indicate the presence of postreceptor defects in type II diabetic muscles. Furthermore, in an isolated muscle preparation, it could be demonstrated that epitrochlearis muscles from streptozocin-induced diabetic rats were not only resistant to insulin, but also to exercise-induced increase in glucose transport. However, both regular physical exercise and insulin therapy normalized the decreased capacity for glucose transport in the diabetic rat muscles. Therefore, it appears that regular physical exercise and, in some cases insulin therapy, would be advisable for type II diabetic patients with marked muscular insulin resistance to improve peripheral glucose disposal rates.
Health secretary promises to outlaw ageism from the NHS by 2012
Authors: Z. Kmietowicz
Journal: BMJ (2009)

Age discrimination in the NHS and social care will become illegal in 2012, the health secretary has vowed.

Andy Burnham was speaking at the national children and adult services conference in Harrogate on 22 October when he responded to the publication of a review on age discrimination and age equality in the health and social sector published the same day.

Mr Burnham said that health and social services were “taking great strides” to break down assumptions about age in several programmes, such as the national dementia strategy. But he added, “I think we all agree there’s further to go. I’m therefore supporting the recommendation that Sir Ian Carruthers and Jan Ormondroyd make in today’s age discrimination review. Specifically that the age discrimination ban in the Equality Bill should apply for health and social care across England, Wales, and Scotland at the same time as other sectors—in 2012”

He added, “Meeting that deadline is ambitious, …
Accelerated Insulin Degradation: An Alternate Mechanism for Insulin Resistance
Authors: Abbas E Kitabchi, Frankie B Stentz, Cindy Cole, William C Duckworth
Journal: Diabetes Care (1979)

We have examined insulin and glucagon degrading activities of muscle and fat tissues in 11 subjects (4 lean controls, 3 insulin-resistant obese subjects, 2 non-insulin-dependent diabetic subjects, and 2 insulin-treated diabetic subjects) and correlated degrading activity with (1) basal insulin level and (2) state of insulin resistance. We found hyperinsulinemia and insulin resistance to be significantly correlated with accelerated insulin and glucagon degrading activity. Weight reduction in an insulin-resistant obese patients results in parallel reduction in both basal insulin level and insulin–glucagon degrading activity. These data are consistent with the hypothesis that an alternative mechanism for insulin resistance may be an accelerated insulin degradation at the level of target tissues.
Abstract P6-02-03: The Use of Charcoal Suspension Labeling as an Adjunct in the Detection of Non-Palpable Breast Lesions
Authors: TC Santos Cavalcanti, VM Budel, P. Gasperin
Journal: Cancer Research (2010)

Abstract Introduction and Objectives: Inert charcoal suspension is used as a tissue marker, which provides innumerous advantages over other labeling methods and techniques, such as dyes and metallic needles. In addition, the use of charcoal does not present problems with regards to its diffusion, labeling the trajectory from the lesion to the skin, being easily identified by both the surgeon and pathologist. The occurrence of morphological alterations due to the use of charcoal is very rare. In contrast, there are still doubts and questions concerning the interference of charcoal labeling with regards to the anatomopathological diagnosis accuracy. The main objectives in this study are to analyze the efficiency of labeling impalpable breast lesions with inert charcoal suspension; to evaluate the morphological alterations associated with its use and to determine whether the use of charcoal labeling hampers with the diagnostic interpretation of the pathologist. Materials and Methods: The study evaluated a total of 135 cases of impalpable breast lesions, previously labeled with charcoal suspension. Histological H/E stained slides containing charcoal pigments were analyzed using optical microscopy, by which both quantitative and qualitative evaluations with regards to inflammatory response and interference in diagnosis were performed. Lymphocyte, giant cells and neutrophils were evaluated and quantified. Moreover, the distribution of the charcoal suspension present in the lesions was evaluated. Results: As to the quantitative and qualitative evaluation of the inflammatory response caused by the use of charcoal labeling, it was observed that granulomas were present in all samples, regardless of the quantity of injected charcoal. Lymphocytic inflammatory response was absent in 5.19% of the samples only, were 82.22% demonstrated discrete intensity and 12.59% was moderate. With regards to acute inflammatory response, 42.96% showed total absence of neutrophilic exudate, were as 42.22% demonstrated discrete and 11.11% moderate, and only 3.7% of cases were intense. Conclusion: This study corroborates the utility and easiness of the charcoal method as a means of efficient labeling of impalpable breast lesions. In addition, this technique is easy to use, has a low cost, high efficiency and does not interfere with the histological analysis. Moreover, it is comfortable for the patient and is of great help in finding and localizing the lesions to both the surgeon and pathologist. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-02-03.