tbuckley/cabot-search huggingface dataset:
Fetal and Infant Origins of Adult Disease
Authors: Helen M. Wallace
Journal: JAMA (1993)

This book consists of articles written by 39 authors under the aegis of the British Medical Research Council and previously published in various British journals. The general theme of the 31 chapters is that factors affecting the fetus and the young child have long-lasting effects and are important causes of later diseases, such as ischemic heart disease, stroke, and chronic bronchitis. The Barker group studied the observation that areas in Britain which now have high rates of death from cardiovascular diseases (ischemic heart disease and stroke) used to have high infant death rates. Factors that were unfavorable for health in infancy might therefore also cause later disease in adult life. A detailed geographic comparison of infant mortality in the earlier part of this century with more recent adult mortality suggested that particular periods in pregnancy and infancy might have specific importance for the later development of ischemic heart disease, stroke,
Phylogenies Inferred from Mitochondrial Gene Orders—A Cautionary Tale from the Parasitic Flatworms
Authors: Thanh H. Le, David Blair, Takeshi Agatsuma, Pierre-François Humair, Nick J.H. Campbell, Mori Iwagami, D. Timothy J. Littlewood, B. Peacock, David A. Johnston, J. Bartley, David Rollinson, E.A. Herniou, Dante S. Zarlenga, Donald P. McManus
Journal: Molecular Biology and Evolution (2000)

[Extract] Mitochondrial genomes have been used in numerous studies to investigate phylogenetic relationships among eukaryotes at many levels (e.g., Smith et al. 1993; Boore et al. 1995; Boore, Lavrov, and Brown 1998). In recent years, the arrangement of genes in the mitochondrial genome has been regarded as a powerful record of historical relationships (Boore 1999). Changes in mitochondrial gene order are infrequent, even over considerable spans of time (Boore 1999), and are unlikely to exhibit homoplasy. Our research has focused on the relationships between two groups of human blood flukes within the genus Schistosoma. Our investigations on the mitochondrial genomes of these worms revealed striking divergences in mitochondrial gene order within the genus.

The schistosomes are among the most significant parasites of humans in the developing world. The disease they cause, schistosomiasis, is second only to malaria in public health importance, affecting some 200 million people in 75 countries and giving rise to severe morbidity or mortality in tens of millions. Recent molecular studies (Barker and Blair 1996) have demonstrated that the deepest split in the genus is between East the Asian species utilizing prosobranch snail hosts and the African species utilizing pulmonate snails. The depth of this split has led some authors to propose an early Tertiary divergence (Despres et al. 1992). Species closely allied with the African group also occur in the Middle East, India, and parts of Southern Asia. One African species, Schistosoma mansoni, was probably introduced into the Americas by the slave trade during the 18th and 19th centuries (Despres, Imbert-Establet, and Monnerot 1993). The Asian group contains fewer recognized species, and these are found primarily in East Asia (the Philippines, China, Malaysia, Indonesia, Cambodia, and Laos). There is a growing realization that African and East Asian schistosomes differ in many biological attributes, including morphological characters, infectivity to snails, range of definitive hosts, growth rates, egg production, prepatency periods, pathogenicity, and immunogenicity (McManus and Hope 1993). We expected our investigations of mitochondrial genomes in these two groups of species to provide more evidence of their phylogenetic distance. However, we were startled by the remarkable differences in mitochondrial gene order which came to light between the two groups and which we report here.
William Benjamin Clee
Authors: P. Clee
Journal: BMJ (2008)

[<sup>18</sup>F]Fluorodeoxyglucose ([<sup>18</sup>F]FDG), a glucose analogue, has been widely used for tumor imaging. To investigate the mechanisms related to [<sup>18</sup>F]FDG uptake by tumors, an experiment involving nude mice was performed. <b>Methods:</b> Human colon cancer cell lines SNU-C2A, SNU-C4 and SNU-C5 were transplanted to nude mice. Using immunohistochemical staining and Western blot, the expression of glucose transporter (Glut) isoforms (Glut-1∼5) in xenografted tumors was analyzed. For the analysis of messenger ribonucleic acid (mRNA) expression, reverse-transcription polymerase chain reaction and Northern blot were used and the enzyme activity of hexokinase in cancer tissues was measured by continuous spectrophotometric rate determination. <b>Results:</b> [<sup>18</sup>F]FDG uptake in SNU-C4 and SNU-C5 cells was higher than in normal colon cells. Among these cells and xenografted tumors, SNU-C5 showed the highest level of [<sup>18</sup>F]FDG uptake, followed by SNU-C4 and SNU-C2A. An immunostamning experiment showed intense staining of Glut-1 in SNU-C5 tumors but somewhat faint staining in SNU-C4. SNU-C5 tumors also showed positive staining with Glut-3, although this was not the case with SNU-C2A and SNU-C4. Western blot analysis showed the expression of Glut-1 and Glut-3 in all tumors. Experiments involving Northern blot analysis and reverse transcription polymerase chain reaction confirmed the overexpression of Glut-1 mRNA in all tumors, with the highest level in SNU-C5. The level of Glut-3 mRNA was also elevated in SNU-C5 tumors but not in SNU-C2A and SNU-C4. The enzyme activity of hexokinase did not vary among different tumors. <b>Conclusion:</b> Gluts, especially Glut-1, are responsible for [<sup>18</sup>F]FDG uptakein a nude mouse model of colon cancer rather than hexokinase activity. Increased numbers of glucose transporters at the plasma membrane of cancer cells is attributed to an increased level of transcripts of glucose transporter genes and may be a cause of increased [<sup>18</sup>F]FDG uptake, at least in colon cancer tumors.
Abstract 1419: Role of p70S6K in breast cancer recurrence
Authors: Barbara Belletti, Maura Sonego, Stefania Berton, Tiziana Perin, Samuele Massarut, Gustavo Baldassarre
Journal: Cancer Research (2011)

Abstract In Early Breast Cancer (EBC) a single dose of intraoperative radiotherapy with TARGIT (Targeted Intraoperative RadioTherapy) protocol is as effective as the standard therapy in the control of local recurrences (Vaidya et al. Lancet, 376: 91-102, 2010). We recently demonstrated that TARGIT treatment affects the tumor microenvironment, after breast conserving surgery, by altering the local production of several growth factors and cytokines. Eventually, these changes in the proteomic profile, result in a lower activation of the p70S6K pathway in breast cancer cells (Belletti et al. CCR, 14: 1325-32, 2008). To dissect the role of p70S6K in breast cancer cells proliferation, motility and invasion, we generated genetically modified human breast cancer cell lines expressing specific shRNA or carrying a dominant negative form of p70S6K (p70KR) and tested their ability to grow and migrate, first in vitro then in vivo. Growth curve experiments on MDA MB 231 and MDA MB 453 mammary carcinoma cells, demonstrated that expression of the p70KR mutant slightly reduced the growth rate of these cells. The same cells have been also characterized for their ability to migrate in 2D- and 3D-contexts, in response to the wound fluids harvested from EBC patients as chemoattractants, showing that p70KR reduced their ability to invade. Next, we moved to an in vivo model to evaluate more in detail the involvement of p70S6K in the local recurrence of breast cancer. To this aim, parental or p70S6K genetically modified breast cancer cells have been injected in female nude mice mammary fat pads. Two weeks later, the tumor was removed by surgical excision and the mice observed for the appearance of recurrences. Macroscopic and histo-pathological examination of the primary tumors revealed that despite formation of similar masses, only tumors derived from parental cells displayed lymph-vascular invasion. More importantly, only mammary pads injected with parental cells developed recurrent disease and, at pathological analysis, displayed nodal metastasis. Altogether these data highlight a crucial function of p70S6K in the formation of local recurrence in breast cancers, and support the hypothesis that, in EBC patients, an anti-p70S6K specific therapy may be useful for the prevention of local recurrences. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1419. doi:10.1158/1538-7445.AM2011-1419
FURTHER REMARKS ON THE MIXED TYPHOID + PARATYPHOID A + PARATYPHOID B VACCINE
Authors: A. Castellani
Journal: BMJ (1915)

EMDIX3E) TPYIOIIOID AND PARATYPIIOID VACCINE.[MIAY T, 19I5 present, as far as mny exzperience aocs, aild is one of the last symiptomiis to disappear as t-lic patielnt recovers.Its disappearancee is a good sign, its rcappearance is an indication of a recru(lesence of tlle, disease.Unfortuniately the disease is very treaclherouis, and recrtudescences or relapses ar'e very liable to ocCur.The raslhes are very usefutl aids to diagnosis.1.The pink spots are iiot tilulile thlose of typlhoid, bult are not usuially raisec(.Tlhey are miore frequiently found on tlhe back and abouit the joiints.
Partial Impairment of Cytokine Responses in Tyk2-Deficient Mice
Authors: Marina Karaghiosoff, Hans Neubauer, Caroline Lassnig, Pavel Kovarik, Heike Schindler, Hanspeter Pircher, Barbara McCoy, Christian Bogdan, Thomas Decker, Gottfried Brem, Klaus Pfeffer, Mathias Müller
Journal: Immunity (2000)
Cell behavior and signal molecule involvement in a case study of malignant histiocytosis: A negative model of morphine as an immunoregulator
Authors: Gregory L. Fricchione, Lawrence Cytryn, Thomas V. Bilfinger, George B. Stefano
Journal: American Journal of Hematology (1997)

In a patient diagnosed with histiocytic medullary reticulosis (HM), we examined immunocytes for their responsiveness towards known signaling molecules. Both the granulocytes and monocytes were found to exhibit a high level of spontaneous activation (96% compared to normal cells 7%; P < 0.001). These cells could not be downregulated when exposed to morphine. Following patient treatment with doxorubicin and cyclophosphamide, the immunocytes still exhibited a high spontaneous activation. They responded to morphine exposure in vitro with a cell rounding and becoming immobile for only 20 min whereas normal cells would remain round and immobile for up to 1–2 h. An examination of the plasma from the HM patient revealed that monocyte colony stimulating factor (MCSF) levels were elevated (6.4 and 5.78 compared to a control range of 1–1.75 ng/ml). In the HM patient, the immunocytes did not express the opiate selective and opioid peptide insensitive receptor, μ3, supporting the lack of opiate action. Given this finding, we incubated normal monocytes with MCSF and found that it significantly reduced the μ3 Bmax. Given the role of intracellular calcium in the activation process of immunocytes, we examined the action of various calcium channel blockers for their ability to inhibit the activated HM monocytes. The agents (nimodipine, cardiazem, and verapamil; 10−9 M) were able to inhibit the HM-associated chemokinesis. Taken together, the data indicate that in the HM patient the immunocytes appear to be overactivated because stimulatory molecules are high and have the ability to downregulate the normal “braking” process. Additionally, the data indicate that MCSF deregulation may be involved as an initiating factor for this disorder. Am. J. Hematol. 56:197–205, 1997. © 1997 Wiley-Liss, Inc.
Monoclonal Antibody Against Tissue Factor Shortens Tissue Plasminogen Activator Lysis Time and Prevents Reocclusion in a Rabbit Model of Carotid Artery Thrombosis
Authors: Massimo Ragni, Plinio Cirillo, Immacolata Pascucci, Annalisa Scognamiglio, Davide D’Andrea, Nicola Eramo, Michael D. Ezekowitz, Aruna B. Pawashe, Massimo Chiariello, Paolo Golino
Journal: Circulation (1996)

Background Tissue factor (TF)–dependent activation of the coagulation is important in the pathophysiology of intravascular thrombus formation. We tested the effects of a monoclonal antibody against TF (AP-1) on lysis time induced by tissue-type plasminogen activator (TPA) and on reocclusion rate in a rabbit model of carotid artery thrombosis. Methods and Results Intravascular thrombosis was obtained by placing an external constrictor around carotid arteries with endothelial injury. Carotid blood flow velocity was measured continuously with a Doppler flow probe. Thirty minutes after thrombus formation, the rabbits received either AP-1 (0.15 mg/kg IV, n=8) or placebo (n=8). All rabbits also received TPA (80 μg/kg bolus plus 8 μg·kg −1 ·min −1 infusion for up to 90 minutes or until reperfusion was achieved) and heparin (200 U/kg IV as a bolus). At reperfusion, TPA was discontinued, and the rabbits were followed for an additional 90 minutes. AP-1 shortened lysis time from 44±8 minutes (mean±SEM) in control rabbits to 26±7 minutes in AP-1–treated rabbits ( P &lt;.01). Reocclusion occurred in all control rabbits in 10±3 minutes, whereas it occurred in only two of eight AP-1–treated rabbits in 72 and 55 minutes ( P &lt;.01). No changes in prothrombin time and ex vivo platelet aggregation in response to various agonists were observed after AP-1 administration, indicating the absence of systemic effects by this antibody. Conclusions TF exposure and activation of the extrinsic coagulation pathway play an important role in prolonging lysis time and mediating reocclusion after thrombolysis in this model. AP-1, a monoclonal antibody against TF, might be suitable as adjunctive therapy to TPA.
Drug- and mutagenesis-induced changes in the selectivity filter of a cardiac two-pore background K channel
Authors: P HAJDU, C ULENS, G PANYI, J TYTGAT
Journal: Cardiovascular Research (2003)

Objective: As compared with voltage-gated K+ channels (Kv-type), our knowledge of the structure-function and pharmacology of two-pore background K+ channels is still very limited. Here we have used a drug- and mutagenesis-based approach to study the effect of the antidepressant fluoxetine (FL) and analgesic d-norpropoxyphene (NORP) on the cardiac two-pore background K+ channel. Methods: Whole-cell currents of the cTBAK-1 channel expressed in Xenopus laevis oocytes were investigated using conventional two-microelectrode voltage-clamp recording method combined with functional mutagenesis of the channel protein. Results: Both drugs inhibit cTBAK-1 current: FL proved to be a voltage-dependent pore-blocker, while NORP induced a change in the selectivity of cTBAK-1 giving rise to a shift in the reversal potential (Erev) toward more positive voltages due to an increased Na+ permeability. Mutations were introduced into the selectivity filter of the first (Y105F) and the second (F211Y) pore to mimic the P-region of HERG (GFGN) and Kv1.1 (GYGD) channels. Point mutations in the channel resulted in two distinct phenotypes of cTBAK-1: the mutant Y105F channel lost its selectivity and was unaffected by NORP, in contrast to the F211Y mutant. Conclusion: FL and NORP block the current of cTBAK-1 channels differently, the latter modified the selectivity of the channel pore. Our mutagenesis study revealed that NORP interacts with the selectivity filter of cTBAK-1. The significant role of the GYGD motif in this type of K+ channels is emphasized.
Effects of n-acetylcysteine in a rat model of ischemia and reperfusion injury
Authors: S Cuzzocrea
Journal: Cardiovascular Research (2000)

Objective: Splanchnic artery occlusion shock (SAO) causes an enhanced formation of reactive oxygen species (ROS), which contribute to the pathophysiology of shock. Here we have investigated the effects of n-acetylcysteine (NAC), a free radical scavenger, in rats subjected to SAO shock. Methods and results: Treatment of rats with NAC (applied at 20 mg/kg, 5 min prior to reperfusion, followed by an infusion of 20 mg/kg/h) attenuated the mean arterial blood and the migration of polymorphonuclear cells (PMNs) caused by SAO-shock. NAC also attenuated the ileum injury (histology) as well as the increase in the tissue levels of myeloperoxidase (MPO) and malondialdehyde (MDA) caused by SAO shock in the ileum. There was a marked increase in the oxidation of dihydrorhodamine 123 to rhodamine in the plasma of the SAO-shocked rats after reperfusion. Immunohistochemical analysis for nitrotyrosine and for poly(ADP-ribose) synthetase (PARS) revealed a positive staining in ileum from SAO-shocked rats. The degree of staining for nitrotyrosine and PARS were markedly reduced in tissue sections obtained from SAO-shocked rats which had received NAC. Reperfused ileum tissue sections from SAO-shocked rats showed positive staining for P-selectin, which was mainly localised in the vascular endothelial cells. Ileum tissue section obtained from SAO-shocked rats with anti-intercellular adhesion molecule (ICAM-1) antibody showed a diffuse staining. NAC treatment markedly reduced the intensity and degree of P-selectin and ICAM-1 in tissue section from SAO-shocked rats. In addition, in ex vivo studies in aortic rings from shocked rats, we found reduced contractions to noradrenaline and reduced responsiveness to a relaxant effect to acetylcholine (vascular hyporeactivity and endothelial dysfunction, respectively). NAC treatment improved contractile responsiveness to noradrenaline, enhanced the endothelium-dependent relaxations and significantly improved survival. Conclusion: Taken together, our results clearly demonstrate that NAC treatment exert a protective effect and part of this effect may be due to inhibition of the expression of adhesion molecule and peroxynitrite-related pathways and subsequent reduction of neutrophil-mediated cellular injury.
Hip Fracture Management
Authors: K Hardinge
Journal: BMJ (1994)

Martyn J Parker, Glyn A Pryor Blackwell Scientific, £ 69.50, pp 292 ISBN 0-632-03263-4

An ambitious undertaking, Hip Fracture Management represents the work of the Peterborough hip fracture project, which was set up by John Myles, formerly consultant orthopaedic surgeon at Peterborough District General Hospital. It is spectacularly successful. Fractures of the proximal femur …
Hypertrophy and functional alterations in hyperdynamic phospholamban-knockout mouse hearts under chronic aortic stenosis
Authors: H Kiriazis
Journal: Cardiovascular Research (2002)

To determine whether the hyperdynamic phospholamban-knockout hearts are capable of withstanding a chronic aortic stenosis.The transverse section of the aorta was banded in phospholamban-knockout and their isogenic wild-type mice, which were followed with echocardiography in parallel, along with sham-operated mice, before and at 2.5, 5 and 10 weeks after surgery.Cardiac decompensation was evidenced by the presence of lung congestion in some banded knockouts and wild-types, giving rise to a subset of non-failing and failing hearts within each group. The incidence of heart failure was not genotype-dependent but rather associated with higher heart rates before surgery. The development of left ventricular hypertrophy was similar between knockouts and wild-types and longitudinal assessment of end-diastolic dimension indicated progressive increases after banding, with a greater dilation in failing mice. Fractional shortening was reduced in failing knockouts and wild-types to a similar degree, with an earlier onset in the knockouts. In addition, fractional shortening was decreased in non-failing knockouts but not wild-types. Ejection times shortened after aortic banding particularly for failing hearts. Assessment of the SR Ca(2+)-ATPase protein levels indicated similar downregulation for failing knockouts and wild-types, while the phospholamban levels were not significantly altered in wild-types.The hyperdynamic phospholamban-knockout hearts are able to compensate against a sustained aortic stenosis similar to wild-types.
Soft tissue mass around the shoulder
Authors: H S Reid, E McNally, A Carr
Journal: Annals of the Rheumatic Diseases (1998)

Clinical historyA previously fit 47 year old female school teacher presented with a six month history of a painful swelling over her right shoulder.There was rapid development of the swelling initially, which then stabilised.On examination she was apyrexial with a large, firm, non-tender mass around the right shoulder, which clinically had some cystic features.There was no significant limitation of movement.Other findings on clinical examination included some minor soft tissue capsular swelling of the second and third metacarpophalangeal joints of the right hand.Otherwise the remainder of the locomotor system was normal.Her erythrocyte sedimentation rate was increased at 51 mm 1st h, but C reactive protein remained normal at <0.6.Full blood count was normal with a haemoglobin of 13.4 g/dl, white blood cell count 7.5 × 10 9 /l, platelet count 424 ×10 9 /l.The rheumatoid factor, however, was positive with a titre of 1:1280.
THE PALLIATIVE TREATMENT OF CANCER OF THE CERVIX UTERI AND BLADDER IN WOMEN.
Authors: NATHAN G. BOZEMAN
Journal: JAMA (1897)

I shall confine my remarks to the treatment of carcinoma of the cervix uteri and the bladder in the stage of the disease when any operative measure may be of doubtful expedience, or in cases where operations have been undertaken and the disease still progresses, the condition of the patients being most distressing from hemorrhage, sepsis, incontinence of urine and all the evils resulting therefrom. My interest has been aroused in this class of patients, and no doubt you feel the same, because of their hopeless condition and the difficulty of caring for them in our public hospitals. Certainly, treatment will be directed to alleviating their suffering and rendering their surroundings as wholesome as possible. Women afflicted with inoperable epithelioma of the cervix uteri, when they are not undergoing any treatment, complain most frequently of hemorrhage and a foul-smelling, bloody discharge from the vagina. The vaginal examination reveals a hard
Career advice for doctors with a chronic illness
Authors: R. MacDonald
Journal: BMJ (2001)

Career Focus bmj.com/content/vol322/issue7295/#CAREER 

I have scleroderma. Eighteen months ago I was advised by an occupational health physician to retire from the NHS on grounds of ill health. I was 30. Determined not to let my medical skills go to waste, I was left on my own to find a niche for myself which matched my health needs and allowed me to carry on working. My situation is not unique, and in this week's Career Focus ( BMJ Classified p 2) some doctors who have chronic illnesses summarise their experiences and give advice to other doctors who may find themselves in a similar position. This week also sees the launch of Career Focus's mentoring scheme for doctors with chronic illness.

Doctors who have a chronic illness have a rough deal. As well as having to come to terms with their illness, they also face problems in their career. Inflexible working patterns, poor contingency cover, …
T cell development requires constraint of the myeloid regulator C/EBP-α by the Notch target and transcriptional repressor Hes1
Authors: Maria Elena De Obaldia, J Jeremiah Bell, Xinxin Wang, Christelle Harly, Yumi Yashiro-Ohtani, Jonathan H DeLong, Daniel A Zlotoff, Dil Afroz Sultana, Warren S Pear, Avinash Bhandoola
Journal: Nature Immunology (2013)