tbuckley/cabot-search huggingface dataset:
Shigella Targets Epithelial Tricellular Junctions and Uses a Noncanonical Clathrin-Dependent Endocytic Pathway to Spread Between Cells
Authors: Makoto Fukumatsu, Michinaga Ogawa, Satoko Arakawa, Masato Suzuki, Kazuhisa Nakayama, Shigeomi Shimizu, Minsoo Kim, Hitomi Mimuro, Chihiro Sasakawa
Journal: Cell Host & Microbe (2012)

Bacteria move between cells in the epithelium using a sequential pseudopodium-mediated process but the underlying mechanisms remain unclear. We show that during cell-to-cell movement, Shigella-containing pseudopodia target epithelial tricellular junctions, the contact point where three epithelial cells meet. The bacteria-containing pseudopodia were engulfed by neighboring cells only in the presence of tricellulin, a protein essential for tricellular junction integrity. Shigella cell-to-cell spread, but not pseudopodium protrusion, also depended on phosphoinositide 3-kinase, clathrin, Epsin-1, and Dynamin-2, which localized beneath the plasma membrane of the engulfing cell. Depleting tricellulin, Epsin-1, clathrin, or Dynamin-2 expression reduced Shigella cell-to-cell spread, whereas AP-2, Dab2, and Eps15 were not critical for this process. Our findings highlight a mechanism for Shigella dissemination into neighboring cells via targeting of tricellular junctions and a noncanonical clathrin-dependent endocytic pathway.
Sex hormones and hypertension
Authors: R Dubey
Journal: Cardiovascular Research (2002)

Gender has an important influence on blood pressure, with premenopausal women having a lower arterial blood pressure than age-matched men. Compared with premenopausal women, postmenopausal women have higher blood pressures, suggesting that ovarian hormones may modulate blood pressure. However, whether sex hormones are responsible for the observed gender-associated differences in arterial blood pressure and whether ovarian hormones account for differences in blood pressure in premenopausal versus postmenopausal women remains unclear. In this review, we provide a discussion of the potential blood pressure regulating effects of female and male sex hormones, as well as the cellular, biochemical and molecular mechanisms by which sex hormones may modify the effects of hypertension on the cardiovascular system.
REACTIVITY OF RENAL AND SYSTEMIC CIRCULATIONS TO VASOCONSTRICTOR AGENTS IN NORMOTENSIVE AND HYPERTENSIVE SUBJECTS*
Authors: Ervin A. Gombos, William H. Hulet, Pierre Bopp, William Goldring, David S. Baldwin, Herbert Chasis
Journal: Journal of Clinical Investigation (1962)

Effect of l-norepinephrine on renal and systemic hemodynamics in normotensive and hypertensive subjects on regular salt intake * Subjectt l-Norepineph-Urine Age rine volume GFR RPF FF RR Pm Pulse yrs Aglminl ml/min ml/min ml/min % dynesmm Hg rate/min 1.73 m2 sec-cm' Normotensive subjects M.S.Control 39 4.9 13.2 21.4 42.4 O.V. Control 35 2.6 6.6 12.3 20.0
Management of asthma in hospital: a prospective audit
Authors: C E Bucknall, C Robertson, F Moran, R D Stevenson
Journal: BMJ (1988)

In a prospective study of management of asthma in hospital patients with acute asthma admitted to a single hospital over a calendar year were surveyed. Altogether 157 out of 194 admissions (81%) were studied. The patients (16 of whom had been admitted twice and one three times) were interviewed at home about two weeks after discharge, and their hospital records were reviewed. When interviewed an appreciable proportion of patients said that their asthma had been poorly controlled after their discharge from the hospital: 54 reported regular sleep disturbance due to wheeze, 78 tightness of the chest in the morning, and 77 wheeze after climbing one flight of stairs. Patients had been described on admission as having had symptoms of deteriorating asthma for a median of three days. Closer questioning of 71 patients, however, elicited that 50 had had regular symptoms indicating poor control for weeks or months. Most patients did not know how their drugs worked, and many did not have an appropriate plan of action in the event of a further attack. In all the cases studied 114 patients were treated with oral corticosteroids, only 70 had had their previous maintenance treatment increased at the time of discharge, and 107 had a follow up appointment booked for an average of three and a half weeks after discharge. These findings show that undersupervision and undertreatment of patients with asthma are common and not confined to those dying of the condition.
You are about to see pictorial representations!
Authors: Frédéric Gosselin, Philippe G. Schyns
Journal: Behavioral and Brain Sciences (2002)

Pylyshyn argues against representations with pictorial properties that would be superimposed on a scene. We present evidence against this view, and a new method to depict pictorial properties. We propose a continuum between the top-down generation of internal signals (imagery) and the bottom-up signals from the outside world. Along the continuum, superstitious perceptions provide a method to tackle representational issues.
Completeness of registration of childhood leukaemia near nuclear installations and elsewhere in the Oxford region.
Authors: G. J. Draper, B. D. Bower, S. C. Darby, R. Doll
Journal: BMJ (1989)

From our small series of patients measuring the C reactive protein concentration seems to provide a highly sensitive and inexpensive screening test which is simple and quick to perform.A normal result in our study excluded a deep venous thrombosis.We are grateful to Mr A Hughes of the department. of community health, University of Bristol, for statistical advice and to the Bristol and Weston Health Authority for providing funds for the thermography unit.
SPONTANEOUS CONVULSIONS FOLLOWING CONVULSIVE SHOCK THERAPY
Authors: BERNARD L. PACELLA, S. EUGENE BARRERA
Journal: American Journal of Psychiatry (1945)

1. Of over 500 patients who received electric convulsive therapy, 2 exhibited spontaneous generalized convulsions 6½ to 8 weeks after termination of treatment. These 2 patients had never had seizures prior to treatment, nor were there any epileptic manifestations in any of the family members. 2. Pre-treatment EEGs are reported for the first time in patients exhibiting spontaneous convulsions subsequent to therapy. In both instances, the brain-wave tracings were abnormal prior to shock. 3. It is concluded that spontaneous convulsions following convulsive therapy are prone to occur only in those patients who have latent convulsive tendencies as revealed by the EEG. 4. The suggestion is made that pre-shock EEGs are particularly indicated in patients who give histories of previous convulsions in childhood or later life, or who have family members exhibiting epileptic manifestations.
Pacemaking in Cardiac Infarction
Authors: B. W. Lassers, D. G. Julian
Journal: BMJ (1967)

Members of a local appeal committee have also given of their time working voluntarily in this unit and in L.H.A. clinics.One point does need to be made where this type of project is concerned.As your corre- spondent points out, the maintenance of any unit must be borne by the regional hospital board however the capital is provided.These running costs may run into many thousands of pounds per year.The board has to satisfy itself in each case that it is a reasonable expenditure as some other part of the service may have to suffer in order to make this money available.Dr. Hanna and his colleagues in Gloucestershire were clearly successful in getting a change of plan for radiotherapy units agreed by the Ministry of Health.Finally, we have shown here in Orpington on a smaller scale that whatever political party is in power there will never be sufficient money from Exchequer funds to provide the buildings and equipment that modern medicine requires.It is for this reason, as well, that there will always be a need for the self-help campaigns such as you have described.-I am, etc.,
Excretion of platelet activating factor–acetylhydrolase and phospholipase A2 into nasal fluids after allergenic challenge: Possible role in the regulation of platelet activating factor release
Authors: Lhousseine Touqui, Nathalie Herpin-Richard, Rosa-Maria Gene, Eric Jullian, Dehlia Aljabi, Christine Hamberger, B.Boris Vargaftig, Jean-François Dessange
Journal: Journal of Allergy and Clinical Immunology (1994)
Effect of Short Pulsed Nonablative Infrared Laser Irradiation on Vascular Cells In Vitro and Neointimal Hyperplasia in a Rabbit Balloon Injury Model
Authors: Nicholas Kipshidze, Victor Nikolaychik, Michael Muckerheidi, Michael H. Keelan, Valeri Chekanov, Michelle Maternowski, Paramjit Chawla, Irina Hernandez, Sriram Iyer, George Dangas, Harry Sahota, Martin B. Leon, Gary Roubin, Jeffrey W. Moses
Journal: Circulation (2001)

Background Neointimal hyperplasia after PTCA is an important component of restenosis. Methods and Results Cultures of rabbit endothelial cells and smooth muscle cells (SMCs) were irradiated with different doses of nonablative infrared (1064-nm) radiation. Normalized viability index detected with nondestructive Alamar Blue assay and direct cell count were studied. Our experiments demonstrated dose-dependent cytostatic or cytotoxic effects of laser irradiation. We also evaluated the long-term effect of endoluminal nonablative infrared laser irradiation on neointimal hyperplasia in a rabbit balloon injury model. PTCA of both iliac arteries of 23 New Zealand White rabbits was performed. One iliac artery was subjected to intra-arterial subablative infrared irradiation via a diffuse tip fiber. The contralateral vessel served as control. The diet was supplemented with 0.25% cholesterol and 2% peanut oil for 10 days before and 60 days after PTCA. Morphometry after 60 days showed that intimal areas were 0.76±0.18 and 1.85±0.30 mm 2 in the laser and control arteries, respectively ( P =2.2×10 −11 ). Conclusions We conclude that nonablative infrared laser inhibited neointimal hyperplasia after PTCA in cholesterol-fed rabbits for up to 60 days.
Prevalence and correlates of aortic regurgitation in american indians: the Strong Heart Study
Authors: Nathaniel E Lebowitz, Jonathan N Bella, Mary J Roman, Jennifer E Liu, Dawn P Fishman, Mary Paranicas, Elisa T Lee, Richard R Fabsitz, Thomas K Welty, Barbara V Howard, Richard B Devereux
Journal: Journal of the American College of Cardiology (2000)
Rofecoxib may cause heart attacks in first weeks of use
Authors: Janice Hopkins Tanne
Journal: BMJ (2006)

A small but significant number of elderly people who began taking rofecoxib (Vioxx) had heart attacks in the first two weeks, a study has found. Previously the risk was thought to occur only after 18 months of treatment.

The study was posted online ahead of publication on 2 May by the CMAJ , the journal of the Canadian Medical Association (http://www.cmaj.ca/, doi: 10.1503/cmaj.051 679).

“A small proportion of patients using rofecoxib for the first time had their first MI [myocardial infarction] shortly after starting the drug,” the paper says. The risk was highest in the first six to 13 days (median nine days) after they started treatment with the drug. The risk did not increase …
Diagnostic Acumen of the G.P
Authors: W. Edwards
Journal: BMJ (1946)

<h3>ABSTRACT</h3> Traditional screening for COVID-19 typically includes survey questions about symptoms, travel history, and sometimes temperature measurements. We explored whether longitudinal, personal sensor data can help identify subtle changes which may indicate an infection, such as COVID-19. To do this we developed an app that collects smartwatch and activity tracker data, as well as self-reported symptoms and diagnostic testing results from participants living in the US. We assessed whether symptoms and sensor data could differentiate COVID-19 positive versus negative cases in symptomatic individuals. Between March 25 and June 7, 2020, we enrolled 30,529 participants, of whom 3,811 reported symptoms, 54 reported testing positive for COVID-19, and 279 negative. We found that a combination of symptom and sensor data resulted in an AUC=0.80 [0.73 – 0.86] which was significantly better (p &lt; 0.01) than a model which just considered symptoms alone (AUC=0.71 [0.63 – 0.79]) in the discrimination between symptomatic individuals positive or negative for COVID-19. Such orthogonal, continuous, passively captured data may be complementary to virus testing that is generally a one-off, or infrequent, sampling assay.
Phase II Study of Gemcitabine, Carboplatin, and Bevacizumab in Patients With Advanced Unresectable or Metastatic Urothelial Cancer
Authors: Arjun V. Balar, Andrea B. Apolo, Irina Ostrovnaya, Svetlana Mironov, Alexia Iasonos, Alisa Trout, Ashley M. Regazzi, Ilana R. Garcia-Grossman, David J. Gallagher, Matthew I. Milowsky, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2013)

Purpose Although gemcitabine and carboplatin (GCa) is a standard option for patients with advanced urothelial cancer (UC) who are ineligible for cisplatin, outcomes remain poor. This trial evaluated the efficacy and safety of bevacizumab with GCa in advanced UC. Patients and Methods Patients with Karnofsky performance status of 60% to 70%, creatinine clearance less than 60 mL/min, visceral metastasis, or solitary kidney were eligible and received a lead-in dose of bevacizumab 10 mg/kg followed 2 weeks later by gemcitabine 1,000 mg/m 2 on days 1 and 8 and carboplatin at area under the [concentration-time] curve (AUC) 5.0 or 4.5 and bevacizumab 15 mg/kg on day 1 every 21 days for six cycles. Patients achieving at least stable disease (SD) continued bevacizumab 15 mg/kg every 21 days for 18 additional cycles. The study was powered to detect a 50% improvement in median progression-free survival (PFS) over a historical control. Results Fifty-one patients, median age 67 years (range, 42 to 83 years), were enrolled onto the study and were evaluable for toxicity. Twenty (39%) experienced grade 3 to 4 toxicity, and 10 (20%) had thromboembolic events (deep venous thrombosis or pulmonary embolism). Four received one or fewer cycles leaving 47 evaluable for outcomes. Twenty-three (49%) achieved response (three complete; 20 partial), and 11 had SD. Median PFS was 6.5 months (95% CI, 4.7 to 7.8 months); PFS was greater in the carboplatin AUC 5.0 group (P = .04). Median overall survival (OS) was 13.9 months. Conclusion The 95% one-sided lower confidence bound of 4.77 months for median PFS did not meet the predesignated PFS of more than 4.8 months considered sufficient for further study. Median OS was greater than expected. An ongoing phase III trial in patients who are eligible for therapy with cisplatin will define the role of bevacizumab in UC.
Abstract 2880: Spices suppress oxidative stress during DMBA induced skin carcinogenesis in mice, mimicking human non-melanoma skin cancer
Authors: Ila Das, Asha Acharya, Archana Sengupta, Shukta Das, Sudin Bhattacharya, Tapas Saha
Journal: Cancer Research (2010)

Abstract Background: Cancer chemoprevention is the use of natural, synthetic or biologic substances to reverse, suppress, or prevent the development of cancer. Spices like cinnamon, cardamom and cumin are the naturally occurring phytoproducts that display an active cancer preventive strategy to inhibit, delay or reverse the human carcinogenesis. Aims and Objectives: Our aim of this study is to decipher the chemopreventive effect of aqueous infusion of the spices as a diet on DMBA induced skin carcinogenesis, which mimics UV radiation mediated non melanoma skin cancer that has high mortality rate if not diagnosed early. Research Design and Methodology: Female Swiss Albino Mice have been divided into 5 groups in each case. Normal control (NC) and DMBA treated control (CC) mice received acetone and DMBA/croton oil on it's dorsally shaven skin for eight weeks, respectively. Aqueous suspensions of the spices were orally administered to three groups of mice either before or after or both before and after DMBA applications on the shaved skin during the entire study period. Treated skins were excised after harvesting the mice and H &amp; E staining, immunohistochemistry assays for lipid peroxides, antioxidation enzymes activities, immunoblotting, cell proliferation and apoptosis were performed. Results: All the spices demonstrate inhibition of the skin papillomagenesis. The best chemopreventive actions of these spices were observed when the spice treatments were performed both before and after the induction of skin carcinogenesis by DMBA. An up-regulation of the phase II detoxification enzymes and induction of non-protein thiol antioxidants were observed in mice treated with the spices. Additionally, cumin and cardamom demonstrate downregulation of COX-2 expression, inhibit cell proliferation and block p53-induced apoptosis. Cardamom stimulates NRF2 and inhibits NF-κB transcription factors to demonstrate its beneficial action against skin carcinogenesis. Conclusion: Spices inhibit DMBA induced skin carcinoma in mice when treated early and it is believed to be due, at least in part, to the induction of cellular defense systems. We are in a process of identifying unique chemical components of these spices to maximize the benefits. References: 1. Das, I., and Saha, T.; Nutrition. (2009); 25(4):459-471. 2. Das, I., Das, S. and Saha, T.; Acta Histochem. (2009); (In Press) 3. Das, I., Rana, T., Sengupta, A., and Saha, T.; J. Biol. Chem. 2009; (In Revision) 4. Acharya, A, Das, I., Chandhok, D., and Saha, T.; Oxidative Stress and Cellular Longevity; 2009; (In Press) 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 2880.
Cell-Type-Specific Expression of STAT Transcription Factors in Tissue Samples from Patients with Lymphocytic Thyroiditis
Authors: Julia Staab, Peter J. Barth, Thomas Meyer
Journal: Endocrine Pathology (2012)

Expression of cytokine-regulated signal transducer and activator of transcription (STAT) proteins was histochemically assessed in patients diagnosed as having Hashimoto's disease or focal lymphocytic thyroiditis (n = 10). All surgical specimens showed histological features of lymphocytic thyroiditis, including a diffuse infiltration with mononuclear cells and an incomplete loss of thyroid follicles, resulting in the destruction of glandular tissue architecture. Immunohistochemical analysis demonstrated differential expression patterns of the various members of the STAT transcription factors examined, indicating that each member of this conserved protein family has its distinct functions in the development of the disease. Using an antibody that specifically recognized the phosphorylated tyrosine residue in position 701, we detected activated STAT1 dimers in numerous germinal macrophages and infiltrating lymphocytes as well as in oncocytes. In contrast, STAT3 expression was restricted to epithelial cells and showed a clear colocalization with the antiapoptotic protein Bcl-2. Moreover, expression of phospho-STAT3 was associated with low levels of stromal fibrosis, suggesting that STAT3 serves as a protective factor in the remodeling of the inflamed thyroid gland. Phospho-STAT5 immunoreactivity was detected in numerous infiltrating cells of hematopoietic origin and, additionally, in hyperplastic follicular epithelia. This tissue distribution demonstrated that activated STAT5 molecules participate in both lymphocytopoiesis and possibly also in the buildup of regenerating thyroid follicles. Taken together, the cell-type-specific expression patterns of STAT proteins in human lymphocytic thyroiditis reflect their distinct and partially antagonistic roles in orchestrating the balance between degenerating and regenerating processes within a changing cytokine environment.
Muscle Function and Resting Energy Expenditure in Female Athletes with Cystic Fibrosis
Authors: Hiran C. Selvadurai, Jane Allen, Toos Sachinwalla, James Macauley, Cameron J. Blimkie, Peter P. Van Asperen
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The pathophysiology of impaired exercise tolerance in patients with cystic fibrosis (CF) is not completely understood. The objective of this study was to compare exercise ability (at clinical and cellular levels) and resting energy expenditure in female athletes with CF compared with matched control subjects. Sixteen subjects and matched control subjects participated in the study. The girls with CF not only had a significantly greater resting energy expenditure (7.6% higher; p<0.05), their habitual daily activity was also significantly greater than that of control subjects (15% greater; p<0.01). Peak aerobic capacity was similar in both groups. However, peak anaerobic power was 20% less (p<0.05) in girls with CF. The 31P magnetic resonance spectroscopy studies demonstrated that there were no differences between the groups at rest, but at 25% total work output the girls with CF were less acidotic (CF, pH 6.99 [0.06]; control subjects, 6.90 [0.05]) and had a significantly lower inorganic phosphorus-to-phosphocreatine ratio (CF, 0.34 [0.07]; control subjects, 0.41 [0.08]). These differences continued to increase to maximal exercise. This study demonstrates that in spite of normal lung function and good nutritional status, females athletes with CF still had significant deficiencies in some measures of fitness and muscle metabolism compared with healthy athletes.
Science, medicine, and the future: Antivascular therapy: a new approach to cancer treatment
Authors: A J Hayes, L Y Li, M E Lippman
Journal: BMJ (1999)

The understanding that the growth of tumours is dependent on angiogenesis has led to the development of new approaches to treatment and new agents directed at tumour vasculature. These have yielded striking successes in experimental models, which if translated into the clinical setting will have a substantial effect on patient survival. Such new approaches are vital because, although great strides have occurred in the treatment of certain cancers, the overall standardised mortality from most solid tumours has altered little over the past two decades.1

This article considers the process of tumour angiogenesis and discusses the potential of angiogenic inhibitors as therapeutic agents.



Role of angiogenesis in growth of tumours



The vascularity of tumours has been noted for many years.2 Alguire noted that vascularisation was instigated by the developing tumour: “An outstanding characteristic of the growing tumour is its capacity to elicit the production of a new capillary endothelium from the host.”3 Tannock elegantly showed that the rate of division of tumour cells decreased in proportion to their distance from the supplying blood vessel and related this to diminishing oxygen supply.4 Moreover, he showed that the overall rate of growth was dictated not by proliferation of tumour cells but by the lower rate of proliferation of endothelial cells, concluding that the supply of oxygen and nutrients to the tumour limited its growth.

#### Predicted developments

Tumour …
Death rate from ovarian cancer in England has fallen by a fifth since 2001
Authors: Z. Kmietowicz
Journal: BMJ (2012)

The mortality rate from ovarian cancer in England fell from 11.2 women in every 100 000 (3820 cases) in 2001 to 8.8 per 100 000 (3453 cases) in 2010—a drop of about 20%, show latest figures.1

One year survival after diagnosis of ovarian cancer increased from 57% in the mid-1980s to 73% in 2010, and five year survival increased from 33% to 44%, says a report from the National Cancer Intelligence Network.

The most notable drop in deaths over the past 10 years has been among women aged 40-69 years. …