tbuckley/cabot-search huggingface dataset:
Toxigenic <i>Helicobacter pylori</i> Infection Precedes Gastric Hypochlorhydria in Cancer Relatives, and <i>H. pylori</i> Virulence Evolves in These Families
Authors: Richard H. Argent, Rachael J. Thomas, Francisco Aviles-Jimenez, Darren P. Letley, Marie C. Limb, Emad M. El-Omar, John C. Atherton
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Helicobacter pylori infection by virulent strains is associated with gastric adenocarcinoma. We aimed to determine whether infection with virulent H. pylori preceeded precancerous gastric hypochlorhydria and atrophy in gastric cancer relatives and quantify the extent of virulence factor evolution. Experimental Design: H. pylori strains from 51 Scottish gastric cancer relatives were characterized by genetic fingerprinting and typing the vacuolating cytotoxin gene (vacA), the cytotoxin-associated gene (cagA), and housekeeping genes. We phenotyped strains by coculture with gastric epithelial cells and assessing vacuolation (microscopy), CagA tyrosine phosphorylation (immunoblot), and interleukin-8 secretion (ELISA). Results: Toxigenic (vacA type s1/m1) H. pylori was associated with precancerous gastric hypochlorhydria (P &amp;lt; 0.01). Adult family members with this type of H. pylori had the same strain as currently noncohabiting adult family members in 68% cases, implying acquisition during childhood from each other or a common source. We analyzed different isolates of the same strain within families and showed that H. pylori commonly microevolved to change virulence: this occurred in 22% individuals and a striking 44% cases where the strain was shared within families. Microevolution in vacA occurred by extragenomic recombination and in cagA by this or duplication/deletion. Microevolution led to phenotypic changes in virulence. Passage of microevolved strains could be tracked within families. Conclusions: Toxigenic H. pylori infection precedes and so likely causes gastric hypochlorhydria, suggesting that virulent H. pylori increases cancer risk by causing this condition. Microevolution of virulence genes is common within families of gastric cancer patients and changes H. pylori virulence.
Realising the potential for an Olympic legacy; teaching medical students about sport and exercise medicine and exercise prescribing
Authors: Paul R Jones, John H M Brooks, Ann Wylie
Journal: British Journal of Sports Medicine (2013)

Background Physicians are increasingly being called upon to promote physical activity (PA) among patients. However, a paucity of exercise medicine teaching in the UK undergraduate medical curricula prevents students from acquiring the necessary knowledge and skills to do so. To address this issue, King's College London School of Medicine introduced an exercise medicine strand of teaching. This study evaluated the acceptability of exercise promotion behaviour change lectures and explored the knowledge and attitudes of the students who received it. Methods Students were invited to complete a 6-item online questionnaire prior to and after exercise medicine lectures. The questionnaire assessed beliefs regarding the importance of PA in disease prevention and management, in addition to their confidence in advising patients on PA recommendations. A focus group (n=7) explored students’ attitudes towards and knowledge of PA promotion and exercise prescribing. Results In total, 121 (15%) first-year and second-year MBBS students completed the questionnaire. Students’ beliefs regarding the importance of PA in managing disease and their confidence in PA promotion among patients increased after the teaching (p&lt;0.001). More students were able to correctly identify the Chief Medical Officer recommended adult PA guidelines (p&lt;0.05). Students were enthusiastic about the exercise medicine teaching, strongly supportive of its continued inclusion in the curriculum and advocated its importance for patients and themselves as future doctors. Conclusions Behaviour change teaching successfully improved students’ knowledge of and confidence regarding PA promotion. These improvements are a step forward and may increase the rates and success of physician PA counselling in the future.
Role of angiotensin II and potassium in the long-term regulation of aldosterone secretion in intact conscious dogs.
Authors: R E McCaa, C S McCaa, A C Guyton
Journal: Circulation Research (1975)

The aldosterone response to long-term infusion of angiotensin II and potassium was studied in intact conscious dogs. Plasma aldosterone concentration (PAC), plasma renin activity (PRA), and plasma cortisol concentration (PCC) were determined by radioimmunoassay. In ten dogs maintained on angiotension II infusion (5 ng/kg min-1) for 14 days, PAC increased from 6.9 plus or minus 2.9 to 18.6 plus or minus 4.7 ng/100 ml plasma (mean plus or minus SE) within ten minutes after beginning the infusion, reached a maximum level of 28.3 plus or minus 6.8 ng/100 ml plasma by one hour, and returned to control levels by six hours. PCC increased from 0.6 plus or minus 0.2 to 3.9 plus or minus 1.0 mu-g/ 100 ml plasma within one hour after angiotensin II infusion and returned to control levels by six hours. During the next 14 days of angiotensin infusion, PAC remained at control levels, PRA was undetectable by radioimmunoassay, and mean arterial blood pressure was elevated 29 plus or minus 4 mm Hg above control levels. In ten dogs maintained on KCL infusion (250 mEg/day) for 15 days, PAC increased from 6.8 plus or minus 2.4 to 13.6 plus or minus 3.4 ng/100 ml plasma within 24 hours, averaged 22.4 plus or minus 4.3 ng/100 ml plasma by 48 hours, and remained elevated for the next 12 days, averaging 21.8 plus or minus 5.6 ng/100 ml plasma. During the next 14 days of KCL infusion, serum Kn increased from 4.1 plus or minus 0.3 to 4.9 plus or minus 0.5 ME1/L, and PRA decreased from 1.25 plus or minus 0.3 to 0.65 plus or minus 0.2 ng/ml/hr. PCC averaged 0.73 plus or minus 0.4 mu-g/100 ml plasma in the control samples and failed to change significantly during KCL infusion. These data indicate that chronic angiotensin II infusion into intact conscious dogs at rates capable of maintaining elevated arterial blood pressure results in a transient increase in aldosterone secretion that lasts only a few hours, while chronic infusion of potassium ions at rates that produce a minor increase in serum Kn results in a sustained increase in aldosterone secretion.
Women with Left Frontal Glioblastoma Have a Significantly Shorter Survival—Why?
Authors: Leif G. Salford, Erik Nordenström, Gunnar Skagerberg, Torgil Möller, Bengt Widegren, Roland Perfekt
Journal: Neuro-Oncology (2006)

Women with Left Frontal Glioblastoma Have a Significantly Shorter Survival -Why?A new retrospective study of 369 patients with distinct lobar GBM localization, conducted in our department from 1988 to 1997, shows the same results: 26 women with left-sided frontal tumors have a shorter survival time (P 5 0.002; log-rank test) than 21 women with right-sided frontal tumors.When all women studied from 1981 to 1997 are included, 37 with left-sided frontal GBMs have a shorter survival time than 32 with rightsided frontal tumors (P 5 0.0001; log-rank test).How can this be explained?Is an immunostimulating center in the left frontal lobe destroyed by the infiltrating tumor?Why only in women?Hormonal influence?Leftsided GBMs in men do not kill faster than right-sided GBMs, and surgical extensiveness is not related to sex.The literature describes many unexplained differences between the hemispheres and genders in function and in hormonal, transmitter, and immunological situations.However, brain injury has proven to induce immune deficiency syndrome (Meisel et al., 2005), and if studied in detail, the localization of the injury and gender might stratify these effects further.Continued search for these and other differences may give clues to a better understanding of the battle between the advancing malignant brain tumor and its hosting brain, and thereby possibilities for improved therapies.
Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis
Authors: Christoph Kleinschnitz, Guido Stoll, Martin Bendszus, Kai Schuh, Hans-Ulrich Pauer, Peter Burfeind, Christoph Renné, David Gailani, Bernhard Nieswandt, Thomas Renné
Journal: The Journal of Experimental Medicine (2006)

Formation of fibrin is critical for limiting blood loss at a site of blood vessel injury (hemostasis), but may also contribute to vascular thrombosis. Hereditary deficiency of factor XII (FXII), the protease that triggers the intrinsic pathway of coagulation in vitro, is not associated with spontaneous or excessive injury-related bleeding, indicating FXII is not required for hemostasis. We demonstrate that deficiency or inhibition of FXII protects mice from ischemic brain injury. After transient middle cerebral artery occlusion, the volume of infarcted brain in FXII-deficient and FXII inhibitor–treated mice was substantially less than in wild-type controls, without an increase in infarct-associated hemorrhage. Targeting FXII reduced fibrin formation in ischemic vessels, and reconstitution of FXII-deficient mice with human FXII restored fibrin deposition. Mice deficient in the FXII substrate factor XI were similarly protected from vessel-occluding fibrin formation, suggesting that FXII contributes to pathologic clotting through the intrinsic pathway. These data demonstrate that some processes involved in pathologic thrombus formation are distinct from those required for normal hemostasis. As FXII appears to be instrumental in pathologic fibrin formation but dispensable for hemostasis, FXII inhibition may offer a selective and safe strategy for preventing stroke and other thromboembolic diseases.
The demand for ophthalmic services.
Authors: A. R. Rosenthal
Journal: BMJ (1992)

mates the scale of the problem in Britain.Ochronosis is often an incidental finding, and patients may not realise that their gradual facial darkening is a side effect of the cream that was intended to lighten their skin.Some continue to apply more cream as they get caught in the "skin lightener trap."Many patients may also feel guilty about using such creams and will often deny their use-even when histological evidence of ochronosis is available.Although more public awareness of the dangers of skin lighteners may reduce their use, sufficient doubt exists regarding the safety of creams containing 2% hydroquinone to justify a temporary ban on over the counter use pending long term trials of their safety.The onus should be on manufac- turers rather than consumers to establish such safety.Had it been a drug and not a cosmetic the product licence would have probably long been withdrawn.
High-efficiency RNA cloning enables accurate quantification of miRNA expression by deep sequencing
Authors: Zhaojie Zhang, Jerome E Lee, Kent Riemondy, Emily M Anderson, Rui Yi
Journal: Genome biology (2013)

Small RNA cloning and sequencing is uniquely positioned as a genome-wide approach to quantify miRNAs with single-nucleotide resolution. However, significant biases introduced by RNA ligation in current protocols lead to inaccurate miRNA quantification by 1000-fold. Here we report an RNA cloning method that achieves over 95% efficiency for both 5′ and 3′ ligations. It achieves accurate quantification of synthetic miRNAs with less than two-fold deviation from the anticipated value and over a dynamic range of four orders of magnitude. Taken together, this high-efficiency RNA cloning method permits accurate genome-wide miRNA profiling from total RNAs.
Vascular Endothelial Growth Factor Signaling Pathways: Therapeutic Perspective
Authors: Marcin Kowanetz, Napoleone Ferrara
Journal: Clinical Cancer Research (2006)

Abstract The establishment of a vascular supply is one of the earliest and most important events occurring during embryonic development. Growth and maturation of a functional vascular network are complex and still incompletely understood processes involving orchestrated activation of vascular progenitors in the early stages of embryonic development followed by vasculogenesis and angiogenesis. These processes require a tightly regulated activation of several growth factors and their receptors. The role of vascular endothelial growth factors (VEGF) and their receptors has been studied extensively due to their prominent role during blood vessel formation. Mice deficient in various VEGF ligands or receptors show serious defects in vascular formation and maturation. Moreover, members of the VEGF family are involved in other significant biological processes, including lymphangiogenesis, vascular permeability, and hematopoiesis. Importantly, VEGF is released by tumor cells and induces tumor neovascularization. It is now well established that the VEGF axis represents an important target for antitumor therapy. Aberrant VEGF signaling is also a feature of several other pathologic conditions, such as age-related macular degeneration and rheumatoid arthritis.
The sodium channel-blocking antiepileptic drug phenytoin inhibits breast tumour growth and metastasis
Authors: Michaela Nelson, Ming Yang, Adam A Dowle, Jerry R Thomas, William J Brackenbury
Journal: Molecular Cancer (2015)

Voltage-gated Na(+) channels (VGSCs) are heteromeric protein complexes containing pore-forming α subunits and smaller, non-pore-forming β subunits. VGSCs are classically expressed in electrically excitable cells, e.g. neurons. VGSCs are also expressed in tumour cells, including breast cancer (BCa) cells, where they enhance cellular migration and invasion. However, despite extensive work defining in detail the molecular mechanisms underlying the expression of VGSCs and their pro-invasive role in cancer cells, there has been a notable lack of clinically relevant in vivo data exploring their value as potential therapeutic targets.We have previously reported that the VGSC-blocking antiepileptic drug phenytoin inhibits the migration and invasion of metastatic MDA-MB-231 cells in vitro. The purpose of the present study was to establish whether VGSCs might be viable therapeutic targets by testing the effect of phenytoin on tumour growth and metastasis in vivo. We found that expression of Nav1.5, previously detected in MDA-MB-231 cells in vitro, was retained on cells in orthotopic xenografts. Treatment with phenytoin, at a dose equivalent to that used to treat epilepsy (60 mg/kg; daily), significantly reduced tumour growth, without affecting animal weight. Phenytoin also reduced cancer cell proliferation in vivo and invasion into surrounding mammary tissue. Finally, phenytoin significantly reduced metastasis to the liver, lungs and spleen.This is the first study showing that phenytoin reduces breast tumour growth and metastasis in vivo. We propose that pharmacologically targeting VGSCs, by repurposing antiepileptic or antiarrhythmic drugs, should be further studied as a potentially novel anti-cancer therapy.
Detecting severe silent mitral regurgitation.
Authors: S. Thorne, T. Richens, P. Mills
Journal: BMJ (1992)

I have knowledge of 50 deaths (this includes unpublished cases from personal communica- tions).The problem is sporadic and rare; because the consequences are so devastating for the patient, however, the medical and nursing staff managing patients with central venous catheters must prevent air gaining access to the venous circulation.4"
Relationship Between Leg Length and Gestational Diabetes Mellitus in Chinese Pregnant Women
Authors: Run Mei Ma, Terence T. Lao, Chun Ling Ma, Shu Jie Liao, Yan Feng Lu, Ming Yu Du, Hong Xiao, Lan Zhang, Ming Hui Yang, Xue Xiao
Journal: Diabetes Care (2007)

The relationship between maternal short stature and gestational diabetes mellitus (GDM) remains controversial. While such an association has been shown in Europeans, South Americans, and Southern Asians (1–5), it was not demonstrated in Hungarians of European origin (6). Apart from ethnic differences, the contribution of the different components of height to overall height could have influenced this association, since leg length rather than trunk length has been correlated with type 2 diabetes in British women (7), and a similar observation in women with GDM has since been reported (5). As Chinese women are generally shorter than their European counterparts because of shorter legs, we have examined the relationship between overall height and components of height with the development of GDM in Chinese women to address this issue.

This prospective cohort study was conducted in Kunming, China, from August 2004 to March 2005. All the patients were ethnic Chinese. A 75-g oral glucose tolerance test (OGTT) was arranged at booking for women with risk factors for GDM. If the initial results were normal, the OGTT was repeated at 28–32 weeks. All low-risk women received the OGTT at 28–32 weeks. No preliminary challenge test was used. The OGTT results were interpreted by World Health Organization criteria (8), which have been studied in Chinese populations before (9–11 …
Induction chemotherapy and concurrent chemoradiotherapy for locoregionally advanced head and neck cancer: a multi-institutional phase II trial investigating three radiotherapy dose levels
Authors: J.K. Salama, K.M. Stenson, E.O. Kistner, B.B. Mittal, A. Argiris, M.E. Witt, F. Rosen, B.E. Brockstein, E.E.W. Cohen, D.J. Haraf, E.E. Vokes
Journal: Annals of Oncology (2008)
Inhibition of Myosin Phosphatase by Upregulated Rho-Kinase Plays a Key Role for Coronary Artery Spasm in a Porcine Model With Interleukin-1β
Authors: Tadashi Kandabashi, Hiroaki Shimokawa, Kenji Miyata, Ikuko Kunihiro, Yoji Kawano, Yuko Fukata, Taiki Higo, Kensuke Egashira, Shosuke Takahashi, Kozo Kaibuchi, Akira Takeshita
Journal: Circulation (2000)

Background —We recently demonstrated that the Rho-kinase–mediated pathway plays an important role for coronary artery spasm in our porcine model with interleukin-1β (IL-1β). In this study, we examined whether or not Rho-kinase is upregulated at the spastic site and if so, how it induces vascular smooth muscle hypercontraction. Methods and Results —Segments of the left porcine coronary artery were chronically treated from the adventitia with IL-1β–bound microbeads. Two weeks after the operation, as reported previously, intracoronary serotonin repeatedly induced coronary hypercontractions at the IL-1β–treated site both in vivo and in vitro, which were markedly inhibited by Y-27632, one of the specific inhibitors of Rho-kinase. Reverse transcription–polymerase chain reaction analysis demonstrated that the expression of Rho-kinase mRNA was significantly increased in the spastic compared with the control segment. Western blot analysis showed that during the serotonin-induced contractions, the extent of phosphorylation of the myosin-binding subunit of myosin phosphatase (MBS), one of the major substrates of Rho-kinase, was significantly greater in the spastic than in the control segment and that the increase in MBS phosphorylations was also markedly inhibited by Y-27632. There was a highly significant correlation between the extent of MBS phosphorylations and that of contractions. Conclusions —These results indicate that Rho-kinase is upregulated at the spastic site and plays a key role in inducing vascular smooth muscle hypercontraction by inhibiting myosin phosphatase through the phosphorylation of MBS in our porcine model.
England's health secretary orders three new inquiries into safety of cosmetic surgery and devices
Authors: A. O'Dowd
Journal: BMJ (2012)

The UK private surgery firm that carried out the greatest number of implants made by the now discredited and bankrupt French company Poly Implant Prosthese (PIP) has refused to pay for the removal and replacement of the implants, claiming that the fault lies with the government.

The Department of Health for England meanwhile has launched a new inquiry into how to ensure the safety of people seeking cosmetic interventions and insists that it will pursue private companies for payment of operations if those companies refuse to help affected women.

The row over PIP implants has continued this week with an increasingly belligerent exchange of words between the government and the private cosmetic industry—the BMJ understands that 16 major clinics or companies are involved.

Last December the French government announced that it would pay for all 30 000 women in France with PIP implants to have them removed after concerns that they were made with non-medical grade silicone …
Randomized Comparison of Olanzapine Versus Risperidone for the Treatment of First-Episode Schizophrenia: 4-Month Outcomes
Authors: Delbert G Robinson, Margaret G Woerner, Barbara Napolitano, Raman C Patel, Serge M Sevy, Handan Gunduz-Bruce, Jose M Soto-Perello, Alan Mendelowitz, Ali Khadivi, Rachel Miller, Joanne McCormack, Beth S Lorell, Martin L Lesser, Nina R Schooler, John M Kane
Journal: American Journal of Psychiatry (2006)

The authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders.One hundred twelve subjects (70% male; mean age=23.3 years [SD = 5.1]) with first-episode schizophrenia (75%), schizophreniform disorder (17%), or schizoaffective disorder (8%) were randomly assigned to treatment with olanzapine (2.5-20 mg/day) or risperidone (1-6 mg/day).Response rates did not significantly differ between olanzapine (43.7%, 95% CI=28.8%-58.6%) and risperidone (54.3%, 95% CI=39.9%-68.7%). Among those responding to treatment, more subjects in the olanzapine group (40.9%, 95% CI=16.8%-65.0%) than in the risperidone group (18.9%, 95% CI=0%-39.2%) had subsequent ratings not meeting response criteria. Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications. Extrapyramidal symptom severity scores were 1.4 (95% CI=1.2-1.6) with risperidone and 1.2 (95% CI=1.0-1.4) with olanzapine. Significantly more weight gain occurred with olanzapine than with risperidone: the increase in weight at 4 months relative to baseline weight was 17.3% (95% CI=14.2%-20.5%) with olanzapine and 11.3% (95% CI=8.4%-14.3%) with risperidone. Body mass index at baseline and at 4 months was 24.3 (95% CI=22.8-25.7) versus 28.2 (95% CI=26.7-29.7) with olanzapine and 23.9 (95% CI=22.5-25.3) versus 26.7 (95% CI=25.2-28.2) with risperidone.Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine.
Ketotifen inhibits PAF-induced actin polymerization in a human eosinophilic leukaemia cell line, EoL-1
Authors: M Morita, S Tsuruta, KJ Mori, M Mayumi, H Mikawa
Journal: European Respiratory Journal (1990)

The inhibitory effect of ketotifen on platelet activating factor (PAF)-induced actin polymerization in a human eosinophilic leukaemia cell line, EoL-1, was examined by flow cytometry with the use of reagents specific for the filamentous form of actin (F-actin). Actin polymerization has been considered to be essential for locomotion of cells, chemotaxis and chemokinesis, and thus it reflects the chemotactic reaction of EoL-1 cells stimulated by PAF. Unstimulated EoL-1 cells showed little PAF-induced actin polymerization, whereas EoL-1 cells cultured for 9 days with the supernatant of a human ATL cell line, HIL-3 (HIL-3 sup), showed marked actin polymerization when stimulated with PAF. The actin polymerization in EoL-1 cells induced by PAF was seen in a dose-dependent manner at concentrations of 10(-10) M to 10(-6) M of PAF, and the maximum effect was seen at 10(-7) M of PAF. CV-3988, a specific antagonist of PAF, inhibited 80% of the actin polymerization in EoL-1 cells induced by PAF at a concentration of 10(-5) M. Ketotifen inhibited up to 40% of the PAF-induced actin polymerization of EoL-1 cells in a dose-dependent manner at concentrations of 10(-9) M to 10(-5) M. These results suggest that ketotifen may play an important role in the prevention of eosinophil-induced inflammation in allergic disorders by inhibiting PAF-induced chemotaxis of eosinophils.