tbuckley/cabot-search huggingface dataset:
Abstract 4730: The double bromodomain protein Brd2 controls B cell expansion and mitogenesis.
Authors: Anna C. Belkina, Wanda P. Blanton, Frank L. Lombardi, Gerald V. Denis
Journal: Cancer Research (2013)

Abstract Background: Bromodomain-containing coregulators of transcription have been identified recently as new epigenetic targets to treat a variety of hematologic malignancies, including acute myeloid leukemias. However, the bromodomain mechanisms that couple histone acetylation to transcription in lymphopoiesis, and that govern mature lymphocyte responsiveness to growth signals, are only partly understood. Brd2 is a transcriptional co-regulator that contains dual Bromodomains and an ExtraTerminal domain (defining the BET family) that couples chromatin modification to cell cycle progression. We previously reported the first functional characterization of a BET protein as an effector of mammalian mitogenic signal transduction: Eμ-Brd2 transgenic mice develop an ‘activated B cell’ type of diffuse large B cell lymphoma. There have been no other animal models reported for genetic or lentiviral expression of BET proteins, which hampers testing of novel anticancer drugs such as JQ1 and its derivatives. Methods: Here we use Brd2 lentivirus transduction of hematopoietic stem cells and reconstitution of lethally irradiated recipient mice to examine the function of Brd2 in hematopoiesis in the bone marrow and mitogenesis in the periphery. Results: Three-fold over-expression of Brd2 in hematopoietic stem cells selectively leads to a doubling of the B cell compartment and increases mature B cell mitogenic responsiveness ex vivo. Knockdown of Brd2 by shRNA totally ablates hematopoietic lineages, likely by inhibiting the lineage-committed progenitor expansion through down-regulation of cyclin A, which reinforces results from Eμ-Brd2 transgenic mice. The novel small molecule BET inhibitor JQ1 reduces B cell mitogenesis by about 60% in parallel experiments, but this effect likely extends to other related BET family members and lacks Brd2 specificity. Conclusion/Significance: The Brd2 pathway integrates lymphopoiesis, leukemogenesis and normal mitogenesis. Targeting this pathway with therapeutic drugs may therefore confer multiple, diverse benefits in the treatment of hematologic malignancy, B cell mediated disease and likely inflammation. Citation Format: Anna C. Belkina, Wanda P. Blanton, Frank L. Lombardi, Gerald V. Denis. The double bromodomain protein Brd2 controls B cell expansion and mitogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4730. doi:10.1158/1538-7445.AM2013-4730
Barry Winston Lewis
Authors: Harvey Marcovitch, Jake McKinnon, Gerald McEnery
Journal: BMJ (2005)

​ConsultantConsultant paediatrician London (b 1941; q University College Hospital, London, 1965; FRCP, FRCPCH), d 2 June 2004.




Figure 1




Barry became a consultant paediatrician at Whipps Cross Hospital in 1973. He started the neonatal unit and set up a popular MRCP course. Meanwhile, his Wimpole Street practice expanded and he left the NHS in 1984. He was instrumental in bringing together obstetricians and paediatricians practising privately to set up the Portland Hospital for mothers and children. Barry's portrait is engraved on a plaque in the hospital's foyer. His last decade was dogged by ill health, but this did not stop his ebullience and enthusiasm. He leaves a wife, Jo; three children; and four grandchildren.
Transcapillary Exchange En the Working Left Ventricle of the Dog
Authors: Wilfred H. Ziegler, Carl A. Goresky
Journal: Circulation Research (1971)

Sets of multiple indicator dilution curves were obtained from working hearts of dogs with closed chests. A multiple capillary adaptation of a permeability-limited capillary model which assumes that exchanging material returns to the capillary at its site of escape was tested on these curves. The model has only two lumped parameters: a permeability surface product per accessible extravascular volume, and flow per extravascular volume. Labeled red cells and albumin were used as vascular indicators. The model provided close fits for the curves of diffusion-limited indicators (sucrose, inulin, sulfate, sodium, chloride, and urea), and unique values were obtained for both parameters. The accessible extravascular volume obtained by this method was independent of flow whereas the permeability surface product per accessible extravascular volume (a relatively low value for these indicators) increased with flow. In this first group the outflow patterns varied with the size of the test molecule. For a second group of substances (water, ethanol and antipyrine), the outflow patterns were virtually identical and independent of molecular size (i.e., flow-limited). The modeling did not provide an appropriate description of these curves, and analysis indicated that the exchanging indicator may intercommunicate between capillaries in a random fashion, i.e., that the indicator may not return to each capillary at the same site at which it escaped.
Government should outlaw theft of DNA, commission says
Authors: Z. Kmietowicz
Journal: BMJ (2002)

Taking people's DNA without their knowing should be a criminal offence, says the United Kingdom's genetics watchdog.

The advice to outlaw DNA theft is just one of a series of recommendations made by the Human Genetics Commission this week to protect personal genetic information from being misused—whether by research institutes, the police, employers, journalists, or family members who may have their own reasons for carrying out genetic tests without a person's consent.

Altogether four new laws may need to be created to protect the public from inappropriate use of their …
Cholera Vaccines and the El Tor Vibrio
Authors: E. E. Vella
Journal: BMJ (1963)

Cholera is an acute infectious disease caused by a Gram- negative comma-shaped organism, the Vibrio cholerae, of which three subtypes are usually described-namely, the Inaba, the Ogawa, and the Hikojima.These three types share common 0 antigens, and hence these organisms may be regarded as representing 0 forms of a single serotype (Wilson and Miles, 1955).Another vibrio organism, the El Tor vibrio, is also capable of causing a cholera-like infection, and the resulting disease has been called paracholera.Epidemio- logically, the El Tor vibrio causes sporadic cases, but though the morbidity may be low the mortality may be high.This vibrio shares "H " and "0 " antigens in common with the true cholera vibrios; it can, however, be differentiated from the latter vibrios by various tests -for example, haemolysis of sheep's red blood corpuscles, a positive Voges-Proskauer reaction, and resistance to cholera bacteriophages.A widespread paracholera epidemic, caused by an El Tor vibrio, was reported in 1961 from diverse countries in the Far East, including the British colony of Hong Kong.Considerable quantities of cholera vaccine, prepared in the David Bruce Laboratories, were despatched at the request of the Far Eastern Land
Fundamentals of Cardiopulmonary Resuscitation
Authors: Valentino D. B. Mazzia
Journal: JAMA (1966)

<i>Fundamentals of Cardiopulmonary Resuscitation</i>is a basic manual of current methods written by a surgeon and an anesthesiologist who are pre-eminent in the field. The book is an excellent training monograph, presenting in 14 well-written chapters the anatomical, physical, and physiological basis of modern resuscitative techniques. The recognition of cardiopulmonary arrest, the fundamentals of airway management, drug therapy, and post-resuscitative care are discussed. The chapter on the organization and training of resuscitative teams will be particularly helpful to hospital administrators. In spite of its overall excellence, several omissions bear comment. The authors do not discuss the absence of the pupillary response to light in cardiac arrest, the problem of when to perform a thoracotomy, the use of succinylcholine as an emergency drug, or the unique problems in resuscitation of the newborn. A list of available resuscitative equipment and a discussion of the logistic problems in times of catastrophe would be
Secondary Prevention after Ischemic Stroke
Authors: Haifeng Zhang, Franz H Messerli, Jan A Staessen
Journal: New England Journal of Medicine (2012)

placebo has yet been published.Furthermore, patients with "confirmed persistent disease" (which was determined only after the administration of iodine-131) were removed from the final study analysis.This is notable when one considers how best to design a placebo-based investigation, since such patients may not have been identified without the radioiodine-ablation dose.Although we strongly support the goal of eliminating unnecessary radiotherapy for patients with low-risk thyroid cancer, high-quality study planning and monitoring and appropriate follow-up will be vital in the determination of how best to achieve this goal.
Expansion of the indications for endoscopic mucosal resection in patients with superficial esophageal carcinoma
Authors: K. Higuchi, S. Tanabe, W. Koizumi, T. Sasaki, K. Nakatani, K. Saigenji, N. Kobayashi, H. Mitomi
Journal: Endoscopy (2007)

Endoscopic mucosal resection (EMR) is a minimally invasive local treatment for superficial esophageal carcinoma (SEC). The use of EMR in patients with m3 or sm1 SEC remains controversial, however. The aim of this retrospective study was to evaluate the histopathological risk factors for lymph-node metastasis and recurrence in patients with m3 or sm1 SEC.The study subjects were 43 patients with m3 or sm1 esophageal squamous-cell carcinomas: 23 patients were treated surgically (the surgery group), and 20 were treated by EMR (the EMR group). We assessed the following variables of the specimens resected by surgery or EMR: tumor depth, maximal surface diameter of the tumor (superficial size), maximum diameter of tumor invasion at the lamina muscularis mucosae (LMM invasion width), and lymphatic invasion. The relationships of these variables to lymph-node metastasis and recurrence were examined.In the surgery group, lymph-node metastasis was found in four patients, all of whom had tumors with lymphatic invasion, a superficial size of at least 25 mm, and an LMM invasion width of at least 2500 microm. In the EMR group, no patient met all three of these criteria, and there was no evidence of lymph-node metastasis or distant metastasis on follow-up after EMR (median follow-up 39 months).In patients with m3 or sm1 SEC, tumors that have lymphatic invasion, larger superficial size, and wider LMM invasion are associated with a high risk for lymph-node metastasis. EMR might be indicated for the treatment of patients with m3 or sm1 SECs without these characteristics.
Congenital Absence of the Vagina
Authors: James E. Griffin, Creighton Edwards, James D. Madden, Mary Jo Harrod, Jean D. Wilson
Journal: Annals of Internal Medicine (1976)

We describe 14 patients with congenital absence of the vagina associated with a variable abnormality of the uterus and review the literature. Associated developmental anomalies of the urinary tract and skeleton are common. As a result of the analysis of two affected families, we believe that the disorder may represent the variable manifestation of a single underlying genetic defect that can be expressed alone or in any combination of vertebral, renal, and genital abnormalities. Some affected persons may have lethal manifestations such as absence of both kidneys, and some cases may result from multifactoral causes rather than a single gene defect. Whatever the cause, the defect involves mesodermal development and the mesonephric kidney, the latter resulting in abnormalities in the paramesonephros (uterus and vagina) and in the metanephric kidney. Both nonoperative and surgical treatments are generally successful in repairing the vaginal abnormality.
Israel attacks Red Cross ambulances
Authors: Owen Dyer
Journal: BMJ (2006)

The first reports of attacks on Lebanese medical staff emerged last weekend, as Israeli aircraft destroyed two Lebanese Red Cross ambulances that were bringing wounded civilians to the Najm Hospital in Tyre.

   ![][1] 

Ahmad Ali, whose legs were amputated at a Beirut hospital after Israeli planes hit Blida, in southern Lebanon (left), and a man in Sieff Hospital in Israel being treated for shock after rocket attacks in Safed 

Credit: AHIKAM SERI/PANOS AND AP

Six …

 [1]: /embed/graphic-1.gif
Avidin Targeting of Intraperitoneal Tumor Xenografts
Authors: Zhengsheng Yao, Meili Zhang, Harumi Sakahara, Tsuneo Saga, Yasushi Arano, Junji Konishi
Journal: JNCI Journal of the National Cancer Institute (1998)

Lectins (proteins that bind specific sugar molecules on glycoproteins and glycolipids) are expressed at various levels on the surface of tumor cells. Conjugation of cytotoxic agents to glycoproteins recognized by lectins could be useful in the treatment of tumors. Avidin (a highly glycosylated, positively charged protein found in egg white) contains terminal N-acetylglucosamine and mannose residues that bind to some lectins. In this study, we tested the ability of avidin, labeled through conjugation to radioactive biotin (a B vitamin), to target intraperitoneal tumors.Biotin was radioactively labeled with 111In. Four tumor models (one ovarian, one lung, and two colon) were established in nude mice by intraperitoneal injection of cultured cancer cells. The following two approaches were used in the intraperitoneal administration of avidin: 1) radioactive biotin-avidin conjugates were injected and 2) avidin was injected 1-24 hours before the injection of radioactive biotin (avidin pretargeting; avidin-biotin conjugates formed in vivo). The distribution of injected radioactivity in the tissues of treated animals was assessed.Radiolabeled avidin localized highly and rapidly in the tumors. More than 50% of the administered dose of avidin-biotin conjugate accumulated per gram of tumor tissue 2 hours after injection; high tumor uptake of radioactivity was observed up to 24 hours after conjugate injection. In contrast, accumulation of radioactivity in normal tissues was low, yielding high tumor to nontumor ratios. With avidin pretargeting, accumulation of radioactivity in the liver, kidney, and spleen was reduced to a greater extent than that in the tumor, and tumor to nontumor ratios were increased.Avidin may be a promising vehicle for the delivery of radioisotopes, drugs, toxins, or therapeutic genes to intraperitoneal tumors.
A piece of my mind. Light in the afternoon
Authors: J. D. Mull
Journal: JAMA (1988)

There was a remarkable stillness in the mosque. It did not seem possible that more than 200 people were there, seated on the floor in orderly rows, each waiting patiently for his or her special moment with the healer. A woman who looked as if she had been crying shuffled slowly forward. As she confided her story, the white-robed man with the piercing gaze leaned toward her, listening intently, and then touched her head, actually grasping it with one hand while he gently brushed her face with a peacock feather. He addressed a few words to her—words that I could not hear; he blew toward her three times; he handed her some herbs folded in a square of paper. Apparently this marked the end of the encounter, for she stood up, whispering her thanks, and another woman took her place. Again the healer leaned forward and focused intently on his
Occult Foreign Bodies in the Spinal Canal
Authors: George Ehni
Journal: New England Journal of Medicine (1983)

THE discovery of foreign bodies in the spinal canal, coupled with an inability to learn the circumstances of their introduction, is rare, judging by the small number of published accounts.1 2 3 This report describes two patients — one with scissors' tips found years after an event denied by the victim, and the other, an infant, with a broom straw in the subarachnoid space. The iron scissors' tips caused progressive myelopathy with a syrinx. The case of the infant shows how medical diagnosis and criminal investigation may fail when bizarre child abuse is found in a populous and medically acclaimed community and . . .
Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles
Authors: Shaobo Ruan, Mingqing Yuan, Li Zhang, Guanlian Hu, Jiantao Chen, Xingli Cun, Qianyu Zhang, Yuting Yang, Qin He, Huile Gao
Journal: Biomaterials (2014)
Activation of potassium channels contributes to hypoxic injury in proximal tubules.
Authors: W B Reeves, S V Shah
Journal: Journal of Clinical Investigation (1994)

The mechanisms responsible for the loss of cell potassium during renal ischemia are poorly understood. The present studies examined the hypothesis that potassium channels are activated as an early response to hypoxia and contribute to potassium loss independent from an inhibition of active K+ uptake. Potassium flux in suspensions of freshly isolated rat proximal tubules was measured using an ion-selective electrode. Exposure of the tubules to hypoxia for only 2.5 min resulted in a rise in the passive leak rate of K+ but no decrease in active K+ uptake. The passive leak of K+ was associated with a 40% decrease in cell ATP content. The passive K+ efflux was inhibited by 5 mM Ba2+ (95%) and by 15 mM tetraethylammonium (85%) suggesting that K+ channels were the primary route of K+ movement. The effects of K+ channel blockade on the development of hypoxic injury were also examined. Tetraethylammonium and glibenclamide, an inhibitor of ATP-sensitive K+ channels, reduced hypoxic injury as assessed by the release of lactate dehydrogenase or measurement of DNA damage. These results suggest that activation of K+ channels is an early response to hypoxia and contributes to hypoxic renal injury.
Restless Legs Syndrome and Spinal Anesthesia
Authors: Thomas A. Crozier, Desiree Karimdadian, Svenja Happe
Journal: New England Journal of Medicine (2008)

To the Editor: The restless legs syndrome (RLS) is a common sensorimotor disorder of unknown cause affecting approximately 10% of the population.1 One uncontrolled study showed that spinal anesthesia caused postoperative RLS.2 We conducted a prospective study to determine whether the occurrence of postoperative RLS was associated with the type of anesthesia. Patients scheduled for surgery and general or spinal anesthesia were recruited from our hospital's lists of patients undergoing elective surgery (Table 1). Using a standardized questionnaire (see the Supplementary Appendix, available with the full text of this letter at www.nejm.org), one of us interviewed patients — on admission and . . .
Abstract 1828: Omega-3 fatty acids delay the growth of mammary tumors in MMTV-Erbb2 mice
Authors: Jing Wang, Chunlan Zhang, Guorui Deng, Yong Chen, Isabelle Berquin
Journal: Cancer Research (2011)

Abstract Purpose: Dietary fats have long been suspected of contributing to breast cancer risk, but the effects of various fatty acids are still not clear. We used MMTV-Erbb2 transgenic mice to determine how different fatty acids influence mammary tumor development and what the possible mechanisms are. Methods and Results: Female MMTV-Erbb2 transgenic mice (FVB-Tg(MMTV-Erbb2)NK1Mul/J, n=13-14 per group) were placed on defined diets with 30% calories from fat, enriched in different types of fatty acids: saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), omega-3 polyunsaturated fatty acids (n-3 PUFA), omega-6 polyunsaturated fatty acids (n-6 PUFA) and control diet with a nutritionally balanced mixture of the above fatty acids. The results showed that the incidence of palpable mammary tumors, their multiplicity and average tumor weight were significantly lower in the n-3 PUFA enriched diet group than in other diet groups (p&amp;lt;0.05, ANOVA). Moreover, the tumors from the n-3 PUFA diet group showed decreased cell proliferation and increased apoptosis (as determined by immunohistochemical staining for Ki67 and cleaved caspase3, respectively) compared to other groups. However, there were no significant differences in the number of hyperplasic nodules detected in mammary glands by carmine alum whole mount staining. SFA, MUFA and n-6 PUFA were not statistically different from control. Conclusions: Our results suggest that n-3 PUFA can inhibit HER-2/neu-induced mammary tumor growth in this mouse model, but that n-3 PUFA has no effect on the very early stage of tumorigenesis. The mechanism of the antitumor effects of n-3 PUFA may be related to inhibition of cell proliferation and promotion of apoptosis. This project was supported by an Intramural Research Support Grant (Kulynych Fund) entitled: “Pilot study on the effects of different dietary fatty acids on mammary cancer risk”. 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 1828. doi:10.1158/1538-7445.AM2011-1828
Spontaneous bacterial empyema in cirrhotic patients: A prospective study
Authors: X Xiol, J M Castellví, J Guardiola, E Sesé, J Castellote, A Perelló, X Cervantes, M J Iborra
Journal: Hepatology (1996)

Spontaneous bacterial empyema (SBEM) is an infection of a preexisting hydrothorax in cirrhotic patients and has seldom been reported. To determine its incidence and primary characteristics, all cirrhotic patients with pleural effusion underwent thoracentesis at our hospital either on admission or when an infection was suspected. Pleural fluid (PF) study included biochemical analysis, polymorphonuclear (PMN) leukocyte count, and culture by two methods: conventional and modified (inoculation of 10 mL of PF into a blood culture bottle at the bedside). SBEM was defined according to previously reported criteria: PF culture positive or PMN count greater than 500 cells/micro L, and exclusion of parapneumonic effusions. Sixteen of the 120 (13 percent) cirrhotic patients admitted with hydrothorax had 24 episodes of SBEM. In 10 of the 24 episodes (43 percent), SBEM was not associated with spontaneous bacterial peritonitis (SBP). PF culture was positive by the conventional method in 8 episodes (33 percent) and by the modified method (blood culture inoculation) in 18 (75 percent) (P = .004, McNemar). The microorganisms identified in PF were Escherichia coli in 8 episodes, Streptococcus species in 4, Enterococcus species in 3, Klebsiella pneumoniae in 2, and Pseudomonas stutzeri in 1. All episodes were treated with antibiotics without inserting a chest tube in any case. Mortality during treatment was 20 percent. We conclude that SBEM is a common complication of cirrhotic patients with hydrothorax. Almost half of the episodes were not associated with SBP; thus, thoracentesis should be performed in patients with cirrhosis, pleural effusion, and suspected infection. Culture of PF should be performed by inoculating 10 mL into a blood culture bottle at the bedside.