tbuckley/cabot-search huggingface dataset:
RASSF4/AD037 Is a Potential Ras Effector/Tumor Suppressor of the RASSF Family
Authors: Kristin Eckfeld, Luke Hesson, Michele D. Vos, Ivan Bieche, Farida Latif, Geoffrey J. Clark
Journal: Cancer Research (2004)

Abstract Activated Ras proteins interact with a broad range of effector proteins to induce a diverse series of biological consequences. Although typically associated with enhanced growth and transformation, activated Ras may also induce growth antagonistic effects such as senescence or apoptosis. It is now apparent that some of the growth-inhibitory properties of Ras are mediated via the RASSF family of Ras effector/tumor suppressors. To date, four members of this family have been identified (Nore1, RASSF1, RASSF2, and RASSF3). We now identify a fifth member of this group, RASSF4 (AD037). RASSF4 shows approximately 25% identity with RASSF1A and 60% identity with RASSF2. RASSF4 binds directly to activated K-Ras in a GTP-dependent manner via the effector domain, thus exhibiting the basic properties of a Ras effector. Overexpression of RASSF4 induces Ras-dependent apoptosis in 293-T cells and inhibits the growth of human tumor cell lines. Although broadly expressed in normal tissue, RASSF4 is frequently down-regulated by promoter methylation in human tumor cells. Thus, RASSF4 appears to be a new member of the RASSF family of potential Ras effector/tumor suppressors.
Ian Campbell Coombs
Authors: John Young, Paul Davis, A T B Moir
Journal: BMJ (2005)

​FormerFormer general practitioner Warrington, Cheshire (b Warrington 1938; q Edinburgh 1963), d 26 January 2005.




Figure 1




Ian held house posts at the Eastern General Hospital, Edinburgh, and then as a school medical officer. In 1965 he became a principal in general practice in Warrington. Disability from continuing ill health forced him to retire in 1984. He was initially a keen sportsman and later a keen bridge player. After retirement he continued social bridge and chess, and maintained his lifelong love of music and stamp collecting. He leaves a wife, Una; three children; and four grandchildren.
Intrahepatic delivery of α-galactosylceramide-pulsed dendritic cells suppresses liver tumor
Authors: Tomohide Tatsumi, Tetsuo Takehara, Shinjiro Yamaguchi, Akira Sasakawa, Ryotaro Sakamori, Kazuyoshi Ohkawa, Keisuke Kohga, Akio Uemura, Norio Hayashi
Journal: Hepatology (2006)

Alpha-galactosylceramide, a glycosphingolipid, mediates interaction of dendritic cells (DCs) and NKT cells, leading to activation of both innate and acquired immunity. For cancer treatment, conventional DC-based vaccine has been tried, but its clinical efficacy is limited against liver cancer. Intrahepatic injection of alpha-Galactosylceramide-pulsed DCs (alphaGCDC) has not yet been tested in the liver that contains abundant immune cells such as NK, NKT, and T cells. In the present study, we examined the efficacy of alphaGCDC administration in comparison with p53 peptide-pulsed DCs using a well-established murine CMS4 tumor model. Injection of alphaGCDC into CMS4 liver tumors resulted in complete tumor rejection and established long-term survival of the animals, while injection of p53(232-240) peptide-pulsed DCs (pepDC) only partially suppressed tumor growth in the liver. The levels of IFN-gamma in sera of alphaGCDC-treated mice were significantly higher than those of pepDC-treated mice. Hepatic NK cells were efficiently activated by alphaGCDC injection and played a critical role in liver tumor rejection as evidenced by an in vivo antibody-mediated NK cell depletion study. Injection of alphaGCDC into liver tumor led to higher p53(232-240) peptide-specific CD8+ T cell response than that of pepDC. The mice that had been protected from CMS4 liver tumor by alphaGCDC injection became resistant to subcutaneous CMS4 rechallenge, but not to Colon26 rechallenge.These results demonstrate that alphaGCDC injection into the liver can efficiently activate NK cells that in turn reject liver tumors to establish potent acquired immunity against the original tumor.
The long and winding road for the Fukushima nuclear workers
Authors: Tetsuya Tanimoto, Koichiro Yuji, Yuko Kodama, Tomoko Matsumura, Hisashi Yamamoto, Jinichi Mori, Miwako Hosoda, Naoyuki Uchida, Masahiro Kami, Shuichi Taniguchi
Journal: The Lancet (2012)
Differential activation of matrix metalloproteinases in heart failure with and without ventricular dilatation
Authors: N Nishikawa
Journal: Cardiovascular Research (2003)

Objective: Remodeling of extracellular matrix (ECM) is considered to contribute to progression of left ventricular (LV) remodeling and matrix metalloproteinases (MMPs) play crucial roles in regulation of ECM. Activation of MMPs is observed in systolic heart failure (SHF) and is suggested to be responsible for LV dilatation in SHF. Diastolic heart failure (DHF) that is not associated with LV dilatation is also accompanied with collagen accumulation; however, differences in ECM regulatory system, especially activation of MMPs, between SHF and DHF remain to be clarified. This study was conducted to clarify whether MMPs are activated even in DHF, and if so, to characterize the difference in activation of MMPs between SHF and DHF for identification of a target for the prevention of LV remodeling in SHF. Methods: To exclude effects of differences in underling cardiovascular diseases and genetic background on the comparison between DHF and SHF, we used Dahl salt-sensitive rats fed on high salt diet starting at 7 weeks of age as DHF model and at 8 weeks as SHF model, both of which our laboratory recently developed. Results: LV fibrosis progressed in the DHF and SHF model rats. MMP-2 was activated to the same degree in both rats. Activation of MMP-9 was enhanced in the DHF model rats, but the activity was more enhanced in the SHF rats. Film in situ zymography showed that enhanced gelatinolytic activity appeared only in the mid layer of the LV wall in the DHF rats and throughout the wall in the SHF rats. The distribution of gelatinolytic activity was consistent with that of expression of MMP-9 as assessed in immunohistochemical study. Conclusions: MMP-9 rather than MMP-2 may be involved in LV dilatation in SHF and be a specific target for the prevention of LV remodeling.
Persistent antigen at vaccination sites induces tumor-specific CD8+ T cell sequestration, dysfunction and deletion
Authors: Yared Hailemichael, Zhimin Dai, Nina Jaffarzad, Yang Ye, Miguel A Medina, Xue-Fei Huang, Stephanie M Dorta-Estremera, Nathaniel R Greeley, Giovanni Nitti, Weiyi Peng, Chengwen Liu, Yanyan Lou, Zhiqiang Wang, Wencai Ma, Brian Rabinovich, Ryan T Sowell, Kimberly S Schluns, Richard E Davis, Patrick Hwu, Willem W Overwijk
Journal: Nature Medicine (2013)
Art: Everything I Could Buy on eBayTM about Malaria
Authors: C. McKenna
Journal: BMJ (2002)

Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Short of cash? Then why not sell your soul? The going rate for souls, almost new, in good condition, is £11.61 on eBay, the world's largest online auction house. So diverse are the items on sale that NASA has recently admitted to searching eBay for replacement computer parts for the space shuttle programme. Now Canadian artist Bill Burns has joined the devotees of the auction house and has amassed an eclectic and eccentric cornucopia of items relating to malaria for this Wellcome Trust exhibition. The items on display amount to a veritable pocket history of malaria and malaria prevention and treatment programmes in the 20th century. One can see model crop dusters designed to spray DDT (dichlorodiphenyltrichloromethane), stamps from around the world featuring malaria themes, maps circa 1960 of … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
A CASE OF MYXEDEMA WITH PROMINENT NASAL SYMPTOMS.
Authors: A. H. CLEVELAND
Journal: JAMA (1898)

The fact that the nasal condition was the only reason why this patient sought relief and that this seems to be so entirely dependent upon the general disorder leads me to report the history, which is as follows: Mrs. I., age 38, was first seen Sept. 9, 1896. She complained of nasal stoppage with attacks of sneezing and watery discharge following an attack of grippe in May and persisting since then. For the past three weeks it had been worse. Examination of the nostrils at this time showed large boggy turbinates on both sides, rather worse on right, with a waxy paleness of the entire mucous membrane of the nostrils. Several constitutional remedies, as well as local applications, were tried in succession without the slightest effect on the condition. Oct. 26, 1896, frost having eliminated a possible hay fever and the hoped-for improvement not having occurred, I examined the nostrils
TREATMENT OF MYASTHENIA GRAVIS
Authors: CHARLES T. STONE
Journal: JAMA (1949)

Myasthenia gravis is a rare disease. Viets1has estimated that the total number of cases in the United States is about 1,500. In spite of this, there is widespread interest in the disease because of the challenge presented with regard to its cause and treatment, because of the complex nature of the pathologic physiology involved and because modern advances in biologic chemistry have afforded a new array of technics for its study. Consequently, there is considerable literature dealing with the condition from groups of investigators with widely differing interests and approaches.  CLINICAL FEATURES  The classic clinical picture of myasthenia gravis permits its easy recognition. The undue fatigue of voluntary muscles after exercise, their return to normal or near normal after rest, the absence of muscular atrophy, the mildness of symptoms in the forenoon as compared with the afternoon and evening, the variable clinical course which may be interspersed with
Envisioning Sophisticated Electronic Health Records through the Lens of Health Care Reform
Authors: Curtis H. Weiss, Luís A. Nunes Amaral
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (K23HL118139) and the Parker B. Francis Fellowship Program (C.H.W.).



Author disclosures are available with the text of this article at www.atsjournals.org.
Akathisia From Prochlorperazine
Authors: Peter Weiden
Journal: JAMA (1985)

<h3>To the Editor.—Report of a Case.—</h3> A 26-year-old man with multiple hospitalizations for chemotherapy of stage IV lymphoma experienced a severe subjective sense of restlessness and anxiety. "I feel like jumping out of my skin.... I can't stand this hospital anymore." These complaints were considered to be secondary to his anxiety about his illness and prognosis. However, the restlessness was a distinct change from his behavior during previous hospitalizations and coincided with administration of prochlorperazine (Compazine), 10 mg intravenously every six hours, for nausea. A tentative diagnosis of drug-induced akathisia was made, prochlorperazine treatment was discontinued, and the restlessness completely abated within three days. <h3>Comment.—</h3> Extrapyramidal reactions can occur from dopamine blocking agents such as prochlorperazine or metoclopramide, which are commonly used as antiemetics.<sup>1</sup>However, it has been my experience as well as others'<sup>2</sup>that akathisia, an intense and highly distressing subjective sense of restlessness, is the side
Reliability of absent platelet dense bodies as a diagnostic criterion for Hermansky‐Pudlak syndrome
Authors: Carl J. Witkop, Marcy Krumwiede, Heddie Sedano, James G. White
Journal: American Journal of Hematology (1987)

Abstract The clinical, pigmentary, and ceroid storage manifestations of the Hermansky‐Pudlak syndrome (HPS) triad of albinism, hemorrhagic diathesis, and ceroid storage disease are variable. Therefore, a rapid and accurate method of diagnosing HPS is needed. Platelets of 66 albinos were examined by electron microscopy for the presence or absence of dense bodies. Results show that patients reexamined over a period of 1 year had consistent findings. Those lacking dense bodies (15) when first examined also lacked dense bodies when reexamined a year later, and they had evidence of ceroid storage. Those with dense bodies when first examined (8) also had dense bodies when reexamined, did not have evidence of storage disease, and had types of albinism other than HPS. Of 20 propositi lacking dense bodies, all 32 albino relatives also lacked dense bodies, while 6 albino relatives of 6 propositi with dense bodies also had dense bodies in their platelets. The evidence supports the concept that HPS is a distinct genetic and biochemical disease in which the components of the triad are the result of a single genetic defect, either a point mutation or a small deletion. Comparison of whole mount preparations with thin section preparations of 13 albinos shows that whole mount preparations are an accurate and rapid method for diagnosing HPS. The most consistent diagnostic feature of HPS is lack of platelet dense bodies.
Virus-induced alterations in cyclic adenosine monophosphate generation in hamster islets of Langerhans.
Authors: E J Rayfield, K J Kelly
Journal: Journal of Clinical Investigation (1986)

Inoculation of golden Syrian hamsters with Venezuelan encephalitis (VE) virus results in a sustained diminution in glucose-stimulated insulin release that is correctable by cyclic (c) AMP analogs and phosphodiesterase inhibitors. This suggested the importance of directly measuring cAMP content in VE-infected and control islets in response to insulin secretagogues. The basal cAMP content of VE-infected islets (0.14 +/- 0.02 pmol/micrograms islet DNA) was approximately half that of control islets (0.27 +/- 0.02 pmol/micrograms islet DNA) (P less than 0.05). In the presence of 10 microM glucagon (and 3 mM glucose), the rate of cAMP generation in VE-infected islets was only half that of control islets. With 10 mM alpha-ketoisocaproic acid, the rates of cAMP generation were indistinguishable between control and experimental groups. In response to 20 mM glucose and 3-isobutyl-1-methylxanthine (IBMX) (a phosphodiesterase inhibitor), cAMP generation in VE-infected islets was 81% (NS) of the control rate. When a more specific phosphodiesterase inhibitor, RO 20-1724, was used with 20 mM glucose, cAMP generation in the infected islets was only 44% (P less than 0.001) of the control value. Insulin secretion over the perifusion period paralleled the cAMP levels. In the presence of 10 mM alpha-ketoisocaproic acid, there was no difference in insulin secretion between VE-infected and control islets, while there was a statistically significant (P less than 0.05) difference with 10 microM glucagon or 20 mM glucose (in 1 mM RO 20-1724). These data point to a defect in the cAMP generation system of VE-infected islets, although additional factors involved in insulin secretion may also be impaired by the virus.
Tobacco, Public Health, and the FDA
Authors: Gregory D. Curfman, Stephen Morrissey, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2009)

More than a decade ago, David Kessler, then Commissioner of the Food and Drug Administration (FDA), launched a bold initiative to regulate tobacco. He believed that since nicotine is an addictive substance, it fell under the statutory authority of the FDA to regulate it as a drug and cigarettes as the delivery vehicle. His effort failed, however, when the U.S. Supreme Court decided in a 5-to-4 ruling (FDA v. Brown & Williamson Tobacco Corp.) that the Food, Drug, and Cosmetic Act of 1938, which defined the FDA's authority, did not grant the agency jurisdiction to regulate tobacco. Writing . . .
Resuscitation needed for the curriculum?
Authors: P J Baskett
Journal: BMJ (1985)

Resuscitation needed for the curriculum?The paper by Skinner, Camm, and Miles in this issue on the calibre of resuscitation skills found among preregistration house officers at one ofour premier teaching hospitals should provide some thought and some activity from the designers of the medical schools' curriculum (p 1549).The investigators found that a mere 55% of their preregistration house officers could perform the techniques of basic life support: clearance and maintenance of the airway, artificial ventilation by the mouth to mouth method, and external compression of the chest.Theirs is not an isolated finding.Casey found even poorer standards in a comparable group of doctors at Cambridge,' and in 1981 Lowenstein and his colleagues reported that junior residents in a big centre in the United States had similarly ineffective capabilities.2Nor are our young doctors proficient at advanced life support skills, where one might suppose they would come into their own.Skinner et al show that only one in three could pass an endotracheal tube-and that they took an inordinately long time about it.None would have passed the American Heart Association's advanced cardiac life support examination.Clearly, then, the standards of resuscitation performance among the junior medical staff in Britain leave a lot of room for improvement.Since the general educational standard of our graduates is extremely high in other respects, the fault must surely lie in medical schools not placing sufficient emphasis on this subject.A survey by questionnaire sent to 30 medical schools in Britain by Smith and Hill from the Southampton Anaesthetic Department produced 18 replies (personal communication).Of these, two thirds offered some training in first aid, but the course was compulsory in only two.All schools claimed to offer training in resuscitation, but the course was compulsory in only eight, and the students' knowledge and ability were assessed in only four centres.Most schools did not offer any training at all until the student was well into the clinical years.
The Blood Bank and Homologous Serum Jaundice
Authors: John B. Alsever
Journal: New England Journal of Medicine (1959)

UNDOUBTEDLY the most unsatisfactory situation in blood banking today is the inability to exercise any real control over the hazard of transmitting homologous serum jaundice by whole-blood transfusions. The risk is inherent in every bottle of blood issued. The problems of control are multiple: no donor's history is really reliable; any donor may be an innocent carrier; no laboratory test, or group of tests, is specific for the virus of hepatitis; there is no way of treating the blood to kill the virus without violating essential storage or safety requirements for whole blood; there is no susceptible laboratory test animal . . .
Dutch health insurer ranks hospitals on breast cancer surgery
Authors: T. Sheldon
Journal: BMJ (2010)

Courts in the Netherlands have ruled that one of the country’s largest health insurers can publish on its website its ranking of hospitals for breast cancer surgery.

Centraal Zorgverzekeraar (Central Health Insurer) (CZ) ranks 93 hospitals in four categories: “best,” “good,” “can do better,” and those with which it will “no longer contract.” The rankings are based principally on the volume of operations performed each year (www.cz.nl/overzicht-beste-borstkankerzorg).

The insurer sparked a public debate after it announced that from 2011 it would not sign contracts for breast cancer treatment with six hospitals (later reduced to four) because it judged that at least 70 operations a …
Extensive polymorphisms observed in HIV–1 clade B protease gene using high–density oligonucleotide arrays
Authors: Michael J. Kozal, Nila Shah, Naiping Shen, Robert Yang, Raymond Fucini, Thomas C. Merigan, Douglas D. Richman, Don Morris, Earl Hubbell, Mark Chee, Thomas R. Gingeras
Journal: Nature Medicine (1996)
A CASE OF DUODENAL DIVERTICULUM
Authors: DUNLAP P. PENHALLOW
Journal: JAMA (1923)

The subject of duodenal diverticula is one which is of great interest not only to the gastro-enterologist but to the surgeon as well. This condition, while rare, has been recognized for many years, and more especially since the advent of the roentgen ray in the diagnosis of pathologic gastro-intestinal conditions.  No attempt is made, in reporting this case, to theorize on the causative factors of this condition or completely to review the literature on the subject, as this has been rather recently done by Andrews, 1 from an historical standpoint and also from more recent statistics. In his review, he says:  Luismayer had 1,367 necropsies which yielded forty-five cases of diverticula, or 3 per cent. Buschi found 2 per cent. in all his researches, or a total of seventy-three cases, only fifty-four of which had clinical symptoms. Up to the time of this report (1911), no one author had had
Cyclooxygenase-1 Deficiency in Bone Marrow Cells Increases Early Atherosclerosis in Apolipoprotein E– and Low-Density Lipoprotein Receptor–Null Mice
Authors: Vladimir R. Babaev, Lei Ding, Jeff Reese, Jason D. Morrow, Matthew D. Breyer, Sudhansu K. Dey, Sergio Fazio, MacRae F. Linton
Journal: Circulation (2005)

Cyclooxygenase-1 (COX-1) has been implicated in the pathogenesis of atherothrombosis and is expressed by the major cell types of atherosclerotic lesions. COX-1-mediated platelet thromboxane (TX) production has been proposed to promote both early atherosclerosis and thrombosis. Here, we examined the impact of COX-1 deficiency in bone marrow-derived cells on early atherogenesis in the mouse.LDL receptor (LDLR)(-/-) and apolipoprotein E (apoE)(-/-) recipient mice were lethally irradiated and transplanted with COX-1(-/-) bone marrow. Mice reconstituted with COX-1(-/-) marrow had nearly complete (99.7%) loss of platelet TXA2 and significantly suppressed levels of macrophage and urinary TXA2 metabolites. Serum lipid levels and lipoprotein distributions did not differ between recipients reconstituted with COX-1(+/+) and COX-1(-/-) marrow. Surprisingly, the extent of atherosclerotic lesions in both LDLR(-/-) and apoE(-/-) mice reconstituted with COX-1(-/-) marrow was increased significantly compared with control mice transplanted with COX-1(+/+) marrow. Peritoneal macrophages isolated from LDLR(-/-) mice reconstituted with COX-1(-/-) marrow had increased lipopolysaccharide-induced levels of COX-2 mRNA and protein expression. Fetal liver cell transplantation studies revealed a 30% increase in atherosclerosis in COX-1(-/-)-->LDLR(-/-)mice compared with COX-1(+/+)-->LDLR(-/-)mice, whereas the extent of atherosclerosis was unchanged in COX-1(-/-)/COX-2(-/-)-->LDLR(-/-)mice.COX-1 deficiency in bone marrow-derived cells worsens early atherosclerosis in apoE(-/-) and LDLR(-/-) mice despite virtual elimination of platelet TX production. These data demonstrate that platelet TX production does not aggravate early atherosclerotic lesion formation and that upregulation of COX-2 expression in COX-1(-/-) macrophages is proatherogenic.
Phenolsulfonphthalein Excretion Tests
Authors: D. Robert Axelrod
Journal: JAMA (1966)

To the Editor:—  Phenolsulfonphthalein (PSP) excretion tests were discussed inThe Journal( 195 : 1078, 1966). I recently reevaluated this subject ( Arch Int Med  117 :74, 1966).  The amount of dye excreted by the kidney in the first 15 minutes after its intravenous administration is a good index of renal tubular function. However, the voided specimen at 15 minutes may not reflect the renal function. Decreased dye in that specimen can be due to incomplete bladder emptying or a slow rate of urine formation. Incomplete bladder emptying can be detected by finding decreased dye excretion in the first 15-minute specimen and normal excretion in one or two hours. (PSP, not promptly excreted by the kidneys, [1] is excreted by the liver and [2] diffuses out of the plasma. With the falling plasma level, progressively less dye is available for renal excretion.) The reason for having the patient empty his bladder before