tbuckley/cabot-search huggingface dataset:
Mice Lacking the MHC Class II Transactivator (CIITA) Show Tissue-Specific Impairment of MHC Class II Expression
Authors: Cheong-Hee Chang, Sylvie Guerder, Soon-Cheol Hong, Willem van Ewijk, Richard A Flavell
Journal: Immunity (1996)

CIITA activates the expression of multiple genes involved in antigen presentation and it is believed to be required for both constitutive and IFNγ-inducible expression of these genes. To understand the role of CIITA in vivo, we have used gene targeting to generate mice that lack CIITA. CIITA-deficient (−/−) mice do not express conventional MHC class II molecules on the surface of splenic B cells and dendritic cells. In addition, macrophages resident in the peritoneal cavity do not express MHC class II molecules upon IFNγ stimulation nor do somatic tissues of mice injected with IFNγ, in contrast with wild-type mice. The levels of Ii and H-2M gene transcripts are substantially decreased but not absent in CIITA (−/−) mice. The transcription of nonconventional MHC class II genes is, however, not affected by CIITA deficiency. A subset of thymic epithelial cells express MHC class II molecules. Nonetheless, very few mature CD4 T cells are present in the periphery of CIITA (−/−) mice despite MHC class II expression in the thymus. Consequently, CIITA (−/−) mice are impaired in T-dependent antigen responses and MHC class II–mediated allogeneic reponses.
HSP90 Supports Tumor Growth and Angiogenesis through PRKD2 Protein Stabilization
Authors: Ninel Azoitei, Kristina Diepold, Cornelia Brunner, Arefeh Rouhi, Felicitas Genze, Alexander Becher, Hans Kestler, Johan van Lint, Gabriela Chiosis, John Koren, Stefan Fröhling, Claudia Scholl, Thomas Seufferlein
Journal: Cancer Research (2014)

Abstract The kinase PRKD2 (protein kinase D) is a crucial regulator of tumor cell-endothelial cell communication in gastrointestinal tumors and glioblastomas, but its mechanistic contributions to malignant development are not understood. Here, we report that the oncogenic chaperone HSP90 binds to and stabilizes PRKD2 in human cancer cells. Pharmacologic inhibition of HSP90 with structurally divergent small molecules currently in clinical development triggered proteasome-dependent degradation of PRKD2, augmenting apoptosis in human cancer cells of various tissue origins. Conversely, ectopic expression of PRKD2 protected cancer cells from the apoptotic effects of HSP90 abrogation, restoring blood vessel formation in two preclinical models of solid tumors. Mechanistic studies revealed that PRKD2 is essential for hypoxia-induced accumulation of hypoxia-inducible factor-1α (HIF1α) and activation of NF-κB in tumor cells. Notably, ectopic expression of PRKD2 was able to partially restore HIF1α and secreted VEGF-A levels in hypoxic cancer cells treated with HSP90 inhibitors. Taken together, our findings indicate that signals from hypoxia and HSP90 pathways are interconnected and funneled by PRKD2 into the NF-κB/VEGF-A signaling axis to promote tumor angiogenesis and tumor growth. Cancer Res; 74(23); 7125–36. ©2014 AACR.
Abstract 5020: Potential lifestyle intervention in inner city women with endometrial cancer: A pilot study
Authors: Nicole S. Nevadunsky, Gloria Huang, Yvy Rivera, Alyson Moadel, Dennis Kuo, Kimala Harris, Gary Goldberg
Journal: Cancer Research (2011)

Abstract Hypothesis: Evidence suggests that modification of diet and exercise practices may prevent cancer recurrence. It may also decrease the risk factors for the leading causes of death in women including heart disease and stroke. Methods: 100 patients with previously diagnosed endometrial cancer were enrolled in a pilot study to collect data regarding current lifestyle, willingness to change and preferred programs of nutrition and exercise. All enrolled subjects were verbally asked to respond to a questionnaire that included validated and novel instruments. Results: Mean age was 64 (39-86 years) and mean body mass index was 34 kg/m2 (17-55). 38% of the responders were Black/African American, 33% were Caucasian, and 21% were Hispanic. Of these, 69% were born in the United States of America. 75% described themselves as “overweight”. The most common mode of current exercise was walking (54%). 89% of the patients responded that they would be interested in participating in a diet or exercise program. The most common reason that women stated they would want to participate was to improve overall health (48%). Only 4% stated that they thought it would prevent recurrence of their cancers. Diabetes mellitus was previously diagnosed in 30% of participants. Eighty three percent of diabetic patients had body mass index over 30 kg/m2 and 30% had body mass index over 40 kg/m2. Eleven patients currently on therapy for diabetes had hemoglobin A1C values greater then 6.5 and are at risk for microvessel damage and end-organ dysfunction including kidney failure and impaired vision Discussion: These data present the opinions of a racially heterogeneous group of women at risk for cancer recurrence, as well as the morbidity and mortality related to obesity and diabetes. These data suggest that women at our center should participate in a dietary and exercise intervention program and our patients would benefit from the additional health education. 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 5020. doi:10.1158/1538-7445.AM2011-5020
Fatal encephalitis apparently due to rabies. Occurrence after treatment with human diploid cell vaccine but not rabies immune globulin
Authors: J. Devriendt
Journal: JAMA (1982)

We describe a case of fatal encephalitis apparently due to rabies despite treatment with human diploid cell vaccine from the day of exposure but without rabies immune globulin (or serum). This case reinforces the need for rabies immune globulin as part of rabies treatment. (<i>JAMA</i>1982;248:2304-2306)
Doctors must speak out over war and humanitarian crises
Authors: L. Eaton
Journal: BMJ (2001)

Doctors have a duty to speak out about their concerns over war and humanitarian crises—if they don't they are just storing up problems for future generations. And medical students should be taught more about global health issues, so they have a better understanding of international health.

Those were the messages from forensic psychiatrist Jack Piachaud, speaking at a meeting organised by the Open Section of the Royal Society of Medicine in London this week.

The seminar was examining the rights and wrongs of providing humanitarian …
c-Jun Triggers Apoptosis in Human Vascular Endothelial Cells
Authors: Nanping Wang, Lynne Verna, Stephen Hardy, Yi Zhu, Kuo-Sheng Ma, Michael J. Birrer, Michael B. Stemerman
Journal: Circulation Research (1999)

Abstract —In endothelial cells (ECs), the transcription factor c-Jun is induced by a variety of stimuli that perturb EC function. To extend our understanding of the role of c-Jun in EC physiology, we have directed overexpression of c-Jun in human umbilical vein ECs by using a tetracycline-regulated adenoviral expression system. In this study, we report a novel observation using this system. Specific expression of c-Jun is a sufficient trigger for ECs to undergo apoptosis, as demonstrated by a set of combined assays including an ELISA specific for histone-associated DNA fragmentation, DNA laddering, and TdT-mediated dUTP nick end labeling (TUNEL). Tetracycline can effectively shut off c-Jun overexpression and prevent EC apoptosis. Cleavage of poly(ADP-ribose) polymerase was also detected in ECs overexpressing c-Jun. Moreover, inhibitors of cysteine proteases blocked the apoptosis, suggesting a caspase-associated mechanism involved in proapoptotic effects of c-Jun. To gain further insight into the role of c-Jun as a pathophysiological regulator of EC death, TAM67, a dominant-negative mutant of c-Jun, was overexpressed in human umbilical vein ECs to abrogate endogenous c-Jun/activator protein-1 activation. H 2 O 2 -triggered apoptosis was largely attenuated in ECs overexpressing TAM67. Together, these results suggest that c-Jun, as a proapoptotic molecule, may play a role in mediating the cell death program in vascular endothelium.
Failure of Aureomycin in Experimental Melioidosis
Authors: J. C. Cruickshank
Journal: BMJ (1949)

POLIOMYELITIS IN NEW ZEALAND ME 8 were completely recovered, 7 still moderately paralysed, and 5 severely paralysed.Hence out of 224 patients 12 died and after 12 months 32 (14.2%) still had residual weakness.The remainder had made a complete recovery.It is a pleasure to express one's appreciation of Dr. Elizabeth Hughes, with whom I worked in this epidemic; Dr.
Learning Theories and Medical Lectures: Add Little to Little and There Will Be a Big Pile-Reply
Authors: R. I. Cook
Journal: JAMA (1989)

<h3>In Reply. —</h3> I appreciate the comments of Dr Wallach and Ms Dyer. I do not agree that present medical students are inferior to their predecessors. Those of my acquaintance are enthusiastic, bright, and dedicated to the difficult task of becoming a physician. I agree with Dr Wallach that learning by medical students is of overriding importance. Lectures are a major part of the educational curriculum and, unlike other factors, the style of lecture presentation remains completely under faculty control. The exercise of this control reflects on the medical school faculty and not on the students. Ms Dyer describes yet another style of lecture presentation, although this may be a variation on the diffusionist theme. She also has identified a major issue in curriculum planning: the cumulative effect of lecture style. Otherwise minor characteristics of lecture style can have untoward results when lecture frequency is high. This problem is acknowledged
Abstract 1342: The NF-kappaB P50 Subunit Protects Against Remodeling and Cardiac Dysfunction Following Myocardial Infarction
Authors: Leo Timmers, J Karlijn van Keulen, Imo I Hoefer, Joost P Sluijter, Marie Jose Goumans, Pieter A Doevendans, Cees J van Echteld, Jan J Piek, Gerard Pasterkamp, Dominique P de Kleijn
Journal: Circulation (2007)

Introduction Left ventricular (LV) remodeling leads to congestive heart failure and is a main determinant of morbidity and mortality following myocardial infarction (MI). To further improve the treatment of post infarct LV remodeling, a better understanding of the molecular mechanisms involved in this complicated process is required. The nuclear factor (NF)- κB family (p50, p52, p65) usually forms dimers that regulate DNA transcription in response to a variety of stimuli including pro-inflammatory cytokines, oxidative stress and also ischemia. Inhibition of NF- κB has been shown to reduce heart failure following MI in rats. The specific role of the different NF- κB subunits during LV remodeling, however, has not been clarified thus far. In this study, we elucidate the role of the NF- κB p50 subunit in post infarct LV remodeling. Methods and Results MI was induced in wild type C57Bl6 mice and NF- κB p50 KO mice. Without affecting infarct size (45.4 ± 4.3 vs. 42.5 ± 4.6%; p=0.461), the absence of NF- κB p50 increased the extent of LV remodeling (EDV: 175 ± 13 vs. 107 ± 11 μl; p=0.005) and aggravated systolic dysfunction (LVEF: 16.1 ± 1.5 % vs. 24.7 ± 3.7%; p=0.045) 28 days following MI as assessed by magnetic resonance imaging (9.4 T). In the non-infarcted myocardium, interstitial fibrosis (1.53 ± 0.28 vs. 1.05 ± 0.15 grayvalue/μm 2 ; p=0.042) and hypertrophy (426 ± 51 vs. 251 ± 12 μm 2 /cardiomyocyte; p=0.018) were increased in NF-κB p50 KO mice. In the infarct area, however, collagen density was decreased (15.11 ± 1.16 vs. 27.28 ± 4.93 grayvalue/μm 2 ; p=0.028), which was accompanied by increased TNF-alpha mRNA expression (0.086 ± 0.04 vs. 0.026 ± 0.015; p=0.046) and increased MMP9 activity (0.31 ± 0.03 vs. 0.19 ± 0.03; p=0.049) Conclusion These data provide evidence for a protective role of NF- κB p50 in post infarct maladaptive LV remodeling, most likely by reducing inflammatory cytokine production and matrix degradation.
Cancer risks from exposure to radon in homes.
Authors: O Axelson
Journal: Environmental Health Perspectives (1995)

Exposure to radon and its decay products in mines is a well recognized risk of lung cancer in miners. A large number of epidemiologic studies from various countries are quite consistent in this respect even it the magnitude of the risk differs according to exposure levels. Indoor radon became a concern in the 1970s and about a dozen studies have been conducted since 1979, mainly of the case-control design. From first being of a simple pilot character, the designs have become increasingly sophisticated, especially with regard to exposure assessment. Crude exposure estimates based on type of house, building material and geological features have been supplemented or replaced by quite extensive measurements. Still, exposure assessment remains a difficult and uncertain issue in these studies, most of which indicate a lung cancer risk from indoor radon. Also a recent large scale study has confirmed a lung cancer risk from indoor radon. More recently there are also some studies, mainly of the correlation type, suggesting other cancers also to be related to indoor radon, especially leukemia, kidney cancer, and malignant melanoma, and some other cancers as well. The data are less consistent and much more uncertain than for indoor radon and lung cancer, however; and there is no clear support from studies of miners in this respect.
Update in Gastroenterology
Authors: Norton J. Greenberger
Journal: Annals of Internal Medicine (1997)

Updates1 February 1997Update in GastroenterologyNorton J. Greenberger, MDNorton J. Greenberger, MDFrom the University of Kansas, Kansas City, Kansas.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-3-199702010-00008 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail 1996-97 Series: John Roberts, MD, EditorAmong the advances made in the field of gastroenterology in the past year, advances in the knowledge and treatment of common upper gastrointestinal symptoms have been the most prominent. The long-term use of proton-pump inhibitors was found to be effective, and various regimens against Helicobacter pylori disease were expanded. The causes of nonulcer dyspepsia were described; even after exhaustive work-ups, however, a third of patients still had “idiopathic” dyspepsia. Advances also took place in the prevention of gallstones, the treatment of ulcerative colitis, the prevention of colon cancer in women, and the use of ... Author, Article, and Disclosure InformationAffiliations: From the University of Kansas, Kansas City, Kansas.Corresponding Author: Norton J. Greenberger, MD, Department of Medicine, University of Kansas Medical Center, 39th Street and Rainbow Boulevard, Kansas City, KS 66103.Current Author Addresses: Dr. Greenberger: Department of Medicine, University of Kansas Medical Center, 39th Street and Rainbow Boulevard, Kansas City, KS 66103. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByChronic kidney disease (CKD) in the elderly – a geriatrician's perspectiveAnalgesia in patients with ESRD: a review of available evidenceThe Role of Gastroesophageal Reflux Disease in AsthmaIrritant-Associated Vocal Cord Dysfunction 1 February 1997Volume 126, Issue 3Page: 221-225KeywordsAntibioticsAspirinColorectal cancerDrugsGastroesophageal reflux diseaseLactoseMilkPancreatitisSepsisUlcerative colitis Issue Published: 1 February 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Growth factor expression in normal, benign, and malignant breast tissue
Authors: M. T Travers, P. J Barrett-Lee, U. Berger, Y. A Luqmani, J.-C. Gazet, T. J Powles, R C. Coombes
Journal: BMJ (1988)

Several oncogenes seem to encode certain growth factors that may play a part in regulating cell growth in tumours. To assess whether such factors are synthesised endogenously by tumour cells the amounts of messenger RNA for several growth factors known to be synthesised by cancer cells of the breast in vitro were examined in biopsy specimens from 52 malignant and 15 non-malignant tumours of the breast and four samples of normal breast. Transforming growth factor beta messenger RNA was significantly more abundant in breast cancers (32 of 42 (76%) having appreciable amounts) than non-malignant breast tissue (five of 13 (38%) having similar amounts). Transcripts for both transforming growth factor alpha and its receptor, epidermal growth factor receptor, were found more commonly in carcinomas that were negative for oestrogen receptor (64% and 87%, respectively) than in those that were positive (27% and 30%, respectively). Insulin-like growth factor II messenger RNA was present in all 15 samples of non-malignant tissue but was found (in considerably lower amounts) in only 11 of 21 (52%) carcinomas. Epidermal growth factor receptor was also found in all non-malignant breast tissues, compared with 19 of 45 (42%) carcinomas. Platelet derived growth factor A and B chain transcripts coexisted in all normal and benign tissue and most carcinomas. This differing pattern of expression growth factors in tissue from malignant tumours compared with benign tumours and normal breast tissue suggests that some growth factors, particularly transforming growth factors alpha and beta, may have an important role in controlling growth of human breast cancers, particularly those that are hormone independent.
Accuracy of local data on skin cancer
Authors: J. Newton, J. Redburn
Journal: BMJ (1995)

additionally breast fed by a lactating relative or the child's natural mother.In my experience in Papua New Guinea this method worked well in all cases in which the adoptive mother was motivated and received the necessary support from her family.Side effects of the drugs used were rarely complained of, and only once was it necessary to add methyldopa in the sequence as described above.Clearly, in industrialised countries, where induction of lactation is not considered to be essential for the survival of the infant, the relative importance of side effects and concerns regarding excretion of the drugs into the milk are greater.Nevertheless, at least some of the aspects of the above method could well be adopted in in- dustrialised countries.
Gastric Cancer — New Therapeutic Options
Authors: John S. Macdonald
Journal: New England Journal of Medicine (2006)

Gastric and gastroesophageal adenocarcinomas are important health problems. A 2005 analysis1 of the worldwide incidence of and mortality from cancer showed that 934,000 cases of gastric cancer occurred in 2002 and that 700,000 patients die annually of this disease. The management of gastric cancer, like the management of most gastrointestinal cancers, is based on surgical resection of the primary tumor. When the cancer is localized to the stomach and is minimally invasive,2,3 surgical cure is possible in up to 90 percent of cases. However, the detection of early gastric cancer is unusual in Western countries. More commonly, resectable gastric . . .
Infections with Campylobacter jejuni and Campylobacter-like Organisms in Homosexual Men
Authors: THOMAS C. QUINN
Journal: Annals of Internal Medicine (1984)

In studies of the cause of gastrointestinal symptoms in homosexual men, Campylobacter jejuni was recovered from 10 of 158 men with, and 2 of 75 men without, intestinal symptoms. In addition, a heterogeneous group of Campylobacter-like organisms was identified in 26 symptomatic and 6 asymptomatic homosexual men, but in none of 150 heterosexual men and women. Infections with Campylobacter-like organisms, like infections with C. jejuni, were significantly associated with the sexual practice of anilinctus and were usually associated with diarrhea, abdominal cramps, and hematochezia; proctocolitis seen at sigmoidoscopy; increased numbers of leukocytes seen on rectal smears; acute inflammatory changes seen on rectal biopsy specimens; and a serum antibody response to the infecting organism.
DIABETIC GANGRENE IN THE SOUTH
Authors: I. I. LEMANN
Journal: JAMA (1927)

It has been suggested that a possible etiologic factor in the causation of diabetic gangrene is the state of the weather. Beard<sup>1</sup>noted that 95 per cent of the diabetic gangrene cases appearing at the University Hospital in Minneapolis entered during the winter months. Blotner and Fitz,<sup>2</sup>in reporting sixty-nine cases of diabetic gangrene at the Peter Bent Brigham Hospital in Boston, observed that their cases also showed a greater frequency in the colder months of the year than during the warmer months, though their experience was by no means as striking as that of Beard. As corroborative evidence on the importance of cold in producing diabetic gangrene, they quote McLester of Birmingham as stating that it is an extremely rare complication in his experience, and Paullin as reporting that he had seen only fifteen cases of diabetic gangrene in 560 diabetic cases in Georgia. In the light
Since Silent Spring
Authors: Lester S. King
Journal: JAMA (1970)

As the word "pollution" becomes a rallying cry for reformers, the term "ecology" is beginning to etch itself into the American consciousness. We are learning slowly and painfully that nature shows complex interconnections and that disturbance in one area can bring unexpected but dire results in another. Rachel Carson made this point forcefully in her<i>Silent Spring</i>, a book which attacked the indiscriminate use of pesticides, especially those that persist and cumulate. Her book aroused vigorous controversy and was widely attacked, not only by spokesmen for the chemical industry but also by impartial scientists and not a few medical pundits. However, the validity of Miss Carson's main thesis has been amply vindicated in recent years, and a retrospective look at the critics and their criticisms makes us aware of the unflattering light in which they now stand revealed. Mr. Graham, a conservationist and editor of<i>Audubon</i>magazine, has written an