tbuckley/cabot-search huggingface dataset:
A self-adjuvanting multiepitope immunogen that induces a broadly cross-reactive antibody to hepatitis C virus
Authors: Joseph Torresi, Owen M. Stock, Alexandra E. Fischer, Lara Grollo, Heidi Drummer, Irene Boo, Weiguang Zeng, Linda Earnest‐Silveira, David C. Jackson
Journal: Hepatology (2007)

We describe a peptide-based strategy for HCV vaccine design that addresses the problem of variability in hypervariable region 1 (HVR1). Peptides representing antibody epitopes of HVR1 from genotype 1a were synthesized and incorporated into multideterminant immunogens that also included lipid moieties and helper T (Th) cell epitopes. Mice inoculated with these polyepitopes generated strong antibody responses. Antibody titers were highest in mice inoculated with polyepitope immunogens which contained the lipid moiety dipalmitoyl-S-glyceryl cysteine (Pam2Cys). Antisera were tested for their potential to neutralize HCV by 3 currently available assays. Antibodies elicited in mice by the polyepitope-based vaccine candidates were able to (1) bind to E2 expressed on the surface of E1/E2-transfected human embryonic kidney (HEK) 293T cells, (2) capture HCV of different genotypes (1, 2, and 3) from the serum of chronically infected humans in an immune capture RT-PCR assay and (3) inhibit HCVpp entry into Huh7 cells. Antibody present in the sera of patients chronically infected with HCV genotypes 1, 2, 3, and 4 also bound to the HVR1-based polyepitope. Conclusion: These results demonstrate the potential of self-adjuvanting epitope-based constructs in the development and delivery of cross-reactive immunogens that incorporate potential neutralizing epitopes present within the viral envelope of HCV. (HEPATOLOGY 2007;45:911–920.)
Treatment of Unruptured Abdominal Aortic Aneurysms
Authors: Irwin J. Schatz
Journal: JAMA (1970)

<h3>To the Editor.—</h3> Drs. Baker and Roberts (<b>212</b>:445, 1970) state "... these results (of resection of unruptured abdominal aortic aneurysms) appeared to show a nearly doubled life expectancy of patients subjected to operation when compared to those not operated upon." Their final paragraph contains the statement "... the mere presence of such a lesion (abdominal aortic aneurysm) is the indication for its removal in the large majority of patients." The data they present in no way support these conclusions. Indeed in their communication they say "... there is no comparable series of untreated patients from this institution..." and "... to have meaning, these long-term survival figures must be compared to those available for patients with aneurysms but not operated upon. Such a comparison is difficult as exactly comparable series are not available..." Thus, Drs. Baker and Roberts seem to accept that results derived from comparing
Efficacy of activation of Peroxisome Proliferative-Activated Receptors (PPAR)-a on vasular remodeling after coronary angioplasty: possible role of endothelial dysfunction and collagen accumulation
Authors: Katsumi Miyauchi, Takeshi Kurata, Takayuki Yokoyama, Yoshinori Akimoto, Kouichiro Aihara, Kazunori Shimada, Hitoshi Satoh, Hiroyuki Daida
Journal: Journal of the American College of Cardiology (2002)
Graft-versus-Host Disease
Authors: James L.M. Ferrara, H. Joachim Deeg
Journal: New England Journal of Medicine (1991)

DURING the 1980s the number of allogeneic bone marrow transplantations performed worldwide increased exponentially. In 1990 more than 4000 allogeneic transplantations were estimated to have been completed. This dramatic increase has been stimulated by the demonstration that bone marrow transplantation is an important therapeutic option for many patients with leukemia or lymphoma. In addition, the establishment of international marrow-donor registries has made HLA phenotypically matched marrow from unrelated donors available to patients who lack a suitable related donor. These developments have focused attention on the immunologic aspects of allogeneic transplantation and its chief complication, graft-versus-host disease (GVHD).Definition and Cause . . .
A view from the beach
Authors: K. Patel
Journal: BMJ (2009)

I’m on honeymoon at the moment, sitting on an idyllic beach on an island off the coast of Thailand. Which, as I am sure you can imagine, makes writing my next column a bit more taxing than usual.

What do you suppose my greatest fear is (aside from the constant war of attrition I am losing with the local mosquitoes)? Being robbed? No—in fact it seems safer than parts of London here. Losing my luggage? Again, not too much of a concern. The bags are carried by hand from the aircraft …
THE TREATMENT OF SALPINGO-OVARITIS BY ELECTRICITY.
Authors: GEORGE APOSTOLI
Journal: JAMA (1889)

The electrical treatment of fibroma which I originated has made great strides despite the railings of charlatans and incompetent persons; it is not necessary to refer to this subject again, because it is a child that will grow of itself, and is amply able to take care of itself. To-day I invite your attention to a subject of equal interest, I mean the treatment by electricity of salpingo-ovaritis, and I sincerely hope that it may have the same useful future, more restricted perhaps, because at present it is restricted to a certain number of cases, but in any case worthy of your consideration. Salpingo-ovaritis is a disease which has long been recognized, but under names which I have changed very often:<i>Phlegmon, pelvic-peri-tonitis, lymphangitis, adeno-lymphangitis, cellulitis, peri-metritis, para-metritis, peri-uterine, phlegmasia, etc.;</i>all of these titles being used to picture a disease originating in the lymphatics, in the cellular tissue, or
New minister to tackle Poland's healthcare crisis
Authors: Jane Burgermeister
Journal: BMJ (2004)

Doctors in Poland have welcomed the appointment on 15 July of Marek Balicki as the new health minister after the surprise resignation of his predecessor, Marian Czakanski, who had been in office for only one month.

Mr Balicki, a Social Democrat who briefly served as health minister at the beginning of 2003, faces an uphill task to win support for new legislation to reform the country's health service from the country's fragmented parliament by August.

“I think that Marek Balicki offers a ray of hope, …
AMA's Science Reporters Conference Focuses on Contraception and Prevention of Premature Birth
Authors: Andrew A. Skolnick
Journal: JAMA (1996)

THE 15th Annual Science Reporters Conference of the American Medical Association (AMA), held in San Francisco, Calif, focused in large part on women's health issues. One morning of the 3-day conference was devoted to presentations that were simulcast via satellite to news reporters in New York, NY. Two of the 3 presentations concerned what patients need to know about birth control options; the third addressed strategies that can help reduce health problems and costs associated with premature birth. Before the investigators spoke, Timothy T. Flaherty, MD, a member of the AMA's Board of Trustees, introduced the Association's new consumer book,<i>American Medical Association Complete Guide to Women's Health</i>(New York, NY: Random House Inc; 1996), edited by Ramona I. Slupik, MD. More than 30 specialists contributed to making the guide the most thorough and up-to-date source of information on health concerns of women of all ages, Flaherty said. <h3>Preventing Unwanted</h3>
A mouse model of pemphigus vulgaris by adoptive transfer of naive splenocytes from desmoglein 3 knockout mice
Authors: M. Aoki-Ota, K. Tsunoda, T. Ota, T. Iwasaki, S. Koyasu, M. Amagai, T. Nishikawa
Journal: British Journal of Dermatology (2004)

Background Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by antidesmoglein3 (anti-Dsg3) IgG autoantibodies. Recently, we developed a PV mouse model by adoptive transfer of splenocytes from recombinant Dsg3-immunized Dsg3–/– mice to Rag2–/– immunodeficient mice that expressed Dsg3. Objectives We determined whether the adoptive transfer of naive splenocytes from nonimmunized Dsg3–/– mice induces the anti-Dsg3 IgG production and the PV phenoytpe in recipient mice. Methods We adoptively transferred naive Dsg3–/– splenocytes into Rag2–/– mice and compared their PV phenoytpe with those mice receiving immunized Dsg3–/– splenocytes. The numbers of splenocytes and their subpopulations required for anti-Dsg3 IgG production were examined. Results Mice that received naive Dsg3–/– splenocytes produced anti-Dsg3 IgG, which bound to keratinocyte cell surfaces in vivo, and developed the PV phenotype, including oral erosions with suprabasilar acantholysis. Antibody production and the appearance of the PV phenotype were delayed by approximately 2 weeks in mice that received naive splenocytes compared with mice that received immunized splenocytes. However, once the PV phenotypes developed, there were no apparent differences in disease severity between the two models. Interestingly, the anti-Dsg3 IgG titres were significantly lower in mice that received naive splenocytes than in mice that received immunized splenocytes, suggesting that the former antibodies were more potent than the latter. The frequency of anti-Dsg3 IgG production depended on the number of transferred naive splenocytes. Both CD4+ T cells and B220+ B cells from naive Dsg3–/– mice were essential for the production of anti-Dsg3 IgG antibodies. Conclusions Dsg3-specific naive lymphocytes in Dsg3–/– mice can be primed and activated by the endogenous Dsg3 in recipient mice to produce pathogenic anti-Dsg3 IgG without active immunization. This approach using naive lymphocytes provides a unique model to dissect immunological mechanisms of tolerance against peripheral autoimmune targets.
GW25-e3088 VO 2 /kg peak, VE/VCO 2 nadir and VE/VCO 2 slope of Cardiopulmonary Exercise Testing Among Different Chinese CAD-patient Groups
Authors: Wang Yafei, Liang Qi, Zhang Guolin, Liu Zhi, Guo Lan
Journal: Journal of the American College of Cardiology (2014)
Overexpression of the Circadian Clock Gene <i>Bmal1</i> Increases Sensitivity to Oxaliplatin in Colorectal Cancer
Authors: Zhao-lei Zeng, Hui-yan Luo, Jing Yang, Wen-jing Wu, Dong-liang Chen, Peng Huang, Rui-hua Xu
Journal: Clinical Cancer Research (2013)

The circadian clock gene Bmal1 is involved in cancer cell proliferation and DNA damage sensitivity. The aim of this study was to explore the effect of Bmal1 on oxaliplatin sensitivity and to determine its clinical significance in colorectal cancer.Three colorectal cancer cell lines, HCT116, THC8307 and HT29, were used. The Bmal1-mediated control of colorectal cancer cell proliferation was tested in vitro and in vivo. MTT and colony formation assays were performed to determine the sensitivity of colorectal cancer cells to oxaliplatin. Flow cytometry was used to examine changes in the cell-cycle distribution and apoptosis rate. Proteins expressed downstream of Bmal1 upon its overexpression were determined by Western blotting. Immunohistochemistry was used to analyze Bmal1 expression in 82 archived colorectal cancer tumors from patients treated with oxaliplatin-based regimens.Bmal1 overexpression inhibited colorectal cancer cell proliferation and increased colorectal cancer sensitivity to oxaliplatin in three colorectal cancer cell lines and HCT116 cells model in vivo. Furthermore, the overall survival of patients with colorectal cancer with high Bmal1 levels in their primary tumors was significantly longer than that of patients with low Bmal1 levels (27 vs. 19 months; P = 0.043). The progression-free survival of patients with high Bmal1 expression was also significantly longer than that of patients with low Bmal1 expression (11 vs. 5 months; P = 0.015). Mechanistically, the effect of Bmal1 was associated with its ability to regulate G2-M arrest by activating the ATM pathway.Bmal1 shows the potential as a novel prognostic biomarker and may represent a new therapeutic target in colorectal cancer.
Defining the In Vivo Phenotype of Artemisinin-Resistant Falciparum Malaria: A Modelling Approach
Authors: Lisa J. White, Jennifer A. Flegg, Aung Pyae Phyo, Ja Hser Wiladpai-ngern, Delia Bethell, Christopher Plowe, Tim Anderson, Standwell Nkhoma, Shalini Nair, Rupam Tripura, Kasia Stepniewska, Wirichada Pan-Ngum, Kamolrat Silamut, Ben S. Cooper, Yoel Lubell, Elizabeth A. Ashley, Chea Nguon, François Nosten, Nicholas J. White, Arjen M. Dondorp
Journal: PLoS Medicine (2015)

Background Artemisinin-resistant falciparum malaria has emerged in Southeast Asia, posing a major threat to malaria control. It is characterised by delayed asexual-stage parasite clearance, which is the reference comparator for the molecular marker 'Kelch 13' and in vitro sensitivity tests. However, current cut-off values denoting slow clearance based on the proportion of individuals remaining parasitaemic on the third day of treatment ('day-3'), or on peripheral blood parasite half-life, are not well supported. We here explore the parasite clearance distributions in an area of artemisinin resistance with the aim refining the in vivo phenotypic definitions. Methods and Findings Data from 1,518 patients on the Thai-Myanmar and Thai-Cambodian borders with parasite half-life assessments after artesunate treatment were analysed. Half-lives followed a bimodal distribution. A statistical approach was developed to infer the characteristics of the component distributions and their relative contribution to the composite mixture. A model representing two parasite subpopulations with geometric mean (IQR) parasite half-lives of 3.0 (2.4-3.9) hours and 6.50 (5.7-7.4) hours was consistent with the data. For individual patients, the parasite half-life provided a predicted likelihood of an artemisinin-resistant infection which depends on the population prevalence of resistance in that area. Consequently, a half-life where the probability is 0.5 varied between 3.5 and 5.5 hours. Using this model, the current 'day-3' cut-off value of 10% predicts the potential presence of artemisinin-resistant infections in most but not all scenarios. These findings are relevant to the low-transmission setting of Southeast Asia. Generalisation to a high transmission setting as in regions of Sub-Saharan Africa will need additional evaluation. Conclusions Characterisation of overlapping distributions of parasite half-lives provides quantitative insight into the relationship between parasite clearance and artemisinin resistance, as well as the predictive value of the 10% cut-off in 'day-3' parasitaemia. The findings are important for the interpretation of in vitro sensitivity tests and molecular markers for artemisinin resistance and for contextualising the 'day 3' threshold to account for initial parasitaemia and sample size.
Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth
Authors: Thanh U. Barbie, Gabriela Alexe, Amir R. Aref, Shunqiang Li, Zehua Zhu, Xiuli Zhang, Yu Imamura, Tran C. Thai, Ying Huang, Michaela Bowden, John Herndon, Travis J. Cohoon, Timothy Fleming, Pablo Tamayo, Jill P. Mesirov, Shuji Ogino, Kwok-Kin Wong, Matthew J. Ellis, William C. Hahn, David A. Barbie, William E. Gillanders
Journal: Journal of Clinical Investigation (2014)

Triple-negative breast cancers (TNBCs) are a heterogeneous set of cancers that are defined by the absence of hormone receptor expression and HER2 amplification. Here, we found that inducible IκB kinase-related (IKK-related) kinase IKBKE expression and JAK/STAT pathway activation compose a cytokine signaling network in the immune-activated subset of TNBC. We found that treatment of cultured IKBKE-driven breast cancer cells with CYT387, a potent inhibitor of TBK1/IKBKE and JAK signaling, impairs proliferation, while inhibition of JAK alone does not. CYT387 treatment inhibited activation of both NF-κB and STAT and disrupted expression of the protumorigenic cytokines CCL5 and IL-6 in these IKBKE-driven breast cancer cells. Moreover, in 3D culture models, the addition of CCL5 and IL-6 to the media not only promoted tumor spheroid dispersal but also stimulated proliferation and migration of endothelial cells. Interruption of cytokine signaling by CYT387 in vivo impaired the growth of an IKBKE-driven TNBC cell line and patient-derived xenografts (PDXs). A combination of CYT387 therapy with a MEK inhibitor was particularly effective, abrogating tumor growth and angiogenesis in an aggressive PDX model of TNBC. Together, these findings reveal that IKBKE-associated cytokine signaling promotes tumorigenicity of immune-driven TNBC and identify a potential therapeutic strategy using clinically available compounds.
Biphasic nature of gastric emptying.
Authors: J A Siegel, J L Urbain, L P Adler, N D Charkes, A H Maurer, B Krevsky, L C Knight, R S Fisher, L S Malmud
Journal: Gut (1988)

The existence of a lag phase during the gastric emptying of solid foods is controversial. It has been hypothesised that among other early events, the stomach requires a period of time to process solid food to particles small enough to be handled as a liquid. At present no standardised curve fitting techniques exist for the characterisation and quantification of the lag phase or the emptying rate of solids and liquids. We have evaluated the ability of a modified power exponential function to define the emptying parameters of two different solid meals. Dual labelled meals were administered to 24 normal volunteers. The subjects received meals consisting of either Tc-99m in vivo labelled chicken liver or Tc-99m-egg, which have different densities, and In-111-DTPA in water. The emptying curves were biphasic in nature. For solids, this represented an initial delay in emptying or lag phase followed by an equilibrium emptying phase characterised by a constant rate of emptying. The curves were analysed using a modified power exponential function of the form y(t) = 1-(1-e-kt)beta, where y(t) is the fractional meal retention at time t, k is the gastric emptying rate in min-1, and beta is the extrapolated y-intercept from the terminal portion of the curve. The length of the lag phase and half-emptying time increased with solid food density (31 +/- 8 min and 77.6 +/- 11.2 min for egg and 62 +/- 16 min and 94.1 +/- 14.2 min for chicken liver, respectively). After the lag phase, both solids had similar emptying rates, and these rates were identical to those of the liquids. In vitro experiments indicated that the egg meal disintegrated much more rapidly than the chicken liver under mechanical agitation in gastric juice, lending further support to the hypothesis that the initial lag in emptying of solid food is due to the processing of food into particles small enough to pass the pylorus. We conclude that the modified power exponential model permits characterisation of the biphasic nature of gastric emptying allowing for quantification of the lag phase and the rate of emptying for both solids and liquids.
IgE in stools as indicator of food sensitization
Authors: F. André, C. André, L. Colin, S. Cavagna
Journal: Allergy (1995)

The fragment of the Fc segment of IgE resistant to proteolytic enzymes was determined by a radioimmunologic method in fecal extracts from several groups of patients. IgEs remained undetectable in the 95 healthy subjects studied. IgEs were detected in 16/27 carriers of intestinal parasites (60%), with a mean of 92.4 IU/g dry weight. IgEs were also detected in 236/312 food‐sensitization patients, with the sensitizing foodstuffs being identified by searching for the specific IgEs in circulation (75%), with a mean of 63.9 IU/g dry weight. The simultaneous determination of alpha‐ 1‐antitrypsin in fecal extracts arid in sera from 21 control subjects and 21 food‐sensitization carriers demonstrated that extravasation of plasma proteins into the gut lumen cannot be responsible for the presence of IgE in stools. Testing for IgE in stools therefore appears to be a simple and economical means of identifying patients without parasites who present with food sensitization.
Familial juvenile-onset diabetes.
Authors: P G Nelson, L J Arthur, K J Gurling, D R Gamble, K W Taylor
Journal: BMJ (1977)

On three separate occasions he has been admitted to hospital as an emergency semicomatose in atrial fibrillation confirmed electrocardiographically.Semicoma lasted 1-4 hours, drowsiness up to 20 hours, followed by headache and spontaneous reversion to sinus rhythm.On other occasions he has had similar attacks at home but neither he nor his wife have noticed his pulse irregular at any time.Apart from mild high tone deafness, the results of investigations including skull x-ray films, lumbar puncture, left carotid angiogram, chest x-ray film, and protein bound iodine concentration were all normal as was his ECG between attacks.An EEG was reported as showing right-sided slow and sharp waves over the parietal occipital areas.Treatment at intervals with digoxin, phenytoin, clonidine, amitriptyline, and psychotherapy did not alter the frequency or the nature of the attacks.
Women, Health, and Development: An American Perspective
Authors: HELEN L. SMITS
Journal: Annals of Internal Medicine (1986)

Editorials1 February 1986Women, Health, and Development: An American PerspectiveHELEN L. SMITS, M.D.HELEN L. SMITS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-104-2-263 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe director-general of the World Health Organization (WHO) has just issued Women, Health and Development (1). This brief, clear document, published to mark the end of the United Nations Decade for Women, contains an important message for American physicians.The report provides a stark reminder of the basic biological fact that control over fertility is essential to womens' ability to function in society, to their health, and to the health of society as a whole. The ability to plan pregnancies is as important to the mother and field laborer in rural Africa as it is to the woman who wishes...References1. . Women, Health and Development: A Report by the Director-General. Geneva, Switzerland: World Health Organization; 1985. Google Scholar2. MUNDINGER M. Health service funding cuts and the declining health of the poor. N Engl J Med. 1985;313:44-7. CrossrefMedlineGoogle Scholar3. IGLEHART J. Medical care of the poor—a growing problem. N Engl J Med. 1985;313:59-63. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University of Connecticut Health Center Farmington, Connecticut PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByWhen becoming pregnant is a crime 1 February 1986Volume 104, Issue 2Page: 263-264KeywordsGlobal healthObstetrics and gynecologyPregnancy Issue Published: 1 February 1986 PDF DownloadLoading ...