tbuckley/cabot-search huggingface dataset:
Epigenetic Silencing Mediated through Activated PI3K/AKT Signaling in Breast Cancer
Authors: Tao Zuo, Ta-Ming Liu, Xun Lan, Yu-I Weng, Rulong Shen, Fei Gu, Yi-Wen Huang, Sandya Liyanarachchi, Daniel E. Deatherage, Pei-Yin Hsu, Cenny Taslim, Bhuvaneswari Ramaswamy, Charles L. Shapiro, Huey-Jen L. Lin, Alfred S. L. Cheng, Victor X. Jin, Tim H.-M. Huang
Journal: Cancer Research (2011)

Abstract Trimethylation of histone 3 lysine 27 (H3K27me3) is a critical epigenetic mark for the maintenance of gene silencing. Additional accumulation of DNA methylation in target loci is thought to cooperatively support this epigenetic silencing during tumorigenesis. However, molecular mechanisms underlying the complex interplay between the two marks remain to be explored. Here we show that activation of PI3K/AKT signaling can be a trigger of this epigenetic processing at many downstream target genes. We also find that DNA methylation can be acquired at the same loci in cancer cells, thereby reinforcing permanent repression in those losing the H3K27me3 mark. Because of a link between PI3K/AKT signaling and epigenetic alterations, we conducted epigenetic therapies in conjunction with the signaling-targeted treatment. These combined treatments synergistically relieve gene silencing and suppress cancer cell growth in vitro and in xenografts. The new finding has important implications for improving targeted cancer therapies in the future. Cancer Res; 71(5); 1752–62. ©2011 AACR.
Effect of Rituximab in Patients With Leucine-Rich, Glioma-Inactivated 1 Antibody–Associated Encephalopathy
Authors: Sarosh R. Irani, Jeffrey M. Gelfand, Brianne M. Bettcher, Neel S. Singhal, Michael D. Geschwind
Journal: JAMA Neurology (2014)

<h3>Importance</h3> This observational study describes the efficacy and safety of rituximab in 5 patients with voltage-gated potassium channel (VGKC)–complex/leucine-rich, glioma-inactivated 1 (LGI1) antibody–associated encephalopathy. Rituximab is a monoclonal antibody that targets CD20 and is used to treat other neurologic and nonneurologic diseases. <h3>Observations</h3> This case series reports sequential seizure frequencies, modified Rankin Scale scores, and VGKC-complex antibody titers in 5 adult patients (median age, 65 years; range, 48-73 years) treated with rituximab. Median time from symptom onset to rituximab initiation was 414 days (range, 312-851 days). One patient showed a rapid clinical improvement after treatment with rituximab alone and experienced a rituximab-responsive clinical relapse. Another showed possible improvement on neuropsychometric memory indexes after rituximab therapy. In contrast, all patients showed robust responses to treatment with glucocorticoids, intravenous immunoglobulins, and/or plasma exchange at some point in their illness. Treatment with glucocorticoids—less so with intravenous immunoglobulins and plasma exchange—was associated with the most marked reductions in VGKC-complex antibodies. The only patient who did not receive glucocorticoids showed the poorest clinical and serologic responses. <h3>Conclusions and Relevance</h3> Rituximab was well tolerated in this predominantly older adult patient population and may be an effective option for some patients with LGI1 antibody–associated encephalopathy. Glucocorticoid therapy appears particularly efficacious. Earlier rituximab administration and randomized trials are required to formally assess efficacy.
Lymphatic Mapping and Sentinel Lymph Node Biopsy for Breast Cancer: Developments and Resolving Controversies
Authors: Henry M. Kuerer, Lisa A. Newman
Journal: Journal of Clinical Oncology (2005)

It has now been over 10 years since lymphatic mapping and sentinel lymph node (SLN) biopsy was first used in patients with breast cancer. Since the procedure was introduced, over 1,500 studies on SLN biopsy in breast cancer have been published in the cited world medical literature. Over 11,000 women have been enrolled in National Cancer Institute–sponsored SLN biopsy trials for breast cancer, the final results of which will not be available until several years from now. In the meantime, both the National Comprehensive Cancer Network treatment guidelines in the United States and the Saint Gallen International Consensus Conference on the treatment of breast cancer have now indicated that SLN biopsy is an acceptable alternative to axillary lymph node dissection in patients with clinically nodenegative breast cancer, provided that the SLN team has documented experience with this technique. Simply stated, although long-term follow-up data are not yet available from randomized trials comparing SLN biopsy with axillary lymph node dissection, SLN biopsy has become an acceptable alternative to routine level I and II axillary lymph node dissection for women with clinically node-negative early-stage breast cancer in the United States and in several other developed countries. However, despite a clear picture of increasing integration of SLN biopsy into standard diagnostic and therapeutic strategies for breast cancer, there are several clinical scenarios in which the utility of this technique has been questioned. This article will focus on current and resolving controversies associated with breast cancer lymphatic mapping and SLN biopsy.
Howell Pritchard Jones
Authors: R. P. Jones
Journal: BMJ (2013)

Inflammation constitutes an important component of host defense against pathogenic bacteria. This innate immune response is crucial for clearance of pathogens and survival of the host. However, unrestrained inflammatory reaction may result in systemic manifestations with dire consequences to the host. The extent of activation of the inflammatory response is tightly regulated through immunological and neural pathways. We have previously demonstrated that cholinergic stimulation, by administration of acetylcholinesterase inhibitors, confers enhanced protection in experimental animals orally infected with virulent <i>Salmonella typhymurium</i>. In this study, we investigated the mechanism by which AChE inhibition modulates the immune response to Salmonella infection. Enhanced host survival following oral infection correlated with significantly reduced bacterial dissemination to target organs, including livers and spleens. This protection was not due to increased gut motility or rapid bacterial clearance from the gastrointestinal tract. Moreover, protection was lost when the animals were infected systemically, suggesting that acetylcholine-mediated protective effect was mostly confined to gut mucosal tissue. <i>In vivo</i> imaging demonstrated more localized infection and delay in bacterial dissemination into systemic organs in mice pre-treated with AChE inhibitors. Morphological analysis of small intestine (ileum) showed that AChE inhibition induced degranulation of goblet cells and Paneth cells, two specialized secretory cells involved in innate immunity. Our findings demonstrate a crucial pathway between neural and immune systems that acts at the mucosal interface to protect the host against invading pathogens.
Mortality Data Analysis Using a Multiple-Cause Approach
Authors: Richard A. Goodman
Journal: JAMA (1982)

Death certificates are the primary source for information used to define general mortality patterns in the United States. Analyses of mortality data generally are restricted to one of the conditions listed on the certificate--the underlying cause of dealth. We review principles related to the use of mortality data and describe a study using mortality tapes ("multiple-cause tapes") that list all conditions recorded on dealth certificates. Using multiple-cause tapes, we found that the number of deaths associated with seven infectious diseases in 1968, 1969, and 1970 was from 24% (diphtheria) to 81% (rubella) greater than that officially reported. Multiple-cause tapes also permitted a review of the association of deaths attributed to measles and varicella and known complications of these diseases. these observations confirm the usefulness of multiple-cause tapes in analyzing mortality data and emphasize the importance of examining all conditions listed on the death certificate.
Dermatological aspects of the use of Cyclosporin A for prophylaxis of graft-versus-host disease
Authors: J.I. HARPER, J.R. KENDRA, S. DESAI, R.C.D. STAUGHTON, A.J. BARRETT, J.R. HOBBS
Journal: British Journal of Dermatology (1984)

Oral Cyclosporin A (CyA) was given for the prophylaxis of graft‐versus‐host disease (GVHD) to sixty‐seven patients receiving a bone marrow transplant, and was found to be extremely effective in reducing the severity of acute GVHD. Side‐effects of CyA included hypertrichosis, gum hypertrophy, and a rare but serious ‘capillary leak’ syndrome.
Expression of activated FcγRII discriminates between multiple granulocyte-priming phenotypes in peripheral blood of allergic asthmatic subjects
Authors: Deon Kanters, Willem ten Hove, Bart Luijk, Corneli van Aalst, René C. Schweizer, Jan-Willem J. Lammers, Hubert G.M. Leufkens, Jan A.M. Raaijmakers, Madelon Bracke, Leo Koenderman
Journal: Journal of Allergy and Clinical Immunology (2007)
US doctor may have killed 60
Authors: D. Woods
Journal: BMJ (2000)

A 45 year old doctor has been sentenced to life imprisonment in a federal court in New York for murdering three patients in a Long Island hospital seven years ago. But Dr Michael Swango, who is already in prison for possession of narcotics and fraud, is thought to have murdered many more patients—possibly as many as 60—and several colleagues.

His case has similarities to that of Harold Shipman, the English GP who was sent to prison in February for murdering 15 of his patients and who is suspected of killing many more (5 February, …
Hospital Care for Elderly Patients with Diseases of the Circulatory System
Authors: Geoffrey M. Anderson, Joseph P. Newhouse, Leslie L. Roos
Journal: New England Journal of Medicine (1989)

Abstract In an effort to determine how lower health care expenditures in Canada as compared with the United States translate into actual hospital services received, we examined discharge rates, lengths of stay, and the case-mix index (calculated from diagnosis-related group weights) for those 65 years of age and older hospitalized with cardiovascular disease in the United States and two Canadian provinces, Manitoba and Ontario, in 1981 and 1985. We expected that the effect of the prospective payment system might be reflected in changes between 1981 and 1985. Discharge rates for medical treatment of cardiovascular diseases were 2.9 percent higher in the United States than in Canada in 1981, but 1.8 percent lower in 1985; however, the case-mix index was 3.0 percent lower in 1981 and 4.8 percent higher in 1985. The case-mix Index for combined medical and surgical discharges was 5.0 percent lower in the United States in 1981, but 10.7 percent higher in 1985. U.S. surgical discharge rates were 20 percent lower In 1981, but 20 percent higher in 1985. Rates of coronary bypass surgery were much higher in the United States in both years, but increased rapidly in both countries, particularly among those 75 and older. Elderly Canadians appeared to have access to cardiovascular surgery, with the exception of coronary bypass surgery, and to other hospital care for cardiovascular disease similar to that of elderly people in the United States. (N Engl J Med 1989; 321:1443–8.)
Developmental Origins of Cancer
Authors: Kimberly J. Johnson, Nathan M. Springer, Anja-Katrin Bielinsky, David A. Largaespada, Julie A. Ross
Journal: Cancer Research (2009)

Laboratory and epidemiological studies on childhood and adult malignancy support a role for the developmental origins of cancer. The Developmental Origins of Cancer Symposium hosted by the University of Minnesota (February 28, 2009 to March 1, 2009) brought together individuals from diverse
Long-Term Trends in the Incidence of Heart Failure After Myocardial Infarction
Authors: Raghava S. Velagaleti, Michael J. Pencina, Joanne M. Murabito, Thomas J. Wang, Nisha I. Parikh, Ralph B. D'Agostino, Daniel Levy, William B. Kannel, Ramachandran S. Vasan
Journal: Circulation (2008)

Background— Although mortality after myocardial infarction (MI) has declined in the United States in recent decades, there have been few community-based investigations of the long-term trends in the incidence of heart failure after MI, and their results appear to be conflicting. Methods and Results— We evaluated 676 Framingham Heart Study participants between 45 and 85 years of age (mean age 67 years, 34% women) who developed a first MI between 1970 and 1999. We assessed the incidence rates of heart failure and of death without heart failure in each of 3 decades (1970 to 1979, 1980 to 1989, and 1990 to 1999). We estimated the multivariable-adjusted risk of events in the latter 2 decades, with the period 1970 to 1979 serving as the referent. The 30-day incidence of heart failure after MI rose from 10% in 1970 to 1979 to 23.1% in 1990 to 1999 ( P for trend 0.003), whereas 30-day mortality after MI declined from 12.2% (1970 to 1979) to 4.1% (1990 to 1999). The 5-year incidence of heart failure after MI rose from 27.6% in 1970 to 1979 to 31.9% in 1990 to 1999 ( P for trend 0.02), whereas 5-year mortality after MI declined from 41.1% (1970 to 1979) to 17.3% (1990 to 1999). In multivariable analyses, compared with the period 1970 to 1979, we observed higher 30-day (risk ratio 2.05, 95% confidence interval 1.25 to 3.36) and 5-year (risk ratio 1.74, 95% confidence interval 1.07 to 2.84) risks of heart failure in the decade 1990 to 1999. These trends were accompanied by lower 30-day (risk ratio 0.21, 95% confidence interval 0.09 to 0.47) and 5-year (risk ratio 0.31, 95% confidence interval 0.18 to 0.54) mortality rates in 1990 to 1999. Conclusions— In the present community-based sample, we observed an increase in the incidence of heart failure in recent decades that paralleled the decrease in mortality after MI.
Dissemination of ST131 and ST393 community-onset, ciprofloxacin-resistant Escherichia coli clones causing urinary tract infections in Korea
Authors: Mi Young Lee, Hyeon Jin Choi, Ji Young Choi, Minsuk Song, Yoosuk Song, Shin-Woo Kim, Hyun-Ha Chang, Sook-In Jung, Yeon-Sook Kim, Hyun Kyun Ki, Jun Seong Son, Ki Tae Kwon, Sang Taek Heo, Joon-Sup Yeom, Sang Yop Shin, Doo Ryeon Chung, Kyong Ran Peck, Jae-Hoon Song, Kwan Soo Ko
Journal: Journal of Infection (2009)
Fat and Cholesterol Regulator Identified
Authors: Tracy Hampton
Journal: JAMA (2006)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Proteinuria precedes podocyte abnormalities inLamb2-/- mice, implicating the glomerular basement membrane as an albumin barrier
Authors: G. Jarad
Journal: Journal of Clinical Investigation (2006)

Primary defects in either podocytes or the glomerular basement membrane (GBM) cause proteinuria, a fact that complicates defining the barrier to albumin. Laminin β2 (LAMB2) is a GBM component required for proper functioning of the glomerular filtration barrier. To investigate the GBM's role in glomerular filtration, we characterized GBM and overlying podocyte architecture in relation to development and progression of proteinuria in Lamb2–/– mice, which model Pierson syndrome, a rare congenital nephrotic syndrome. We found ectopic deposition of several laminins and mislocalization of anionic sites in the GBM, which together suggest that the Lamb2–/– GBM is severely disorganized, although it is ultrastructurally intact. Importantly, albuminuria was detectable shortly after birth and preceded podocyte foot process effacement and loss of slit diaphragms by at least 7 days. Expression and localization of slit diaphragm and foot process–associated proteins appeared normal at early stages. GBM permeability to the electron-dense tracer ferritin was dramatically elevated in Lamb2–/– mice, even before widespread foot process effacement. Increased ferritin permeability was not observed in nephrotic CD2-associated protein–null (Cd2ap–/–) mice, which have a primary podocyte defect. Together these data show that the GBM serves as a barrier to protein in vivo and that the glomerular slit diaphragm alone is not sufficient to prevent the passage of albumin into the urinary space.
Adiponectin Decreases Postprandially Following a Heat-Processed Meal in Individuals With Type 2 Diabetes
Authors: Alin Stirban, Monica Negrean, Bernd Stratmann, Christian Götting, Julia Salomon, Knut Kleesiek, Diethelm Tschoepe
Journal: Diabetes Care (2007)

Adiponectin regulates insulin sensitivity (1), reduces the expression of endothelial adhesion molecules (2), and has anti-inflammatory effects (3). Decreased adiponectin levels accompany obesity (4) and type 2 diabetes (5), promoting insulin resistance (5) and cardiovascular disease (6,7). Data on postprandial adiponectin regulation in different populations are controversial, with studies showing no effect (8–11), increases (12,13), or decreases (14,15). Advanced glycation end products (AGEs) (16) play a major role in the development of diabetes complications (17). We have shown that dietary AGEs acutely impair endothelial function (18,19), an effect counteracted by benfotiamine (20), a transketolase activator that blocks several hyperglycemia-induced pathways, including the formation of AGEs (21). AGEs might interact with adipocytes through AGE receptors (22) and induce cellular dysfunction via generation of reactive oxygen species (23), a pathway probably responsible for the AGE-induced downregulation of leptin secretion in vitro (24).

Our study aimed at investigating the effects of a high heat–processed meal with high AGE content (HAGE) and a low heat–processed meal with low AGE content (LAGE) on postprandial adiponectin concentration. We postulated a protective effect of benfotiamine.

Nineteen inpatients with type 2 diabetes (mean ± SEM age 55.2 ± 1.9 years; diabetes duration 7.3 ± 1.2 years; BMI 29.2 ± 0.8 kg/m2; A1C 8.8 ± 0.4%; 13 male and 6 female; 4 smokers and 15 nonsmokers; 15 on oral diabetes medication alone, 2 on oral diabetes medication plus insulin, and 2 …
Prevention of tuberculosis in HIV-1
Authors: Neal A Halsey, Jacqueline Coberly, Richard Chaisson
Journal: The Lancet (1998)

R Colebunders and E Florence (June 13, p 1813),1Colebunders R Florence E Isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection.Lancet. 1998; 351: 1813Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar question the proposed use of short-course rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infected, PPD positive people in developing countries. There is broad agreement that case-finding and directly observed therapy should be the foundation of tuberculosis control programmes in all countries. Nevertheless, there is increasing evidence that even with good treatment programmes, the incidence of tuberculosis is escalating because of HIV-1 infection.2Cantwell MF Binkin NJ Tuberculosis in sub-Saharan Africa: a regional assessment of the impact of the human immunodeficiency virus and National Control Programme quality.Tuberc Lung Dis. 1996; 77: 220-225Summary Full Text PDF PubMed Scopus (44) Google Scholar, 3Harries AD Mbewe LN Salaniponi FML et al.Tuberculosis programme changes and treatment outcomes in patients with smearpositive pulmonary tuberculosis in Blantyre, Malawi.Lancet. 1996; 347: 807-809Abstract PubMed Scopus (28) Google Scholar More can and should be done to prevent tuberculosis in high-risk individuals living in developing countries, especially HIV-1-infected people. The identification of shortcourse (about 2 months) regimens that effecively prevent tuberculosis in highrisk individuals is an important step in improving tuberculosis control. Concerns about development of resistance to isoniazid, rifampicin, or any other antituberculosis drug have been expressed and should be taken into consideration. In our trial, we found no acquired drug resistance and isoniazid chemoprophylaxis did not contribute to resistance. We agree that chemoprophylaxis of high-risk individuals should be undertaken only after active tuberculosis has been ruled out by the most practical method available, ideally a chest radiograph. Demonstration projects are needed to assess the practicality of implementing chemoprophylatic regimens on a wider scale and sources of funding need to be identified. Failure to expand tuberculosis control measures will ensure a continuation of the current, disastrous situation.
PEEP or No PEEP — Lung Recruitment May Be the Solution
Authors: Arthur S. Slutsky, Leonard D. Hudson
Journal: New England Journal of Medicine (2006)

The acute respiratory distress syndrome (ARDS) is characterized by inflammatory lung injury with alveolar flooding and abnormalities in surfactant function. ARDS (a subcategory of acute lung injury) is associated with the collapse of peripheral lung units, pulmonary infiltrates, stiff lungs, and hypoxemia.1 The syndrome is both common (with an incidence of about 80 cases per 100,000 population every year) and lethal (with a death rate of more than 38 percent) in a community population of patients with acute lung injury.2Patients with severe ARDS invariably require mechanical ventilation to decrease the work of breathing and to improve oxygen transport. An . . .