tbuckley/cabot-search huggingface dataset:
RANTES Induces Nasal Mucosal Inflammation Rich in Eosinophils, Basophils, and Lymphocytes<i>In Vivo</i>
Authors: PIOTR KUNA, RAFEUL ALAM, URSZULA RUTA, PAWEL GORSKI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

RANTES is a CC chemokine that causes chemotaxis of eosinophils, basophils, and lymphocytes in vitro. The objective of this study was to investigate the effect of RANTES on the influx of inflammatory cells into the nasal mucosa of 12 allergic patients. In the first phase, each patient was challenged with RANTES or diluent on two subsequent days. RANTES caused a significant (p < 0.05) influx of eosinophils as compared with the diluent. The number of eosinophils were 5,548 ± 1,532/ml and 462 ± 206/ml after RANTES and diluent challenge, respectively, at the peak of the response at 2 h. There was also a significant influx of metachromatic cells and lymphocytes, but not monocytes, neutrophils, or epithelial cells after RANTES challenge. In the second phase, the patients were first challenged with an allergen and 24 h later, challenged with RANTES or diluent. In the allergen-primed mucosa RANTES induced a significantly higher influx of eosinophils, basophils, and lymphocytes. Further, RANTES caused migration of monocytes and neutrophils, and shedding of epithelial cells. The influx of the inflammatory cells was associated with symptoms of rhinitis. We conclude that RANTES induces a clinically symptomatic inflammatory response in vivo by causing chemotaxis of eosinophils, basophils, and mononuclear cells.
Increasing global obesity to US level equates to an extra half a billion people in food energy demand
Authors: S. Mayor
Journal: BMJ (2012)

Growing levels of overweight and obesity could have the same implications for world food energy demands as an extra half a billion people living on the earth if all countries reach the current fatness profile of the United States, warns a modelling study published this week.1

People’s weight, not just population size, should be taken into account when planning how to deal with increasing pressure on the planet’s dwindling resources, say the researchers.

“Everyone accepts that population growth threatens global environmental sustainability. Our study shows that population fatness is also a major threat,” said the lead author, Ian Roberts, professor of epidemiology and public health at …
Immunosuppression in Melanoma Immunotherapy: Potential Opportunities for Intervention
Authors: Gregory Lizée, Laszlo G. Radvanyi, Willem W. Overwijk, Patrick Hwu
Journal: Clinical Cancer Research (2006)

Abstract Although melanomas are substantially more immunogenic than other tumors, current immunotherapeutic approaches for melanoma patients have met with only limited success. Although melanoma-specific CD8+ T-cell responses can often be generated in patients naturally or through vaccination regimens, tumors frequently continue to grow unabated, suggesting that tumor-specific immune responses may be actively dampened in vivo. Research over the past decade has brought to light several mechanisms used by melanomas and other tumors to suppress tumor-specific immune responses. These include the presence of regulatory immune cells within the tumor microenvironment and draining lymph nodes that serve to shut down effector T-cell function. In addition, melanoma tumors themselves express a number of soluble and membrane-bound molecules that are responsible for inhibiting activated immune cells. The identification of these suppressive mechanisms has provided significant opportunities for designing novel therapeutic interventions that could augment current vaccination and adoptive transfer approaches for treatment of melanoma.
Pneumocystis carinii Pneumonia in a Family
Authors: James M. Watanabe
Journal: JAMA (1965)

PLASMA-CELL PNEUMONIA due to infection with<i>Pneumocystis carinii</i>is commonly seen in Europe but has been comparatively rare in North America. Recently, an increasingly large number of cases have been reported in the United States and Canada. Many cases have been quite sporadic; however, there are a few areas in which large numbers of cases have been seen—namely, North Carolina<sup>1</sup>and Montreal.<sup>2</sup>The disease has occurred mainly in premature or debilitated infants. It has been reported in epidemic form in nurseries for the premature; however, isolated cases are the rule. In a few instances, the disease has occurred in siblings but these instances were associated with hypogammaglobulinemia<sup>3</sup>or other serious diseases. Most adult cases<sup>4</sup>were associated with chronic or fatal diseases, such as cancers, cytomegalic-inclusion disease, collagen diseases. No coexisting disease could be found in two cases.<sup>5,6</sup> <h3>Report of Cases</h3> The following concerns a family
Acetylation pharmacogenetics. The slow acetylator phenotype is caused by decreased or absent arylamine N-acetyltransferase in human liver.
Authors: D M Grant, K Mörike, M Eichelbaum, U A Meyer
Journal: Journal of Clinical Investigation (1990)

The biochemical basis underlying the genetic polymorphism of drug N-acetylation was investigated using a combination of in vivo and in vitro assays for arylamine N-acetyltransferase (NAT) activity and content in human liver. The acetylator phenotype of 26 surgical patients was determined using caffeine as an innocuous probe drug by measurement of the 5-acetyl-amino-6-formylamino-3-methyluracil to 1-methylxanthine molar ratio in urine. Liver wedge biopsies from these patients and livers from 24 organ donors were then used for measurement of N-acetyltransferase activity with the substrate sulfamethazine and for quantitation of immunoreactive N-acetyl-transferase protein. In vivo (caffeine metabolites in urine) and in vitro (sulfamethazine acetylation) measures of N-acetyl-transferase activity correlated very highly (r = 0.98). Moreover, in all subjects tested, slow acetylation both in vivo and in vitro was associated with a decrease in the quantity of immunodetectable N-acetyltransferase protein in liver cytosol relative to that seen in cytosols from rapid acetylator livers. Two kinetically distinct enzyme activities, designated NAT-1 and NAT-2, were partially purified from low- and high-activity livers and their relationship to acetylator status was determined. Low acetylation capacity was related to decreases in the liver content of both of these immunologically related proteins. The results demonstrate that genetically defective arylamine N-acetylation is due to a parallel decrease in the quantity of two structurally and functionally similar acetylating enzymes.
Lung Cells in Disease
Authors: Valentin T. Popa
Journal: JAMA (1977)

The mammalian lung contains more than 40 different types of cells, but their biology has never been presented and discussed in an ad hoc meeting. This meeting has produced a fascinating book, which shows the importance of the multidisciplinary approach in lung research and the increasing need for information in lung biology. The list of participants reads like an excerpt from<i>Who's Who in the Biology of the Lung Cells</i>. There are three sections: "Cells in Normal Lung," "Mechanisms of Lung Disease," and "Impact on Lung Disease Research." The two excellent papers of the last section discuss the clinical implications of the progress made in lung biology. The first and second sections review recent personal work on the anatomy, biochemistry, pharmacology, and immunology of the lung cells. The highly specialized technical information is conveyed in a rather simple, direct fashion, making the book both intelligible and enjoyable. The personal results
Interaction of factor VIII antigen in hemophilic plasmas with human antibodies to factor VIII.
Authors: T S Zimmerman, L de la Pointe, T S Edgington
Journal: Journal of Clinical Investigation (1977)

By utilizing a simple modification of previous immunological assays, we have demonstrated that most, if not all, hemophilic plasmas contain antigen reactive with human antibodies directed against Factor VIII procoagulant activity (VIIIc). Antibodies developing in a nonhemophiliac patient and in a hemophiliac patient gave similar results. The VIIIc antigen so identified was removed from hemophilic plasmas with immobilized rabbit antibody which reacted with normal VIIIc and von Willebrand's disease antigen. These data suggest that there are greater antigenic similarities between normal and hemophilic Factor VIII than previously thought.
Relationship between Radiation Exposure and Risk of Second Primary Cancers among Atomic Bomb Survivors
Authors: Christopher I. Li, Nobuo Nishi, Jean A. McDougall, Erin O. Semmens, Hiromi Sugiyama, Midori Soda, Ritsu Sakata, Mikiko Hayashi, Fumiyoshi Kasagi, Akihiko Suyama, Kiyohiko Mabuchi, Scott Davis, Kazunori Kodama, Kenneth J. Kopecky
Journal: Cancer Research (2010)

Abstract Radiation exposure is related to risk of numerous types of cancer, but relatively little is known about its effect on risk of multiple primary cancers. Using follow-up data through 2002 from 77,752 Japanese atomic bomb survivors, we identified 14,048 participants diagnosed with a first primary cancer, of whom 1,088 were diagnosed with a second primary cancer. Relationships between radiation exposure and risks of first and second primary cancers were quantified using Poisson regression. There was a similar linear dose-response relationship between radiation exposure and risks of both first and second primary solid tumors [excess relative risk (ERR)/Gy = 0.65; 95% confidence interval (CI), 0.57–0.74 and ERR/Gy = 0.56; 95% CI, 0.33–0.80, respectively] and risk of both first and second primary leukemias (ERR/Gy = 2.65; 95% CI, 1.78–3.78 and ERR/Gy = 3.65; 95% CI, 0.96–10.70, respectively). Background incidence rates were higher for second solid cancers, compared with first solid cancers, until about age 70 years for men and 80 years for women (P &amp;lt; 0.0001), but radiation-related ERRs did not differ between first and second primary solid cancers (P = 0.70). Radiation dose was most strongly related to risk of solid tumors that are radiation-sensitive including second primary lung, colon, female breast, thyroid, and bladder cancers. Radiation exposure confers equally high relative risks of second primary cancers as first primary cancers. Radiation is a potent carcinogen and those with substantial exposures who are diagnosed with a first primary cancer should be carefully screened for second primary cancers, particularly for cancers that are radiation-sensitive. Cancer Res; 70(18); 7187–98. ©2010 AACR.
Antibody Levels and Protection after Hepatitis B Vaccination: Results of a 15-Year Follow-up
Authors: Brian J. McMahon, Dana L. Bruden, Kenneth M. Petersen, Lisa R. Bulkow, Alan J. Parkinson, Omana Nainan, Marina Khristova, Carolyn Zanis, Helen Peters, Harold S. Margolis
Journal: Annals of Internal Medicine (2005)

Background: The duration of protection afforded by hepatitis B vaccination is unknown. Objective: To determine antibody persistence and protection from hepatitis B virus (HBV) infection. Design: Prospective cohort study. Setting: 15 villages in southwest Alaska. Participants: 1578 Alaska Natives vaccinated at age 6 months or older. Intervention: During 1981–1982, participants received 3 doses of plasma-derived hepatitis B vaccine. This cohort was followed annually over the first 11 years, and 841 (53%) persons were tested at 15 years. Measurements: Antibody to hepatitis B surface antigen (anti-HBs), markers of HBV infection, and testing to identify HBV variants. Results: Levels of anti-HBs in the cohort decreased from a geometric mean concentration of 822 mIU/mL after vaccination to 27 mIU/mL at 15 years. Initial anti-HBs level, older age at vaccination, and male sex were associated with persistence of higher anti-HBs levels at 15 years when analyzed by a longitudinal linear mixed model. After adjustment for initial anti-HBs level and sex, those vaccinated at age 6 months to 4 years had the lowest anti-HBs level at 15 years. Asymptomatic breakthrough infections were detected in 16 participants and occurred more frequently in persons who did not respond to vaccination than those who responded (P = 0.01). Among infected persons with viremia, 2 were infected with wild-type HBV and 4 had HBV surface glycoprotein variants, generally accompanied by wild-type HBV. Limitations: The loss of participants to follow-up at 15 years was 47%. However, characteristics of persons tested were similar to those of persons lost to follow-up. Conclusions: Hepatitis B vaccination strongly protected against infection for at least 15 years in all age groups. Antibody levels decreased the most among persons immunized at 4 years of age or younger.
Federal Health Programs: Problems and Prospects
Authors: Bruce Stuart
Journal: JAMA (1981)

Given the obvious importance of the federal government in the financing, delivery, and regulation of health care, it is surprising that there are not more books on the subject. While there is no shortage of material on specific federal programs such as Medicare and Medicaid, there is no single work that covers the gamut of federal health policies and programs. This is a tall order to be sure, but one that Altman and Sapolsky set for themselves in the preface to this volume. The book derives from a project undertaken by the Boston-based University Health Policy Consortium for the Federal Trade Commission. The project was designed to explore briefly the economic impact of all federal health programs and to study nine programs in depth. The published results include a 16-page appendix listing some 92 government programs by function, and 12 chapters dealing with specific programs and issues. In some ways
Abstract ES8-2: Breast Cancer Stroma: A Predictor of Clinical Outcome and Tumour Heterogeneity
Authors: N Bertos, G Finak, R Lesurf, SM Saleh, H Zhao, M Souleimanova, S Meterrisian, A Omeroglu, M Hallett, M Park
Journal: Cancer Research (2012)

Abstract Breast cancer heterogeneity is one of the principal obstacles both to predicting outcome and to determining an effective course of treatment for this disease. Individual cases demonstrate heterogeneity at multiple levels, including those parameters assessed by studies of gene expression, chromosomal aberrations, and classical and immuno-pathology. Although genomic technologies have been used to gain a better understanding of the impact of gene expression heterogeneity on breast cancer outcome by identifying gene expression signatures associated with clinical outcome, histopathological breast cancer subtypes, and a variety of cancer–related pathways and processes, relatively little is known about the effects of heterogeneity in the tumor microenvironment. We have addressed changes in stroma by analyzing changes in gene expression in stromal tissue associated with breast tumors when compared to normal breast tissue. We have integrated gene expression data from laser capture microdissected breast tumor stroma with matched normal stroma. Using this approach we have identified that the microenvironment of a breast tumor can be classified into one of six distinct molecular phenotypes exhibiting distinct biological functions and carrying prognostic information independent of existing therapeutic biomarkers and tumor subtypes. A trained predictor of 23 genes was developed and contains new information to stratify breast cancer subtypes. This is independent of clinical parameters and published predictors of outcome and identifies patients with poor outcome in multiple breast cancer expression data generated using using whole tissue. The stromal predictor selects poor outcome patients from multiple clinical subtypes of breast cancer and contains genes representing distinct biological features, including differential immune response, angiogenic response, as well as a hypoxic response. Elements of this signature are present in murine models of breast cancer. These results highlight the complex relationship between the tumor and its microenvironment, and underline the role that the stroma plays in tumor progression. These results demonstrate an important role for the tumor microenvironment in defining breast cancer heterogeneity, with a consequent impact upon clinical outcome. Novel therapies could be targeted at the processes that define the stroma classes, suggesting new avenues for the development of individualized treatment regimens. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES8-2.
A CASE OF NEURITIS SIMULATING PROGRESSIVE MUSCULAR ATROPHY ASSOCIATED WITH NYSTAGMUS AND INCREASED KNEE JERKS.
Authors: Harold N Moyer
Journal: JAMA (1894)

The following singular grouping of symptoms came under our observation a short time since, and we deem it worthy of report because we have not seen such described in the literature nor has a similar case ever come under our observation: A young woman 21 years of age presented herself at the clinic for nervous diseases of Rush Medical College,complaining of a progressive loss of strength and wasting of the hands and arms. She stated that the trouble had come on four years before. There had been no injury or serious sickness. At the time her occupation, that of a servant, required her to have her hands frequently in cold water. At first there was much pain in the hands, which would dart up the forearm; associated with this condition was numbness and tingling. After a time she noticed a progressive loss of strength, and still later that the hands
Use of Child Booster Seats in Motor Vehicles Following a Community Campaign
Authors: Beth E. Ebel, Thomas D. Koepsell, Elizabeth E. Bennett, Frederick P. Rivara
Journal: JAMA (2003)

Once children have outgrown car seats, booster seats protect from injury better than lap and shoulder belts alone. However, the majority of children aged 4 to 8 years use only an adult seat belt.To evaluate the effectiveness of a multifaceted community booster seat campaign in increasing observed booster seat use among child passengers in motor vehicles.Prospective, nonrandomized, controlled community intervention trial.The campaign was initiated in 4 communities in the greater Seattle, Wash, area between January 2000 and March 2001. Eight communities in Portland, Ore, and Spokane, Wash, served as control sites. We observed 3609 booster-eligible children (those aged 4-8 years and weighing 18-36 kg [40-80 lb]).Observed booster seat use 15 months after the start of the campaign.Before the campaign began, 13.3% of eligible children in the intervention communities and 17.3% in the control communities were using booster seats, adjusting for child age, driver seat belt use, and sex of driver. Fifteen months after the start of the campaign, adjusted booster seat use had increased to 26.1% in the intervention communities and 20.2% in the control communities (P =.008 for the difference in time trends between intervention and control communities).These data suggest that a multifaceted community education campaign can significantly increase the use of child booster seats.
Abstract 3163: Exploration of microRNA-34a effects in human glioma cell lines
Authors: Alexander Kofman, Fadila Guessous, Charles G. diPierro, Evan Dupart, Yongde Bao, Susan Dhamala, Christopher Letson, Christopher Letson, So Yeon Park, Lukasz Marcinkiewicz, Roger Abounader
Journal: Cancer Research (2012)

Abstract We have previously demonstrated that miR34a targets and downregulates multiple oncogenes, and therefore it may be considered as a potent tumor suppressor factor. In this report we show that miR34a expression is strictly dependent on the ability of major tumor suppressor protein TP53 to bind to miR34a transcriptional regulatory elements. In order to further investigate the effects of miR34a we generated a panel of human glioma cell lines where both miR34a and copGFP gene reporter are expressed in a tet-inducible manner. The constitutive expression of cyan fluorescent protein, the mutant GFP derived from Aequorea Victoria, and tet-inducible expression of copGFP derived from Anthozoa allows co-localizing and tracking both tet-induced and non-induced cells in vivo. We present data indicating that miR34a-caused inhibition of cell proliferation both in vitro and in vivo is due to the down-regulation of cyclin D1 and transcriptional factors E2F3 and E2F5. We show that miR199a, which targets other cyclins and cyclin-dependent kinases and therefore complements the action of miR34a, is up-regulated upon miR34a overexpression. miR199a-5P and miR199a-3P, but not miR34a, target E2F6 and USP7 correspondingly. Overexpression of miR34a using tet-inducible cell lines and lentiviral vectors downregulated E2F6 and USP7 on the 5th day after induction/transduction. However, at 48-72 hours after p53 overexpression accompanied by the modest upregulation of miR34a no changes in miR199a levels were observed. The results indicate that miR34a induces miR199a overexpression indirectly, most probably at the transcriptional level, thus eliciting the synergistic anti-tumor effects. We have also found that overexpression of miR34a in tet-inducible manner significantly inhibits the growth of brain tumors and prolongs the survival of immunodeficient animals. Finally, we show that miR34a targets and downregulates phosphoprotein enriched in astrocytes-15, which has been reported to promote autophagy and contribute to the resistance to radiation therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3163. doi:1538-7445.AM2012-3163
A CASE OF EXTRA-OCULAR MUSCULAR PARESIS TREATED WITH GLYCINE
Authors: H. H. Beard
Journal: JAMA (1934)

To the Editor:—  A man, aged 32, first came to one of us (H. N. B.), Aug. 27, 1928, complaining of a recent diplopia. Paresis was present of all the muscles of the left eye supplied by the internal and external branches of the third cranial nerve. There was only a slight ptosis of the upper lid. The patient has been under systemic treatment ever since that time. He had an extremely sluggish patella reflex. Blood examination was negative. The Wassermann reaction of the blood and spinal fluid was negative. He was given several doses of neoarsphenamine and a mercury compound and potassium iodide internally. Examination of the paranasal sinuses gave negative results. He had some infected teeth, which were removed. The possibility of multiple sclerosis was considered and a diagnosis was made by an English neurologist of myasthenia gravis, though there was a distinct inequality of the pupils.  The