tbuckley/cabot-search huggingface dataset:
Abstract 5518: Characterization of invariant natural killer T cells in patients with advanced melanoma treated with CTLA4 blockade and dendritic cell vaccination
Authors: Javier -. Ibarrondo, Begoña -. Comin-Anduix, Yohan -. Lee, Thinle -. Chodon, Hooman -. Sazegar, Jason -. Jalil, Bartosz -. Chmielowski, Richard C. Koya, Jesus -. Gomez-Navarro, Beth D. Jamieson, Antoni -. Ribas
Journal: Cancer Research (2011)

Abstract Background. Invariant CD1d-restricted T cells (iNKT) are a T lymphocyte subset with a key role in the innate and adaptive immune systems and have been implicated in protection against cancer. iNKT cells are activated by lipid antigen presentation by CD1d on myeloid dendritic cells (mDC). Upon activation, iNKT produce Th1 and Th2 cytokines. CD4+ iNKT cells have a Th2 profile, while CD4- and CD4-CD8- (DN) subsets, behave as Th1 T-cells. We studied the phenotype of iNKT in patients treated with the anti-CTLA4 monoclonal antibody tremelimumab alone or combined with MART-126-35 peptide-pulsed dendritic cells (MART-1/DC) to explore possible associations between iNKT with treatment outcomes. Methods: Peripheral blood mononuclear cells (PBMC) were obtained before and after treatment with tremelimumab alone (n=21) or tremelimumab with MART-1/DC (n=8). There were 4 patients with an objective response in the combined therapy group and 3 patients with an objective response in the tremelimumab alone group. The number and phenotype of T cell and iNKT were characterized by multi-color flow cytometry. Results. Approximately one month after the first dose of combined treatment the percentage of iNKT-cells increased over baseline, while the percentage of iNKT cells decreased in patients treated with tremelimumab alone. In patients receiving combined treatment, those with a clinical response had a significantly higher iNKT number than non-responders. Overall, iNKT phenotypes did not change in either treatment group during treatment. However, clinical responders receiving combined therapy exhibited a high percentage of iNKT-CD8+ cells and low percentages of iNKT-CD4+. In contrast, in the non-responders and patients treated with tremelimumab alone, the iNKT CD8 to CD4 subset ratio was inverted. The combined iNKT subsets (CD4+, DN+, and CD8+) shared a common phenotype of CCR5+, CD62L+ and CD45RA+ and the phenotype did not change over time. For the tremelimuamb cohort, a CCR7-CD45RA- phenotype appeared and increased within the iNKT-CD4+ and CD8+ subsets after dosing. Conclusions. Treatment with the anti-CTLA4 antibody tremelimumab induced changes in the percentage of iNKT cells which were more pronounced when co-administered with dendritic cell vaccines. iNKT cells may be a new cell subset mediating in the mechanism of action of CTLA4 blocking antibodies. 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 5518. doi:10.1158/1538-7445.AM2011-5518
Hydrophobic Surfactant Proteins in Lung Function and Disease
Authors: Jeffrey A. Whitsett, Timothy E. Weaver
Journal: New England Journal of Medicine (2002)

Pulmonary surfactants consist of phospholipids and the hydrophobic proteins surfactant protein B and surfactant protein C. These surfactants keep the alveoli in the lung open to the atmosphere. Mutations in the genes encoding these proteins cause a variety of pulmonary syndromes. The pulmonary diseases associated with some of these mutations exemplify the consequences of the accumulation of misfolded proteins in tissue.
Inflammatory Fibroid Polyp of the Stomach
Authors: M. Stolte, G. Finkenzeller
Journal: Endoscopy (1990)

Among 3,200 polyps of the stomach, we diagnosed inflammatory fibroid polyp in 143 patients (4.5 %). The average age of the patients was 63.6 years (women) and 63.9 years (men), the sex ratio being 1.6 women to 1.0 men. In 77.6 % of the cases, the polyp was located within the antrum, in 9.8 % in the angular notch region. 1.4 % in the pylorus, and 0.7 % each in the fundus and cardia. The characteristic histological feature of these lesions is an eosinophil-containing, loosely structured fibrous tissue comprising an onion-skin-like arrangement of reticular fibers with spindle-shaped nuclei localized in the submucosa and the base of the mucosa. The polypous bulging mucosa was eroded in 26.8 % and ulcerated in 3.5 % of the cases. A comparison of the 147 cases collected from the literature with our own 143 cases revealed no differences. The rarity of inflammatory fibroid polyps in the stomach, their predominant location in the antrum, the age distribution and the observation that, after removal, these lesions do not recur, all go to suggest that the lesion is a reactive process (allergic or foreign body reaction), possibly a residual state following infestation by a parasite larva.
Health and wellbeing boards need to step up to meet local health needs, says report
Authors: J. Wise
Journal: BMJ (2013)

The health policy think tank the King’s Fund has said that England’s new health and wellbeing boards have made a good start in establishing themselves but need to change up a gear if they are to avoid being sidelined.

The fund carried out a survey of the 152 health and wellbeing boards in England, of which 70 replied (response rate 46%). The boards were set up on 1 April 2012 and operated on a shadow basis for their first year. This second …
Abstract 570: Breast cancer chemopreventive activity of a novel amide derivative of sulindac involves inhibition of PDE5, activation of PKG, and attenuation of Wnt/β-catenin signaling
Authors: Heather N. Tinsley, Bernard D. Gary, Jason Whitt, Wei Zhang, Xi Chen, Adam B. Keeton, Clinton J. Grubbs, William E. Grizzle, Gary A. Piazza
Journal: Cancer Research (2012)

Abstract The nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX2) inhibitors demonstrate promising chemopreventive activity against a number of cancer types, including breast cancer. Unfortunately, potentially fatal toxicities associated with COX inhibition have precluded the development of these drugs for such indications. However, some studies suggest that their anticancer activity may be due to COX-independent mechanisms, suggesting the ability to target such mechanisms for the development of potentially safer and more effective chemopreventive agents. Here we describe a novel amide derivative of the NSAID sulindac sulfide (SS), termed sulindac sulfide amide (SSA). SSA lacked the ability to inhibit either COX1 or COX2 but demonstrated as much as a twenty-fold increase in potency to inhibit growth and induce apoptosis of breast tumor cells compared to SS. Moreover, SSA was selective for tumor cells, having no measurable effect on apoptosis of nontumorigenic mammary epithelial cells. As we have shown previously with SS, SSA inhibited the cGMP specific phosphodiesterase 5 (PDE5) enzyme. This resulted in accumulation of intracellular cGMP and activation of cGMP-dependent protein kinase (PKG) at concentrations comparable to those that induced breast tumor cell apoptosis. Mirroring the effects on PKG, SSA also resulted in decreased Wnt/β-catenin signaling, including decreased expression of the Tcf/Lef controlled proteins, cyclin D1 and survivin. Furthermore, SSA caused a 50% reduction in the incidence and a 30% reduction in the multiplicity of mammary tumors using the MNU model of mammary carcinogenesis. Interestingly, mammary tumors induced by MNU displayed high levels of PDE5 expression. These findings further demonstrate the COX-independent nature of the anticancer activity of certain NSAIDs, provide additional evidence that PDE5 may serve as an effective target for breast cancer chemoprevention, and reveal the utility of chemically modifying the NSAIDs to remove COX inhibitory activity while enhancing anticancer activity in order to produce safer and more effective chemopreventive agents. 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 570. doi:1538-7445.AM2012-570
Three Feet Tall and Thirty Pounds
Authors: Michael R. Clemmens
Journal: JAMA (1986)

We met late one night in the pediatric intensive care unit. He was the patient; I was the intern. Earlier that day he had been exploring his world with a vigor that only a 3-year-old could know. He had found a parked motorcycle, tried to climb aboard, and succeeded only in pulling it over, pinning himself beneath it. He was found moments later, nearly lifeless. The wonders of basic and advanced life support restored his heartbeat, but he was still in a deep coma when he arrived in the ICU that night. At first glance he seemed the prototypic 3-year-old: three feet tall and thirty pounds. He was just beginning to lose his toddler's potbelly. Blond and fair skinned, he had blue eyes that hours before must surely have twinkled with warmth and excitement. But now they were glazed, his stare empty and searching. His brain had begun to swell,
`Global Package' Saves Money but Stirs Criticism
Authors: Charles Marwick
Journal: JAMA (1993)

BY PACKAGING surgeons' and physicians' fees into a single negotiated charge, four hospitals have saved Medicare $13.6 million in the course of performing 2552 coronary bypass procedures during the last 2 years. This is the essence of the first results from the still unfinished Medicare-Participating Heart Bypass Demonstration Project.  If we apply the overall average discount to the project, which is 13%, to the 147 000 Medicare patients operated on in 1992, we are looking at a $533-million savings or just over half a billion dollars for this procedure alone, says Richard L. Prager, MD, medical director of the demonstration project at St Joseph Mercy Hospital, Ann Arbor, Mich. Prager spoke at a press conference in Washington, DC, at which interim results from the project were announced.  Mercy is one of the four original participating hospitals, along with Boston (Mass) University Medical Center Hospital; Ohio State University Hospitals, Columbus; and
Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: histologic, biochemical, and cell proliferation endpoints.
Authors: R R Maronpot, J F Foley, K Takahashi, T Goldsworthy, G Clark, A Tritscher, C Portier, G Lucier
Journal: Environmental Health Perspectives (1993)

The present study examines the dose-response relationship for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) promotion of histologic and biochemical parameters by using a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats initiated with a single intraperitoneal dose of 175 mg of diethylnitrosamine (DEN)/kg body weight at 70 days of age. Starting 2 weeks after initiation, treatment groups of 8-10 rats were given TCDD by gavage in corn oil once every 2 weeks for 30 weeks. Doses were 3.5, 10.7, 35.7, and 125 ng TCDD/kg body weight/day. A significant body weight reduction was present in the noninitiated group that received 125 ng TCDD. Relative liver weight was statistically increased in initiated rats treated with > or = 10.7 ng TCDD and in noninitiated rats treated with > or = 35.7 ng TCDD. Histopathologic evidence of cytotoxicity was dose-related in all TCDD-treated groups. There was a statistically significant dose response in the bromodeoxyuridine (BrdU) S-phase labeling index (LI) in the DEN-initiated rats (p < 0.01) and a marginally significant trend in the saline-treated rats (p = 0.10), but proliferating cell nuclear antigen S-phase LI and growth fraction within altered hepatic foci showed no increase. Among the DEN-initiated groups there was a significant increase in glutathione S-transferase altered hepatic foci stereological parameters in the 125 ng TCDD group. This study demonstrates that dose-response relationships for TCDD's effects on cell proliferation growth of altered hepatic foci are different from previously reported effects on P450 gene expression, indicating that different biological or biochemical responses may exhibit different dose-response relationships.(ABSTRACT TRUNCATED AT 250 WORDS)
Asymptomatic Bacteriuria and Leukocyturia in Type 1 Diabetic Children and Young Adults
Authors: Barnabás Rózsai, Éva Lányi, Gyula Soltész
Journal: Diabetes Care (2003)

In the study of Geerlings et al. (1), one of five type 1 diabetic women had asymptomatic bacteriuria (ASB). In the few studies of diabetic children a low prevalence of ∼1% was found (2–4). Our clinical experience suggested a much higher prevalence; therefore, we decided to estimate the prevalence and possible risk factors of ASB in type 1 diabetic children.

There were 178 (86 male) type 1 diabetic children and young adults (age 15.1 ± 5.9 years) with diabetes duration of 6.2 (3.0–10.1) [median (interquartile range)] years who participated in this study.

The control group consisted of 194 (103 male) school children/medical students (14.4 ± 5.1 years). After careful cleaning, midstream voiding morning urine samples were collected and immediately cultured on 2 consecutive days.

ASB was defined as the presence of ≥105 colony-forming units/ml of one and …
Recurrent respiratory tract infections during the first 3 years of life and atopy at school age
Authors: W. Nystad, A. Skrondal, F. Njå, Ø Hetlevik, K.‐H. Carlsen, P. Magnus
Journal: Allergy (1998)

The hypothesis that infections reduce the risk of atopy was investigated by estimating the association between recurrent respiratory tract infections during the first 3 years of life and atopy at school age.According to surveys in three different areas of Norway, children were classified into three groups: asthma, wheeze without asthma (wheeze), and no asthma/no wheeze. The skin prick test (SPT) was conducted on a stratified random sample of children (n = 502). The outcome was at least one positive SPT. The exposure variable was retrospective parental report of respiratory tract infections during the first 3 years of life.Infections were negatively associated with atopy, crude odds ratio (cOR) = 0.3, 95% confidence interval (95% CI) 0.1-0.7, in the asthma group. A similar association was present in children with wheeze cOR = 0.4 (95% CI 0.1-1.2). The number of siblings was not associated with atopy in any group. Infections remained negatively associated with atopy in children with asthma, aOR = 0.3 (95% CI 0.1-0.7), in a logistic regression model adjusting for confounding factors. A similar pattern was present in the wheeze group.Recurrent respiratory tract infections during the first 3 years of life are negatively associated with atopy at school age in children with asthma.
Penicillin for Hand Infections
Authors: G. J. Grossmark, L. W. Plewes
Journal: BMJ (1945)

Penicillin is effective against all the common causal organisms of ophthalmia neonatorum, including the presumed virus of inclusion blennorrhoea.Local penicillin therapy is likely to replace general sulphonamide treatment as the method of choice in ophthalmia neonatorum.Thanks are due to Dr. E.
Scleromyxedema associated with scleroderma renal disease and acute psychosis
Authors: Gary R. Kantor, Wilma F. Bergfeld, William E. Katzin, Owen D. Reynolds, Augustine P. Biscardi, David M. Lobur, Tim A. Box, Martin J. Schreiber, Norman B. Ratliff
Journal: Journal of the American Academy of Dermatology (1986)
Bronchioloalveolar Carcinoma (Lepidic Growth) Component Is a More Useful Prognostic Factor than Lymph Node Metastasis
Authors: Yoichi Anami, Tatsuo Iijima, Kenji Suzuki, Jun Yokota, Yuko Minami, Hiromi Kobayashi, Kaishi Satomi, Yoshimasa Nakazato, Masafumi Okada, Masayuki Noguchi
Journal: Journal of Thoracic Oncology (2009)
Low Incidence of Type 1 Diabetes in Iran
Authors: Gholam Reza Pishdad
Journal: Diabetes Care (2005)

There is a worldwide increase in the incidence of type 1 diabetes (1–3). This increase, in conjunction with the lack of complete concordance in monozygotic twin pairs, points to the importance of environmental factors (3). Useful clues about these environmental factors may be obtained by studying geographical variation in incidence in relation to the characteristics of different countries. There is a paucity of information regarding type 1 diabetes in Iran. It was the purpose of this study to provide some baseline data regarding this disease in Iran.

The surveyed area was the southern province of Fars in the 5-year time period between 21 March 1991 and 20 March 1996. The region, which had a population of 3,800,000 in 1996, covers an area of 133,000 km2 and is the largest province in southern Iran. Of the whole Iranian population, 10% live in southern Iran and 64% are residents of Fars.

### Primary ascertainment procedure

In a prospective study from 21 March 1991 to 20 March 1996, all type 1 diabetic patients with age at onset of disease <30 years were selected from diabetic patients of endocrine and diabetes clinics and university hospitals of southern Iran. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus criteria (4) were used in the assessment of the diagnosis …
RAS blockade decreases blood pressure and proteinuria in transgenic mice overexpressing rat angiotensinogen gene in the kidney
Authors: S. Sachetelli, Q. Liu, S.-L. Zhang, F. Liu, T.-J. Hsieh, M.-L. Brezniceanu, D.-F. Guo, J.G. Filep, J.R. Ingelfinger, C.D. Sigmund, P. Hamet, J.S.D. Chan
Journal: Kidney International (2006)
Abstract 2767: Congenital Heart Disease And Hypertrophic Cardiomyopathy In Noonans Syndrome: Determinants Of Outcome.
Authors: Edward J Hickey, Maryam Elmi, Kentaro Asoh, rohit Mehta, William G Williams, signe Holm-Larsen, Brian W McCrindle, Cedric Manlhiot, Lee Benson
Journal: Circulation (2007)

To further understand the implications of hypertrophic cardiomyopathy (HCM) in Noonans syndrome (NS), we characterized our cardiovascular experience of NS over 40 years. All 141 children referred to our cardiovascular service since 1966 NS were reviewed. Time-related outcomes were modeled using multiphase parametric techniques and subjected to risk-hazard analysis with bootstrapping. Survival outcomes in NS HCM were then compared with a contemporaneous series of children with non-NS HCM (N=120) from our institution. The incidences of cardiac anomalies were: PV dysplasia, 56%; ASD, 24%; HCM, 23%; VSD, 11%; MV dysplasia, 6%; left SVC, 5%; tetralogy of Fallot and coarctation 3%. HCM in excess of what would be expected based on type and severity of cardiovascular anomaly was diagnosed in 30/141 (23%). In 18 of these (57%), HCM co-existed with an associated anomaly (PV dysplasia=14, VSD=2, ASD=4, MV dysplasia=4 and coarctation=1). In contrast, all 120 non-NS pediatric HCM at our institution had no associated cardiovascular anomaly. Cardiac surgery was necessary in 45 (32%) and was predicted by septal defects, RVOT gradient and LVOT gradient &gt;30mmHg. Surgery was directed to the RVOT or septum in &gt;75% cases. Left myectomy was necessary in only 5 (11%). Overall survival was 92% +/-3 at 10 years and death was independently predicted by HCM and LVOT obstruction. Risk-adjusted late-phase hazard for death was significantly higher for NS HCM than non-NS HCM (p=.008). Conclusions HCM in NS usually occurs in asociation with other lesions. HCM in NS carries a worse late prognosis than non-NS HCM. Survival outcomes are good, although the presence of HCM is an independent predictor of death.
A tough nut to crack
Authors: Kamran Abbasi
Journal: BMJ (2005)

<h3>Background</h3> Adverse childhood socioeconomic status (cSES) predicts higher late-life risk of memory loss and dementia. Veterans of U.S. wars are eligible for educational and economic benefits that may offset cSES disadvantage. We test whether cSES disparities in late-life memory and dementia are smaller among veterans than non-veterans. <h3>Methods</h3> Data came from US-born men in the 1995–2014 biennial surveys of the Health and Retirement Study (n=7916 born 1928–1956, contributing n=38 381 cognitive assessments). Childhood SES was represented by maternal education. Memory and dementia risk were assessed with brief neuropsychological assessments and proxy reports. Military service (veteran/non-veteran) was evaluated as a modifier of the effect of maternal education on memory and dementia risk. We employed linear or logistic regression models to test whether military service modified the effect of maternal education on memory or dementia risk, adjusted for age, race, birthplace and childhood health. <h3>Results</h3> Low maternal education was associated with worse memory than high maternal education (β = −0.07 SD, 95% CI −0.08 to –0.05), while veterans had better memory than non-veterans (β = 0.03 SD, 95% CI 0.02 to 0.04). In interaction analyses, maternal education disparities in memory were smaller among veterans than non-veterans (difference in disparities = 0.04 SD, 95% CI 0.01 to 0.08, p = 0.006). Patterns were similar for dementia risk. <h3>Conclusions</h3> Disparities in memory by maternal education were smaller among veterans than non-veterans, suggesting military service and benefits partially offset the deleterious effects of low maternal education on late-life cognitive outcomes.
Outcomes and pathological review of a cohort of children with melanoma
Authors: J.A. Leman, A. Evans, W. Mooi, R.M. MacKie
Journal: British Journal of Dermatology (2005)

Prepubertal malignant melanoma is rare, pathological criteria are difficult and follow-up data on patients are lacking in the literature.To review prepubertal cases of melanoma diagnosed in the West of Scotland 1979-2002.Twenty cases were identified in whom melanoma was diagnosed before the age of 15. Pathological review was possible for 13 of 20 cases, and current follow-up information is available for all 20. Three pathologists not responsible for the original diagnosis reviewed the slides independently, in every case without knowledge of the outcome.Of the 13 cases reviewed, there was concordance of diagnosis between the three pathologists in 12 cases. Eight of the 13 cases reviewed were considered to be unusual naevi rather than melanoma. One child has died of melanoma and all three pathologists agreed with the original pathological diagnosis. One patient has experienced nodal metastases but is alive and disease-free 12 years later. The remaining 18 cases have had no recurrence since primary surgery 2-21 years ago.There may be a tendency to overdiagnose prepubertal melanoma. Good communication between clinician and pathologist and the use of an expert pathology panel is recommended before making the diagnosis.