tbuckley/cabot-search huggingface dataset:
Photochemical Restoration of Visual Responses in Blind Mice
Authors: Aleksandra Polosukhina, Jeffrey Litt, Ivan Tochitsky, Joseph Nemargut, Yivgeny Sychev, Ivan De Kouchkovsky, Tracy Huang, Katharine Borges, Dirk Trauner, Russell N. Van Gelder, Richard H. Kramer
Journal: Neuron (2012)
Effect of 3 months’ nasal steroid therapy on nasal T cells and Langerhans cells in patients suffering from allergic rhinitis
Authors: A. F. Holm, W.J. Fokkens, T. Godthelp, P.G. Mulder, T. M. Vroom, E. Rijntjes
Journal: Allergy (1995)

The effect of nasal corticosteroid therapy on allergic rhinitis is uncertain. In a double‐blind, placebo‐controlled study over 3 months, we investigated the influence of a new corticosteroid spray, fluticasone propionate aqueous nasal spray (FPANS), on Langerhans cells (CD1a + cells), HLA‐DR + cells, and T cells in nasal mucosa. Efficacy was evaluated by nasal symptom score. This treatment significantly decreased the number of CDla + cells and HLA‐DR + cells in the nasal mucosa. Furthermore, a clear trend of decreasing numbers of T cells in nasal epithelium was found. No change in nasal symptom score was found after the treatment period. These findings suggest that fluticasone propionate aqueous nasal spray decreases the antigen presentation in nasal allergy.
Health effects of diesel exhaust emissions
Authors: A. Sydbom, A. Blomberg, S. Parnia, N. Stenfors, T. Sandström, S-E. Dahlén
Journal: European Respiratory Journal (2001)

Epidemiological studies have demonstrated an association between different levels of air pollution and various health outcomes including mortality, exacerbation of asthma, chronic bronchitis, respiratory tract infections, ischaemic heart disease and stroke. Of the motor vehicle generated air pollutants, diesel exhaust particles account for a highly significant percentage of the particles emitted in many towns and cities. This review is therefore focused on the health effects of diesel exhaust, and especially the particular matter components. Acute effects of diesel exhaust exposure include irritation of the nose and eyes, lung function changes, respiratory changes, headache, fatigue and nausea. Chronic exposures are associated with cough, sputum production and lung function decrements. In addition to symptoms, exposure studies in healthy humans have documented a number of profound inflammatory changes in the airways, notably, before changes in pulmonary function can be detected. It is likely that such effects may be even more detrimental in asthmatics and other subjects with compromised pulmonary function. There are also observations supporting the hypothesis that diesel exhaust is one important factor contributing to the allergy pandemic. For example, in many experimental systems, diesel exhaust particles can be shown to act as adjuvants to allergen and hence increase the sensitization response. Much of the research on adverse effects of diesel exhaust, both in vivo and in vitro , has however been conducted in animals. Questions remain concerning the relevance of exposure levels and whether findings in such models can be extrapolated into humans. It is therefore imperative to further assess acute and chronic effects of diesel exhaust in mechanistic studies with careful consideration of exposure levels. Whenever possible and ethically justified, studies should be carried out in humans.
Histology of Lung Cancer in Relation to Prognosis
Authors: K. P. Goldman
Journal: Thorax (1965)

A retrospective survey was undertaken of all patients who attended Sully Hospital during the period 1 January 1954 to 1 October 1960, and who were thought to have primary carcinoma of the lung.Cases in which the diagnosis, on review, seemed doubtful were excluded.The material was analysed by age, sex, tumour histology, method of treatment, and survival.The histological classification of tumours was per- formed by one pathologist (Dr.R. M. E. Seal) and was not specially reviewed for this study.Classifica- tion was according to the predominant cell type.Tumours consisting mainly of well-differentiated cells 298 on August 19,
Dynamic intraventricular obstruction during dobutamine stress echocardiography. A new observation.
Authors: P A Pellikka, J K Oh, K R Bailey, B A Nichols, K H Monahan, A J Tajik
Journal: Circulation (1992)

BACKGROUND The implications of hypotension occurring during dobutamine stress echocardiography have not been elucidated. We observed in some patients that hyperdynamic left ventricular function developed during dobutamine stress echocardiography and hypothesized that intracavitary obstruction was occurring and might account for hypotension in some patients. METHODS AND RESULTS Fifty-seven consecutive patients undergoing dobutamine stress echocardiography underwent pulsed-wave and continuous-wave Doppler examination of the left ventricular cavity at rest and at peak dobutamine infusion. The development of an intraventricular gradient with dobutamine stress was defined as a late-peaking left ventricular Doppler velocity profile that exceeded basal velocity by at least 1 m/sec. During dobutamine stress testing, left ventricular outflow velocity or intracavitary velocity increased in all patients. Obstruction occurred in 12 patients (21%, group 1). Group 2 was the remaining 45 patients. Peak velocities in group 1 ranged from 2.0 to 5.0 m/sec (mean, 3.5 m/sec), and the mean increase from velocity at rest was 2.3 m/sec. The mean change in systolic blood pressure was significantly lower in patients in group 1 (-15 versus 4 mm Hg, p = 0.02). When the 18 patients with an ischemic response to stress testing (evidenced by new or worsening wall motion abnormalities) were excluded from analysis, systolic blood pressure response was still significantly different for the two groups (-19 versus 2 mm Hg, p = 0.03). CONCLUSIONS Dynamic left ventricular obstruction is a new observation; it may develop frequently in patients undergoing dobutamine stress echocardiography. Obstruction rather than ischemia may explain a decrease in blood pressure during dobutamine stress echocardiography.
Targeting of Apoptotic Macrophages and Experimental Atheroma With Radiolabeled Annexin V
Authors: Frank D. Kolodgie, Artiom Petrov, Renu Virmani, Navneet Narula, Johan W. Verjans, Deena K. Weber, Dagmar Hartung, Neil Steinmetz, Jean Luc Vanderheyden, Mani A. Vannan, Herman K. Gold, Chris P.M. Reutelingsperger, Leo Hofstra, Jagat Narula
Journal: Circulation (2003)

Apoptosis is common in advanced human atheroma and contributes to plaque instability. Because annexin V has a high affinity for exposed phosphatidylserine on apoptotic cells, radiolabeled annexin V may be used for noninvasive detection of apoptosis in atherosclerotic lesions.Atherosclerotic plaques were produced in 5 rabbits by deendothelialization of the infradiaphragmatic aorta followed by 12 weeks of cholesterol diet; 5 controls were studied without manipulation. Animals were injected with human recombinant annexin V labeled with technetium-99m before imaging. Aortas were explanted for ex vivo imaging, macroautoradiography, and histological characterization of plaque. Radiolabeled annexin V cleared rapidly from the circulation (T1/2, alpha 9 and beta 46 minutes). There was intense uptake of radiolabel within lesions by 2 hours; no uptake was seen in controls. The results were confirmed in the ex vivo imaging of the explanted aorta. Quantitative annexin uptake was 9.3-fold higher in lesion versus nonlesion areas; the lesion-to-blood ratio was 3.0+/-0.37. Annexin uptake paralleled lesion severity and macrophage burden; no correlation was observed with smooth muscle cells. DNA fragmentation staining of apoptotic nuclei was increased in advanced lesions with evolving necrotic cores, predominantly in macrophages; the uptake of radiolabel correlated with the apoptotic index.Because annexin V clears rapidly from blood and targets apoptotic macrophage population, it should constitute an attractive imaging agent for the noninvasive detection of unstable atherosclerotic plaques.
Long-Term Metabolic and Immunological Follow-Up of Nonimmunosuppressed Patients With Type 1 Diabetes Treated With Microencapsulated Islet Allografts
Authors: Giuseppe Basta, Pia Montanucci, Giovanni Luca, Carlo Boselli, Giuseppe Noya, Barbara Barbaro, Meirigeng Qi, Katie P. Kinzer, José Oberholzer, Riccardo Calafiore
Journal: Diabetes Care (2011)

To assess long-term metabolic and immunological follow-up of microencapsulated human islet allografts in nonimmunosuppressed patients with type 1 diabetes (T1DM).Four nonimmunosuppressed patients, with long-standing T1DM, received intraperitoneal transplant (TX) of microencapsulated human islets. Anti-major histocompatibility complex (MHC) class I-II, GAD65, and islet cell antibodies were measured before and long term after TX.All patients turned positive for serum C-peptide response, both in basal and after stimulation, throughout 3 years of posttransplant follow-up. Daily mean blood glucose, as well as HbA(1c) levels, significantly improved after TX, with daily exogenous insulin consumption declining in all cases and being discontinued, just transiently, only in patient 4. Anti-MHC class I-II and GAD65 antibodies all tested negative at 3 years after TX.The grafts did not elicit any immune response, even in the cases where more than one preparation was transplanted, as a unique finding, compatible with encapsulation-driven "bioinvisibility" of the grafted islets. This result had never been achieved with the recipient's general immunosuppression.
Determining True <i>HER2</i> Gene Status in Breast Cancers With Polysomy by Using Alternative Chromosome 17 Reference Genes: Implications for Anti-<i>HER2</i> Targeted Therapy
Authors: Chun Hing Tse, Harry C. Hwang, Lynn C. Goldstein, Patricia L. Kandalaft, Jesse C. Wiley, Steven J. Kussick, Allen M. Gown
Journal: Journal of Clinical Oncology (2011)

Purpose The ratio of human epidermal growth factor receptor 2 (HER2) to CEP17 by fluorescent in situ hybridization (FISH) with the centromeric probe CEP17 is used to determine HER2 gene status in breast cancer. Increases in CEP17 copy number have been interpreted as representing polysomy 17. However, pangenomic studies have demonstrated that polysomy 17 is rare. This study tests the hypothesis that the use of alternative chromosome 17 reference genes might more accurately assess true HER2 gene status. Patients and Methods In all, 171 patients with breast cancer who had HER2 FISH that had increased mean CEP17 copy numbers (&gt; 2.6) were selected for additional chromosome 17 studies that used probes for Smith-Magenis syndrome (SMS), retinoic acid receptor alpha (RARA), and tumor protein p53 (TP53) genes. A eusomic copy number exhibited in one or more of these loci was used to calculate a revised HER2-to-chromosome-17 ratio by using the eusomic gene locus as the reference. Results Of 132 cases classified as nonamplified on the basis of their HER2:CEP17 ratios, 58 (43.9%) were scored as amplified by using alternative chromosome 17 reference gene probes, and 13 (92.9%) of 14 cases scored as equivocal were reclassified as amplified. Among the cases with mean HER2 copy number of 4 to 6, 41 (47.7%) of 86 had their HER2 gene status upgraded from nonamplified to amplified, and four (4.7%) of 86 were upgraded from equivocal to amplified. Conclusion Our results support the findings of recent pangenomic studies that true polysomy 17 is uncommon. Additional FISH studies that use probes to the SMS, RARA, and TP53 genes are an effective way to determine the true HER2 amplification status in patients with polysomy 17 and they have important potential implications for guiding HER2-targeted therapy in breast cancer.
Hepatitis B in the Middle East: aspects of epidemiology and liver disease after infection.
Authors: A U Toukan
Journal: Gut (1996)

Postnatal horizontal transmission of hepatitis B virus (HBV) in early childhood seems to be the predominant method by which high hepatitis B carrier rates in the Middle East are maintained. The prevalence of hepatitis B surface antigen (HBsAg) positive status among siblings of HBV carriers is similar during childhood and adulthood, suggesting that childhood intrafamilial transmission patterns persist into adult life. There is a tendency for asymptomatic HBV carriers to have higher alanine aminotransferase (ALT) values, a feature that also tends to cluster in families. Infection in the first five years of life contributes most to the case load of chronic liver disease and thus to mortality from HBV. Mass hepatitis B immunisation programmes have been started, and while they may eventually reduce the HBV carrier state and liver disease loads significantly, prospects for total eradication of HBV in the near future are not good.
Dietary fats, health, and inequalities
Authors: J Lennert Veerman
Journal: BMJ (2015)

There’s nothing good about trans fats; a total ban would be best for public health

The stakes are high in matters of food and health. Everyone is exposed, so everyone is personally affected. Small increases in risk translate to large health impacts at the population level. Research is fraught with challenges, and powerful vested interests try to influence policy decisions, science, scientists, and practitioners.1

Two linked papers focusing on dietary fats add to these debates. De Souza and colleagues (doi:10.1136/bmj.h3978) reviewed the evidence on saturated fats and trans fats.2 The verdict on the health impact of saturated fats is still open, but industrial trans fats are clearly bad for health. Allen and colleagues (doi:10.1136/bmj.h4583) translate the evidence against trans fats into tangible effects on population health and health inequalities in England.3 Here, the debate centres on the best way to phase out industrial trans fats and how much state intervention is justified.

De Souza and colleagues performed a systematic review and meta-analysis of cohort studies that examined the association between saturated fats and trans fats and a range of cardiovascular outcomes and diabetes.2 They concluded that saturated fats were not associated …
PARENTERAL PLASMA PROTEIN MAINTAINS NITROGEN EQUILIBRIUM OVER LONG PERIODS
Authors: Roger Terry, William E. Sandrock, Robert E. Nye, G. H. Whipple
Journal: The Journal of Experimental Medicine (1948)

Proteinuria in normal dogs can be produced at will by parenteral injections of dog plasma. As the plasma injections are continued the plasma protein concentration rises and at some point protein begins to appear in the urine. The level of plasma protein concentration at which proteinuria appears in normal dogs ranges from 9.6 to 10.4 gm. per cent. This may be termed the renal threshold for proteinuria. Repeat experiments in the same dog show threshold levels to be practically identical. An interval of days (4 to 26 days) has been noted between the start of plasma protein injections and the appearance of the proteinuria. Larger doses of plasma shorten this interval and the critical plasma protein level is attained sooner. Considerable amounts of protein may appear in the urine-298 gm. protein during a 52 day period in one instance studied-yet the urine clears in 1 to 4 days after cessation of protein injections. Autopsy shows undamaged kidneys. Maximal levels of plasma protein concentration range from 10.0 to 11.5 gm. per cent. The highest levels are usually associated with maximal output of protein in the urine. It seems clear that plasma proteins readily pass cell barriers (or membranes) within the body, including the endothelium and epithelium of the renal glomerulus.
Risk Factors for Incident Stroke among Patients with End-Stage Renal Disease
Authors: Stephen L. Seliger, Daniel L. Gillen, David Tirschwell, Haimanot Wasse, Bryan R. Kestenbaum, Catherine O. Stehman-Breen
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Although patients with ESRD experience markedly higher rates of stroke, no studies in the US have identified risk factors associated with stroke in this population. It was hypothesized that black race, malnutrition, and elevated BP would be associated with the risk of stroke among patients with ESRD. Data from the United States Renal Data Systems were used. Adult Medicare-insured hemodialysis and peritoneal dialysis patients without a history of stroke or transient ischemic attack (TIA) were considered for analysis. The primary outcome was hospitalized or fatal stroke. Cox proportional hazards models were used to determine the associations between the primary predictor variables and stroke. The rate of incident stroke was 33/1,000 person-years in the study sample. After adjustment for age and other patient characteristics, three markers of malnutrition were associated with the risk of stroke—serum albumin (per 1 g/dl decrease, hazard ratio [HR] = 1.43), height-adjusted body weight (per 25% decrease, HR = 1.09), and a subjective assessment of undernourishment (HR = 1.27)—as was higher mean BP (per 10 mmHg, HR = 1.11). The association between black race varied by cardiac disease status, with blacks estimated to be at lower risk than whites among individuals with cardiac disease (HR = 0.74), but at higher risk among individuals without cardiac disease (HR = 1.24). This study confirms the extraordinarily high rates of stroke in ESRD patients on dialysis and identifies high mean BP and malnutrition as potentially modifiable risk factors. The association between black race and stroke differs by cardiac disease status; the reasons for this differing effect of race deserve further investigation. E-mail: [email protected]
Private commissioning plan raises question over conflicts of interest
Authors: Adrian O'Dowd
Journal: BMJ (2005)

A strategic health authority has postponed its plans to make one of its primary care trusts subcontract its commissioning function to an outside body, possibly in the private sector.

Following widespread protest, it has now said that the change will not occur until next summer.

The proposal, made by Thames Valley Strategic Health Authority last month, was part of the authority's submission to the Department of Health on how it plans to reconfigure primary care—something that all health authorities have had to do.

What is different about Thames Valley's case is its suggestion that it would create a new, larger version of Oxfordshire Primary Care Trust and tender for the management …
Functional Cooperation of RKTG with p53 in Tumorigenesis and Epithelial–Mesenchymal Transition
Authors: Yuhui Jiang, Xiaoduo Xie, Zhigang Li, Zheng Wang, Yixuan Zhang, Zhiqiang Ling, Yi Pan, Zhenzhen Wang, Yan Chen
Journal: Cancer Research (2011)

Raf kinase trapping to Golgi (RKTG) is a potential tumor suppressor gene due to its negative roles in regulating Ras/Raf/MEK/ERK (extracellular signal-regulated kinase) pathway and GPCR (G protein-coupled receptor) Gβγ subunit signaling. Interestingly, RKTG-deficient mice are free of tumors, although they are prone to form skin cancer on carcinogen administration. On the other hand, p53 is a well-characterized tumor suppressor gene and p53 heterozygous mice develop sarcoma and other tumors starting from 12 months of age. In RKTG-null mouse embryonic fibroblasts, lypophosphatidic acid (LPA), but not EGF (epidermal growth factor), could stimulate hyperphosphorylation of AKT and GSK3β, accompanied by increases in phosphorylation of p53 at Ser15 and accumulation of p53, as well as its target genes p21 and p16. Spontaneous skin cancer-like tumors were detected in about 25% of RKTG nullizygous and p53 heterozygous mice within 7 months of age. Hyperplasia and epithelial-mesenchymal transition (EMT) were observed in the tumor-overlying epidermis, in which LOH of p53 occurred and EMT features emerged. In p53-mutated A431 epithelial carcinoma cells, knockdown of RKTG led to enhancement of LPA-stimulated AKT and GSK3β phosphorylation, together with increased accumulation of β-catenin and appearance of EMT features that were antagonized by p53 overexpression. In HepG2 epithelial cells, LPA-stimulated AKT phosphorylation and EMT features reached maximum when both RKTG and p53 were simultaneously silenced. In summary, these results not only indicate that RKTG has an in vivo tumor suppressor function to cooperate with p53 in tumorigenesis but also suggest that p53 has an EMT checkpoint function and the loss of this function can combine with loss of RKTG to drive EMT and tumor progression.
Phospholemman-Phosphorylation Mediates the β-Adrenergic Effects on Na/K Pump Function in Cardiac Myocytes
Authors: Sanda Despa, Julie Bossuyt, Fei Han, Kenneth S. Ginsburg, Li-Guo Jia, Howard Kutchai, Amy L. Tucker, Donald M. Bers
Journal: Circulation Research (2005)

Cardiac sympathetic stimulation activates beta-adrenergic (beta-AR) receptors and protein kinase A (PKA) phosphorylation of proteins involved in myocyte Ca regulation. The Na/K-ATPase (NKA) is essential in regulating intracellular [Na] ([Na]i), which in turn affects [Ca]i via Na/Ca exchange. However, how PKA modifies NKA function is unknown. Phospholemman (PLM), a member of the FXYD family of proteins that interact with NKA in various tissues, is a major PKA substrate in heart. Here we tested the hypothesis that PLM phosphorylation is responsible for the PKA effects on cardiac NKA function using wild-type (WT) and PLM knockout (PLM-KO) mice. We measured NKA-mediated [Na]i decline and current (IPump) to assess beta-AR effects on NKA function in isolated myocytes. In WT myocytes, 1 micromol/L isoproterenol (ISO) increased PLM phosphorylation and stimulated NKA activity mainly by increasing its affinity for internal Na (Km decreased from 18.8+/-1.4 to 13.6+/-1.5 mmol/L), with no significant effect on the maximum pump rate. This led to a significant decrease in resting [Na]i (from 12.5+/-1.8 to 10.5+/-1.4 mmol/L). In PLM-KO mice under control conditions Km (14.2+/-1.5 mmol/L) was lower than in WT, but comparable to that for WT in the presence of ISO. Furthermore, ISO had no significant effect on NKA function in PLM-KO mice. ATPase activity in sarcolemmal vesicles also showed a lower Km(Na) in PLM-KO versus WT (12.9+/-0.9 versus 16.2+/-1.5). Thus, PLM inhibits NKA activity by decreasing its [Na]i affinity, and this inhibitory effect is relieved by PKA activation. We conclude that PLM modulates the NKA function in a manner similar to the way phospholamban affects the related SR Ca-ATPase (inhibition of transport substrate affinity, that is relieved by phosphorylation).
Classification of Race and Ethnicity: Implications for Public Health
Authors: Vickie M. Mays, Ninez A. Ponce, Donna L. Washington, Susan D. Cochran
Journal: Annual Review of Public Health (2003)

Emerging methods in the measurement of race and ethnicity have important implications for the field of public health. Traditionally, information on race and/or ethnicity has been integral to our understanding of the health issues affecting the U.S. population. We review some of the complexities created by new classification approaches made possible by the inclusion of multiple-race assessment in the U.S. Census and large health surveys. We discuss the importance of these classification decisions in understanding racial/ethnic health and health care access disparities. The trend toward increasing racial and ethnic diversity in the United States will put further pressure on the public health industry to develop consistent and useful approaches to racial/ethnic classifications.