tbuckley/cabot-search huggingface dataset:
1077. Sequences from the Human Type 1α2 Procollagen Promoter Mediate Osteoblast- Specific Plasmid Nuclear Import
Authors: David A. Dean, Cindy Stivers, Tom A. Linkhart, Donna D. Strong
Journal: Molecular Therapy (2006)

Two major problems limiting the use of non-viral gene therapy include the low efficiency of gene transfer seen with non-viral vectors and limited methods for cell-specific targeting and expression. We and others have shown that translocation of plasmid DNA into the nucleus is an important rate-limiting step in gene transfer that affects transgene expression levels in non-dividing cells. Further, we have identified several DNA sequences that mediate the nuclear import of plasmids in non-dividing cells, thereby acting as DNA nuclear targeting sequences. These sequences contain multiple binding sites for transcription factors that allow for the formation of protein- DNA complexes in the cytoplasm that are actively transported into the nucleus of the non-dividing cell using nuclear localization signals present on the transcription factors, and hence the protein-DNA complex. We have previously identified both a universal sequence that acts in all cell types (the SV40 enhancer) and sequences that act in specific cell types based on the property that they bind cell- specific transcription factors (e.g., the SMGA promoter for use in smooth muscle cells). In order to identify a DNA nuclear targeting sequence that is restricted to osteoblast lineage cells, we tested a number of osteoblast-specific promoters for nuclear import activity, including those from osteocalcin, collagen, BSP and Runx2 genes. Although all of these promoters showed robust expression of reporter genes following transfection into dividing osteoblasts, when microinjected into the cytoplasm of human or rat osteoblast cell lines, only the human type Iα2 procollagen (hcolIα2) promoter had the ability to mediate nuclear import of the plasmid in the absence of cell division. This sequence did not support DNA nuclear import in chondrocytes, fibroblasts and marrow stromal cells, suggesting that it is osteoblast-specific. Site-directed mutagenesis of putative transcription factor binding sites indicated that multiple response elements were required for osteoblast specific nuclear targeting, including those for AP-1, AP-2, Nkx3, SRF, Krox20, and an E-box binding protein. Taken together, these results suggest that the hCol1α2 promoter contains a novel osteoblast-specific DNA nuclear targeting sequence that can be used to increase nonviral gene transfer and transgene expression uniquely in osteoblasts, thereby increasing the safety profile by specifically targeting osteoblasts in skeletal tissue for gene therapy. The research reported in this abstract was supported by the Dept of the Army Cooperative Agreement # (DAMD17-97-2-7016). The views and content of the information does not necessarily reflect the position or the policy of the government or NMTB, and that no official endorsement should be inferred.
Metabolic Activity Measured by F-18 FDG PET in Natural Killer-Cell Lymphoma Compared to Aggressive B- and T-Cell Lymphomas
Authors: Winnie K. S. Chan, Wing-Yan Au, Ching-Yee O. Wong, Raymond Liang, Anskar Y. H. Leung, Yok-Lam Kwong, Pek-Lan Khong
Journal: Clinical Nuclear Medicine (2010)

We aim to compare the metabolic activity by F-18 fluorodeoxyglucose (FDG) uptake across the various histologic subtypes of non-Hodgkin lymphoma (NHL) in a single center, with particular interest in the natural killer (NK)-cell lymphoma subtype for which literature is scarce because of the rarity of these lymphomas in Western populations.We retrospectively evaluated the FDG-avidity of pretreatment positron emission tomography-computed tomography scans of 117 consecutive NHL patients by measuring the lesion with the highest maximum standardized uptake value (SUV(max)) in each patient. Mean SUV(max) of 4 major groups of NHL; aggressive B-cell (n = 63), indolent B-cell (n = 31), NK-cell (n = 14) and aggressive T-cell lymphoma (n = 9), was compared using one-way analysis of variance. P value <0.05 was considered statistically significant.SUV(max) (mean +/- standard deviation) of NK-cell lymphoma (9.2 +/- 4.5) was significantly lower than aggressive B-cell lymphoma (14.1 +/- 6.4) (P = 0.013), similar to aggressive T-cell lymphoma (7.6 +/- 3.9) and significantly higher than that of indolent B-cell lymphoma (5.3 +/- 3.1) (P = 0.039).The metabolic phenotype, characterized by FDG uptake of the various NHL subtypes is described. Although NK-cell lymphomas demonstrate high metabolic activity, SUV(max) is significantly lower than its aggressive B-cell counterparts. This may reflect the large amount of coagulative necrosis and inflammatory component of the tumor, and the relatively slower tumor growth rate compared with aggressive B-cell lymphomas.
Influence of Postshock Epicardial Activation Patterns on Initiation of Ventricular Fibrillation by Upper Limit of Vulnerability Shocks
Authors: Nipon Chattipakorn, Jack M. Rogers, Raymond E. Ideker
Journal: Circulation (2000)

Background —Shocks of identical strength and timing sometimes induce ventricular fibrillation (VFI) and other times do not (NoVFI). To investigate this probabilistic behavior, a shock strength near the upper limit of vulnerability, ULV 50 , was delivered to yield equal numbers of VFI and NoVFI episodes. Methods and Results —In 6 pigs, a 504-electrode sock was pulled over the ventricles. ULV 50 was determined by scanning the T wave. S 1 pacing was from the right ventricular apex. Ten S 2 shocks of approximate ULV 50 strength were delivered at the same S 1 -S 2 coupling interval. Intercycle interval (ICI) and wave front conduction time (WCT) were determined for the first 5 postshock cycles. ICI and the WCT of cycle 1 were not different for VFI versus NoVFI episodes ( P =0.3). Beginning at cycle 2, ICI was shorter and WCT was longer for VFI than NoVFI episodes ( P &lt;0.05). Conclusions —The first cycle after shocks of the same strength (ULV 50 ) delivered at the same time has the same activation pattern regardless of shock outcome. During successive cycles, however, a progressive decrease in ICI and increase in WCT occur during VFI but not NoVFI episodes. These findings suggest shock outcome is (1) deterministic but exquisitely sensitive to differences in electrophysiological state at the time of the shock that are too small to detect or (2) probabilistic and not determined until after the first postshock cycle.
Alzheimer's-Linked Protein Found to Be Skin Deep, but Potential New Therapies See Beauty of It
Authors: Teri Randall
Journal: JAMA (1991)

THE BRAIN no longer corners the amyloid β-protein market. Sensitive assays have recently detected the notorious protein in several nonneural tissues of patients with Alzheimer's disease, including the skin, intestine, and adrenal gland. Researchers say the discovery has major implications for the pathogenesis and treatment of this disease. The finding has come as a surprise to investigators, even to the researchers at Harvard Medical School, Boston, Mass, who conducted the experiments. "It has always been assumed, since Alzheimer described the disease in 1906, that it involved only the brain," says Dennis Selkoe, MD, codirector of Brigham and Women's Hospital's Center for Neurologic Diseases and professor of neurology and neuroscience at Harvard. The subclinical deposition of small amounts of amyloid β-protein in nonneural tissues lends support to the hypothesis, yet to be proven, that this protein originates in the bloodstream, or is produced locally in a variety of organs. <h3>New Assay</h3>
Acute Presentation of Fetal Hypertrophic Cardiomyopathy in a Type 1 Diabetic Pregnancy
Authors: Federico Prefumo, Claudio Celentano, Francesca Presti, Pierangela De Biasio, Pier Luigi Venturini
Journal: Diabetes Care (2005)

The incidence of intrauterine fetal death in type 1 diabetic patients is significantly higher than in the general population (1). Although vascular disease, poor glycemic control, polyhydramnios, fetal macrosomia, and preeclampsia are associated with a higher incidence of fetal death, the etiology of the increased stillbirth rate remains unknown. Besides other complications, infants of diabetic mothers have long been recognized to be at risk of having hypertrophic cardiomyopathy, a condition that is characterized by thickening of the interventricular septum and ventricular walls, and by systolic and diastolic dysfunction of the neonatal heart. This condition is normally asymptomatic in utero and may only result in congestive heart failure …
Lectin-binding sites in Paget's disease
Authors: K. TAMAKI, H. HINO, K. OHARA, M. FURUE
Journal: British Journal of Dermatology (1985)

Journal Article Lectin‐binding sites in Paget's disease Get access K. TAMAKI, K. TAMAKI Department of Dermatology, University of Tokyo, Tokyo 113, Japan Dr K.Tamaki, Department of Dermatology, Faculty of Medicine, University of Tokyo 7‐3‐1, Hongo, Bunkyo‐ku, Tokyo 113, Japan. Search for other works by this author on: Oxford Academic Google Scholar H. HINO, H. HINO Department of Dermatology, Kanto Central Hospital, 6‐25‐1, Kamiyoga, Setagaya‐ku, Tokyo 158, Japan Search for other works by this author on: Oxford Academic Google Scholar K. OHARA, K. OHARA Department of Dermatology, University of Tokyo, Tokyo 113, Japan Search for other works by this author on: Oxford Academic Google Scholar M. FURUE M. FURUE Department of Dermatology, University of Tokyo, Tokyo 113, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue 1, 1 July 1985, Pages 17–24, https://doi.org/10.1111/j.1365-2133.1985.tb02039.x Published: 01 July 1985 Article history Accepted: 23 November 1984 Published: 01 July 1985
IMMUNOLOGICAL REACTIONS OF PNEUMONIC PLEURAL FLUIDS
Authors: Maxwell Finland
Journal: The Journal of Experimental Medicine (1932)

Pleuritic exudates from patients with lobar pneumonia may be sterile or infected. Sterile fluids, at or about the time of crisis, contain actively acquired antibodies similar to those in the blood serum. Infected fluids do not contain such antibodies, presumably because of the presence in them of large amounts of soluble specific substance. Sterile fluids from patients treated with immune sera have both horse serum and antibodies similar to those injected. Infected fluids from serum-treated cases contain horse serum and such heterologous antibodies as were contained in the therapeutic sera together with homologous soluble specific substance. The concentration of horse serum and antibodies in pneumonic fluids is usually the same or somewhat less than that of the corresponding blood sera.
p70 S6 Kinase Promotes Epithelial to Mesenchymal Transition through Snail Induction in Ovarian Cancer Cells
Authors: Yuen L. Pon, Hong Y. Zhou, Annie N.Y. Cheung, Hextan Y.S. Ngan, Alice S.T. Wong
Journal: Cancer Research (2008)

Abstract p70 S6 kinase (p70S6K) is a downstream effector of phosphatidylinositol 3-kinase and is frequently activated in human ovarian cancer. Here we show that p70S6K functions in epithelial to mesenchymal transition (EMT) responsible for the acquisition of invasiveness during tumor progression. This tumorigenic activity is associated with the ability of p70S6K to repress E-cadherin through the up-regulation of Snail. p70S6K activation induced phenotypic changes consistent with EMT in ovarian cancer cells: The cells lost epithelial cell morphology, acquired fibroblast-like properties, and showed reduced intercellular adhesion. Western blot showed that p70S6K activation led to decreased expression of the epithelial marker E-cadherin and increased expression of mesenchymal markers N-cadherin and vimentin. Inhibition of p70S6K by a specific inhibitor or small interfering RNA reversed the shift of EMT markers. Importantly, p70S6K activation also stimulated the expression of Snail, a repressor of E-cadherin and an inducer of EMT, but not other family members such as Slug. This induction of Snail was regulated at multiple levels by increasing transcription, inhibiting protein degradation, and enhancing nuclear localization of Snail. RNA interference–mediated knockdown of Snail suppressed p70S6K-induced EMT, confirming that the effect was Snail specific. Furthermore, phospho (active)-p70S6K staining correlated with higher tumor grade. We also showed a significant positive correlation between p70S6K activation and Snail expression in ovarian cancer tissues. These results indicate that p70S6K may play a critical role in tumor progression in ovarian cancer through the induction of EMT. Targeting p70S6K may thus be a useful strategy to impede cancer cell invasion and metastasis. [Cancer Res 2008;68(16):6524–32]
425 PROTECTIVE ACTIVITY OF RESVERATROL ON TERT-BUTYLHYDRPEROXIDE AND D-GALACTOSAMINE INDUCED HEPTOCYTE APOPTOSIS AND NECROSIS IN VITRO AND IN VIVO
Authors: H. Farghali, D. Ĉerný, N. Kutinová Canovaá, J. Martínek
Journal: Journal of Hepatology (2008)
Assessment of Double-blindness at the Conclusion of the β-Blocker Heart Attack Trial
Authors: Robert P. Byington
Journal: JAMA (1985)

At the conclusion of a double-blinded, randomized clinical trial of propranolol hydrochloride, but before unblinding, the patients and clinic personnel were asked to guess the treatment group assignment of each patient. While 79.9% of the patients receiving propranolol correctly identified their treatment group assignment, 57.2% of the patients receiving placebo incorrectly guessed that they were also in the propranolol group. No specific mechanism was identified to explain why more patients receiving propranolol were better able to guess their group assignment. Clinic physicians correctly identified the group assignment of 69.9% of the patients receiving propranolol and 68.8% of the patients receiving placebo. Clinic coordinators correctly identified the group assignment of 67.1% of the patients receiving propranolol and 70.6% of the patients receiving placebo. For clinic personnel, heart rate level and heart rate change seem to be the mechanisms employed to identify their patients' treatment assignment.At the conclusion of the Beta-Blocker Heart Attack Trial (BHAT), a major research project sponsored by the National Heart, Lung, and Blood Institute, investigators conducted a survey to assess the effectiveness of the trial's double-blind design. Patients, physicians, and coordinators were asked to guess the treatment group assignment of each subject. Patients receiving the drug, propanolol, were better able to identify their assignment than those receiving a placebo. Clinic personnel were better able than the patients to differentiate between the two groups, probably due to their monitoring of patients' heart rates. The BHAT researchers concluded that, although double-blindness was not completely achieved, this fact did not influence the conduct of the trial, as no group differences in drug and visit compliance or in the use of concomitant therapy were found.
Air pollution: brown skies research.
Authors: A. E. Tattersfield
Journal: Thorax (1996)

<h3>Background</h3> Previous research has shown that home ownership is associated with a reduced risk of admission to institutional care. The extent to which this reflects associations between wealth and health, between wealth and ability to buy in care or increased motivation to avoid admission related to policies on charging is unclear. Taking account of the value of the home, as well as housing tenure, may provide some clarification as to the relative importance of these factors. <h3>Aims</h3> To analyse the probability of admission to residential and nursing home care according to housing tenure and house value. <h3>Methods</h3> Cox regression was used to examine the association between home ownership, house value and risk of care home admissions over 6 years of follow-up among a cohort of 51 619 people aged 65 years or older drawn from the Northern Ireland Longitudinal Study, a representative sample of ≈28% of the population of Northern Ireland. <h3>Results</h3> 4% of the cohort (2138) was admitted during follow-up. Homeowners were less likely than those who rented to be admitted to care homes (HR 0.77, 95% CI 0.70 to 0.85, after adjusting for age, sex, health, living arrangement and urban/rural differences). There was a strong association between house value/tenure and health with those in the highest valued houses having the lowest odds of less than good health or limiting long-term illness. However, there was no difference in probability of admission according to house value; HRs of 0.78 (95% CI 0.67 to 0.90) and 0.81 (95% CI 0.70 to 0.95), respectively, for the lowest and highest value houses compared with renters. <h3>Conclusions</h3> The requirement for people in the UK with capital resources to contribute to their care is a significant disincentive to institutional admission. This may place an additional burden on carers.
80 ROLE FOR PPAR γ IN HEPATIC STEATOSIS AS DETERMINED BY HEPATOCYTE AND KUPFFER CELL-SPECIFIC CONDITIONAL KNOCKOUTS USING CRE RECOMBINASE
Authors: E. Morán-Salvador, M. López-Parra, E. Titos, M. Martínez-Clemente, A. González-Périz, R. Horrillo, C. López-Vicario, Y. Barak, V. Arroyo, J. Claria
Journal: Journal of Hepatology (2010)
Diagnostic Performance of Optical Coherence Tomography Ganglion Cell–Inner Plexiform Layer Thickness Measurements in Early Glaucoma
Authors: Jean-Claude Mwanza, Donald L. Budenz, David G. Godfrey, Arvind Neelakantan, Fouad E. Sayyad, Robert T. Chang, Richard K. Lee
Journal: Ophthalmology (2014)
The lesson of Red Nose Day
Authors: Tony Delamothe
Journal: BMJ (2005)

How do you get the media interested in the health needs of the world's poor? 

T he tsunami that recently devastated South East Asia was a one time natural event that mobilised individuals and eventually governments to donate on an unprecedented scale. But more children have been killed by infectious diseases since 26 December than by the tsunami, an audience in London heard last week. Their deaths have been private events, out of our sight and therefore out of mind.

But money spent on the right things can make a profound difference: for example, in its first five years of operation the Global Alliance for Vaccines and Immunization has saved more than 670 000 lives, by improving …
AN ANTISERUM FOR THE TREATMENT OF TULAREMIA
Authors: LEE FOSHAY
Journal: JAMA (1933)

The antiserum used in these clinical trials was made by inoculating goats subcutaneously with formaldehyde-killed suspensions of Pasteurella tularensis. One batch of serum represented mainly avirulent strains. For all others, virulent strains were used. None of the serum was concentrated or refined. It was cleared by centrifugation or filtration and different samples were treated or used in different ways. Some were preserved with phenol, some were preserved with merthiolate, and some were used without a preservative. Some were used when fresh and others were stored for from three months to one year before using. Dosage has been varied both in amount and in number of injections to determine if possible the general requirements for cases of average severity. Serum has been administered subcutaneously, intramuscularly and, most frequently, intravenously. The diagnosis has been confirmed in each case by agglutination or intradermal tests, frequently by both procedures. The third year's experience with
Good Managed Care Needs Universal Health Insurance
Authors: Donald W. Light
Journal: Annals of Internal Medicine (1999)

Although the increase of corporate managed care has helped to reduce excesses and costs, continued gains in cost-effectiveness depend on good clinically managed care. Benefits of clinically managed care depend on stable contracts and universal coverage. Instead, employers are decreasing coverage and creating a market of "lemons" in which low-cost plans are rewarded for cost-cutting tactics. These tactics have spawned movements that demand rights for patients and providers. Choosing to shore up those rights, however, will increase the number of uninsured persons. This tragic choice, which no other industrialized nation has permitted, will not be resolved until some form of universal health insurance is implemented.
Long-term correction of glycogen storage disease type II with a hybrid Ad-AAV vector
Authors: Bao-dong Sun, Y.-T Chen, Andrew Bird, Andrea Amalfitano, Dwight D Koeberl
Journal: Molecular Therapy (2003)

We administered an adenovirus-adeno-associated virus (Ad-AAV) vector encoding human acid α-glucosidase (hGAA) to acid α-glucosidase-knockout (GAA-KO) mice on day 3 of life by gastrocnemius injection. In contrast to previous results for muscle-targeted Ad vector in adult GAA-KO mice, the muscles of the hindlimb showed reduced glycogen content and persistent hGAA for as long as 6 months after neonatal Ad-AAV vector administration. Not only the injected gastrocnemius muscles, but also the hamstrings and quadriceps muscles produced therapeutic levels of hGAA as a result of widespread transduction with the Ad-AAV vector; moreover, hGAA activity was 50-fold elevated as compared to normal mice. Vector RNA was detected in the hindlimb muscles, the hearts, and the livers by northern blot analysis and/or by RT-PCR for as long as 6 months. The low levels of hGAA detected in the heart were attributable to transduction with the Ad-AAV vector, not to secretion of hGAA by the injected muscle and uptake by the heart. Finally, although an antibody response to hGAA was present, it did not prevent the correction of glycogen storage in the skeletal muscle of GAA-KO mice.
931-114 Effects of Inhibition of Nitric Oxide Synthesis in Proximal and Distal Segments in Patients with Normal Arteries and in Patients with Coronary Artery Disease
Authors: Dimitris Tousoulis, Tom Crake, Costas Tentolouris, David C. Lefroy, John Gialafos, Pavlos Toutouzas, Graham Davies
Journal: Journal of the American College of Cardiology (1995)
Unfair Pressure for Abortion
Authors: H. C. McLaren
Journal: BMJ (1971)

lamines, might be fluctuating hypertensive filling of the atherosclerotic coronary vessels in a usually normotensive or hypertensive person.This may cause the trauma to the arterial wall which sets off changes leading to thrombus formation and cardiac in- farction.Treatment with 13-blocking or hypotensive agents might be used to prevent unnatural rises of blood pressure, level out fluctuations, and thus avoid repeated trauma to the vulnerable vessel wall.Many potential patients are not hypertensive, and a raised blood pressure is therefore not the only reason why this approach should be tried.-Iam, etc., ERIc