tbuckley/cabot-search huggingface dataset:
Detection of Antisense and Ribozyme Accessible Sites on Native mRNAs: Application to NCOA3 mRNA
Authors: Michaela Scherr, Jeanne LeBon, Daniela Castanotto, Heather E. Cunliffe, Paul S. Meltzer, Arnold Ganser, Arthur D. Riggs, John J. Rossi
Journal: Molecular Therapy (2001)

The efficacies of antisense oligonucleotides and ribozymes are greatly dependent on the accessibility of their mRNA targets. Target site accessibility is affected by both RNA structure and the proteins associated along the length of the RNA. To mimic the native state of mRNA for site identification, we have previously used endogenous mRNAs in cellular extracts as targets for defined sequence oligodeoxynucleotides (ODNs) designed to identify both antisense pairing and potential ribozyme cleavage sites. The rationale for this approach is that the specific pairing of an ODN with a mRNA forms a DNA:RNA hybrid that is cleaved by the endogenous RNaseH in the cell extract. To extend the usefulness of this basic approach, we report here the use of semi-random ODN libraries to identify hammerhead ribozyme cleavage sites. Thus, the most accessible sites for antisense and ribozyme base pairing are selected by this approach. A novel feature of the approach described here is the use of terminal transferase-dependent PCR (TDPCR) after reverse transcription to estimate the cleavage efficiency and to precisely determine the RNaseH and ribozyme cleavage sites on mRNAs in cell extracts following treatment with ODN or ribozyme libraries. As a model system, we have targeted the NCOA3 (also known as AIB-1) mRNA in cell extracts. The NCOA3 mRNA encodes a nuclear receptor co-activator that is amplified and over-expressed in a high proportion of breast and ovarian cancers. A highly accessible site on this mRNA was identified, and a ribozyme targeted to this site was demonstrated to effectively downregulate NCOA3 function in cells.
Adiponectin isoforms differentially affect gene expression of rheumatoid arthritis synovial fibroblasts
Authors: K. Frommer, A. Schaffler, C. Buchler, J. Steinmeyer, F. Brentano, S. Gay, U. Muller-Ladner, E. Neumann
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Adipokines are not only produced by adipose tissue. They also play an important role in rheumatoid arthritis (RA), which is associated with increased levels of adipokines in serum, synovial fluid and hyperplastic synovial tissue. We therefore analysed the effects of the adipokine adiponectin and its individual isoforms on the gene expression of RA synovial fibroblasts (RASF). <h3>Methods</h3> Human RASF were stimulated in vitro with adiponectin and analysed for changes in gene expression by Affymetrix oligonucleotide microarrays and protein arrays. Real-time PCR was used to confirm gene expression (mRNA levels) and immunoassays were used to quantify secreted proteins. Media from adiponectin-stimulated RASF were analysed for their chemoattractive potential using a two-chamber migration system. <h3>Results</h3> Stimulation of RASF with adiponectin led to an induction of different genes and proteins including cytokines (eg, protein: IL-6, 45-fold; mRNA: IL-11, 24-fold), chemokines (eg, mRNA: CXCL11, 174-fold; protein: MCP-1, 16-fold), proinflammatory molecules (eg, mRNA: PEG2, 20-fold), growth factors (eg, mRNA: FGF10, 5-fold), adipokines (eg, protein: PBEF1, 6-fold), genes involved in bone metabolism (mRNA: eg, stanniocalcin 1, 20-fold), and matrix-remodeling proteins (eg, protein: pro-MMP-1, 15-fold). Adiponectin induced mRNA/protein expression in both RASF and osteoarthritis synovial fibroblasts (OASF), but the effect on RASF was generally stronger. Adiponectin isoforms had noticeably different potencies for inducing changes in gene and protein expression in RASF. The least potent isoform was the trimeric isoform, while the most potent isoform was either high-molecular weight/middle-molecular weight - enriched adiponectin or globular adiponectin, depending on the parameter of change. Media from adiponectin-stimulated RASF significantly increased the migration of RASF on average by 68%. <h3>Conclusions</h3> Adiponectin strongly affects RASF-dependent inflammation and matrix degradation. The chemoattractive effect shown for RASF potentially contributes to recruitment of additional RASF to the invasion zone. The different potencies observed for the individual adiponectin isoforms imply that targeting specific isoforms or inhibiting the specific receptor binding of isoforms may be of use in therapeutic approaches.
Mesenchymal stromal cells infusions improve refractory chronic graft versus host disease through an increase of CD5+ regulatory B cells producing interleukin 10
Authors: Y Peng, X Chen, Q Liu, X Zhang, K Huang, L Liu, H Li, M Zhou, F Huang, Z Fan, J Sun, Q Liu, M Ke, X Li, Q Zhang, A P Xiang
Journal: Leukemia (2014)
Comparison of Treated and Untreated Severe Histoplasmosis
Authors: Michael L. Furcolow
Journal: JAMA (1963)

Comparison of 194 patients with severe histoplasmosis treated with amphotericin B with a group of 115 untreated patients revealed that adequate dosage with the drug improved prognosis. Inadequate dosage, ie, less than a total of 25 mg/kg of body weight, delayed progression of the disease and decreased the mortality rate temporarily. By the third anniversary of diagnosis, the inadequately treated patients showed little difference from the untreated. However, those with adequately treated chronic pulmonary histoplasmosis showed sustained improvement and lowered mortality rate when compared with the untreated patients. Surgery done when amphotericin B has been given appears safer than surgery without drug coverage. Patients with disseminated involvement, 15% of the total, showed the most dramatic results with treatment. The disease was fatal in 83% of the untreated patients, as contrasted to 23% of the treated patients.
Specialized Care for Elderly Patients
Authors: Edward W. Campion
Journal: New England Journal of Medicine (2002)

Twenty-five years ago, the specialty of geriatrics barely existed in American medicine. There was, however, a growing awareness that increasing numbers of people in developed countries were living into their 80s and 90s. It is now clear that geriatric care can improve outcomes, though not as dramatically as some had hoped. Geriatrics has matured as a specialty. There are numerous training programs, and a certifying board examination has been given for over a decade. Most academic centers now include geriatricians who are involved in research on aging, teaching about clinical care of elderly patients, and delivering care to elderly patients. . . .
Determination of Therapeutic and Toxic Serum Digoxin Concentrations by Radioimmunoassay
Authors: Thomas W. Smith, Vincent P. Butler, Edgar Haber
Journal: New England Journal of Medicine (1969)

A sensitive (0.2 ng per milliliter), precise (standard deviation 3 to 4 per cent), and specific radioimmunoassay for serum digoxin concentration has been developed. Levels are determined by measurement of the extent to which digoxin in the patient's serum competes with tritium-labeled digoxin, added in vitro, for digoxin-specific antibody binding sites. Mean values in nontoxic patients with normal renal function receiving 0.25 or 0.50 mg per day were 1.1 and 1.4 ng per milliliter respectively; the ranges fell within relatively narrow limits. Patients with cardiac arrhythmias attributed to digoxin toxicity had a mean level of 3.3 ng per milliliter, and little overlap with the nontoxic group (p less than 0.001). A determination can be completed in one hour, and may provide useful information to the clinician faced with the difficult problem of evaluating his patient's state of digitalization.
REMOVAL OF SKIN SUTURES
Authors: R. H. Kazmierski
Journal: JAMA (1953)

<h3>To the Editor:—</h3> I enjoyed the article on removal of skin sutures by Weinstein and Roberts inThe Journal, July 25, 1953, page 1231. Dr. Daniel L. Borden introduced a similar traction loop into the suture which he reported in the<i>American Journal of Surgery</i>(<b>73</b>:100, 1947). I have added one more step. I leave the end of the interrupted sutures long and tie the long ends together, or I use a split buckshot in place of the knot so that all stitches can be removed at once. This saves digging around for each stitch and makes it less likely that a stitch will be missed because the light is poor at the bedside, tissue swelling is present, or the area is inaccessible.
More to morality than mutualism: Consistent contributors exist and they can inspire costly generosity in others
Authors: Michael J. Gill, Dominic J. Packer, Jay Van Bavel
Journal: Behavioral and Brain Sciences (2013)

Abstract Studies of economic decision-making have revealed the existence of consistent contributors, who always make contributions to the collective good. It is difficult to understand such behavior in terms of mutualistic motives. Furthermore, consistent contributors can elicit apparently altruistic behavior from others. Therefore, although mutualistic motives are likely an important contributor to moral action, there is more to morality than mutualism.
The Practice of Hand Surgery
Authors: Kingsbury G. Heiple
Journal: JAMA (1989)

This is a generally excellent text that covers the surgical management of disorders affecting the hand in the broadest spectrum from congenital anomalies through arthritis in the elderly as well as the full gamut of reconstructive procedures, procedures addressed at neurological deficits relating to hand dysfunction, and rehabilitation. The fact that this book has gone into an expanded second edition speaks generally well for its acceptance by the surgical community, principally those working on the hand in both the orthopedic and plastic surgery specialties. As is typical with major text efforts of this type today, it has multiple (47) contributors, and it is a tribute to the editors that there is at least a reasonably coherent format and style throughout, even extending to some degree to illustrations and chapter organization. The references are probably as up-to-date (through 1985) as the publishing of a major textbook will allow. This text is
Suppression of growth hormone (GH) secretion by a selective GH-releasing hormone (GHRH) antagonist. Direct evidence for involvement of endogenous GHRH in the generation of GH pulses.
Authors: C A Jaffe, R D Friberg, A L Barkan
Journal: Journal of Clinical Investigation (1993)

To study the potential involvement of growth hormone-releasing hormone (GHRH) in the generation of growth hormone (GH) pulses in humans we have used a competitive antagonist to the GHRH receptor, (N-Ac-Tyr1,D-Arg2)GHRH(1-29)NH2(GHRH-Ant). Six healthy young men were given a bolus injection of GHRH-Ant 400 micrograms/kg body wt or vehicle at 2200 h and nocturnal GH concentrations were assessed by every 10-min blood sampling until 0800 h. Integrated total and pulsatile GH secretion were suppressed during GHRH-Ant treatment by 40 +/- 6 (SE) % and 75 +/- 5%, respectively. GHRH-Ant suppressed maximum (7.6 +/- 2.2 vs 1.8 +/- 0.5 micrograms/liter; P < 0.001) and mean (3.3 +/- 1.0 vs 1.1 +/- 0.2 micrograms/liter; P = 0.02) GH pulse amplitudes. There was no change in integrated nonpulsatile GH levels, pulse frequency, or interpulse GH concentration. GHRH-Ant 400 micrograms/kg also suppressed the GH responses to intravenous boluses of GHRH 0.33 micrograms/kg given 1, 6, 12, and 24 h later by 95, 81, 59, and 4%, respectively. In five healthy men, the responses to 10-fold larger GHRH boluses (3.3 micrograms/kg) were suppressed by 82 and 0%, 1 and 6 h after GHRH-Ant 400 micrograms/kg, respectively. These studies provide the first direct evidence that endogenous GHRH participates in the generation of spontaneous GH pulses in humans.
TCT-675 Prolonged ischemia, detected by intracoronary electrocardiography, after coronary bifurcation stenting predicts adverse events during mid-term follow-up
Authors: Dobrin Vassilev, Alexander Alexandrov, Robert Gil, Slawomir Golebiewski, Hristo Mateev, Pavlin Pavlov, Milena Pehlivanova
Journal: Journal of the American College of Cardiology (2012)
STUDIES ON OPSONINS IN Q FEVER
Authors: Joseph Victor, Ruth Raymond, Jeanne Valliant, John C. Wagner, Abou D. Pollack
Journal: The Journal of Experimental Medicine (1952)

A method was developed for the quantitative determination of opsonins for C. burnetii. An opsonin unit for C. burnetii was defined as that quantity of opsonin which, under standardized conditions, causes phagocytosis of elementary bodies of C. burnetii by 94 to 100 per cent of polymorphonuclear neutrophils. The opsonin titer represents the number of opsonin units in 0.1 ml. of serum or heparinized plasma. A plasma opsonin titer of 1 occurred in 1 per cent of the people tested at Camp Detrick, Frederick, Maryland, with no known contact with C. burnetii; in 30 per cent of the immunized people of Camp Detrick treated by subcutaneous injection of phenol-inactivated C. burnetii in chick embryo yolk sac; and in 31 per cent of the people tested at Los Angeles, with no clinical evidence of Q fever. On a statistical basis, about 42 per cent of the vaccinated people of Camp Detrick and of "normal" Los Angeles people had evidence of increased opsonins in their blood. Vaccinated individuals of Camp Detrick showed no relation between opsonin and complement fixation titers, but individuals living in Los Angeles, an area endemic for Q fever, revealed positive complement fixation tests only in one-seventh of individuals with opsonin titers of 1. The significance of these differences is discussed. The opsonin titer of patients with Q fever may increase many million fold, and much more than the complement fixation titer. The opsonin titers of serum and heparinized plasma were identical, and both decreased with storage at 5 degrees C. The opsonin titer for elementary bodies of C. burnetii grown in chick embryo yolk sac may be used as an epidemiological and diagnostic indicator for the distribution of the agent causing Q fever.
SOME NEW MINNESOTA LAWS ON TUBERCULOSIS
Authors: P. M. HALL
Journal: JAMA (1913)

The discovery of the tubercle bacillus has changed all of our definitions of the disease. The discovery of a specific cure may change many of our methods of control, or our attempts at control. Ultimate control is the aim of all new methods or measures. The last fight against the disease will be made by the public health workers of the world. Changes have occurred both in treatment and in administrative methods; but always there has been progress. The question of control, of prevention rather than cure, naturally appeals to the public health worker. Minnesota has had some legislation on tuberculosis. It has been defined as a contagious and infectious disease and made reportable. A state sanatorium was erected about five years ago. The legislature authorized the appointment of a state advisory commission for this institution. These are some of the things which have been done looking toward control. Two
Cerebral Vascular Diseases. Transactions of the Fourth Conference Held Under the Auspices of the American Neurological Association and the American Heart Association
Authors: Kenneth R. Magee
Journal: JAMA (1965)

Certainly there is no dearth of material discussing cerebrovascular disease. Many journals have recently presented some aspect of the subject, and monographs and symposia considering the problem areabundant. It is a pleasant surprise, therefore, to read a symposium on cerebrovascular disease that contains over 200 pages of well-presented practical information. The remainder of this 271-page work discusses basic studies. The entire book presents an excellent summary of current research and clinical knowledge of cerebrovascular disease. The editors, well-known neurologists at the Mayo Clinic and students of cerebrovascular disease, have assembled experts who present clearly and incisively their studies on particular aspects of the disorder.  Medical and surgical therapy of cerebrovascular disease is considered in detail, together with techniques of diagnosis. The indications for angiography are discussed, as well as contraindications and complications. Recent studies concerning the diagnosis and treatment of subclavian artery occlusive disease and reversal of blood flow in
Potential protective effect of high coronary wedge pressure on left ventricular function after coronary occlusion.
Authors: B de Bruyne, B Meier, L Finci, P Urban, W Rutishauser
Journal: Circulation (1988)

To assess the potential of coronary collateral circulation to protect myocardium after occlusion of a coronary vessel, the mean coronary wedge pressure, the angiographic grade of collateral channels, and the left ventricular function were studied in 47 consecutive patients with mechanical recanalization of totally occluded coronary arteries. Coronary wedge pressure measurements were obtained 39 +/- 51 days (range, 2 hours to 361 days) after the presumed time of occlusion. The patients were divided into two groups: 31 with a coronary wedge pressure more than 30 mm Hg (group 1) and 16 with a coronary wedge pressure of or less than 30 mm Hg (group 2). Patients in group 1 had a significantly higher mean global left ventricular ejection fraction than those in group 2 (63 +/- 9% vs. 49 +/- 7%, p less than 0.001). Regional left ventricular function (artery-related area change) was also superior in group 1 compared with group 2 (47 +/- 11% vs. 36 +/- 10%, p less than 0.01). Global left ventricular function was significantly correlated to coronary wedge pressure (r = 0.51, p less than 0.001) but not to the angiographic presence of collaterals. The data suggest that a high coronary wedge pressure is associated with improved left ventricular function after coronary artery occlusion and that coronary wedge pressure more accurately reflects the physiological role of collaterals than their angiographic presence.
P123 The Use of Indwelling Pleural Catheters For the Management of Non-Malignant Recurrent Pleural Effusions: Abstract P123 Table 1
Authors: R Bhatnagar, ED Reid, JP Corcoran, AO Clive, N Zahan, NM Rahman, S Chatterji, PR Sivasothy, NA Maskell
Journal: Thorax (2012)

Although indwelling pleural catheters (IPC) are commonly used to allow the outpatient management of malignant pleural effusions, an increasing number if IPCs are being inserted to control effusions caused by non-malignant processes. This is the first UK-based series to analyse the use of IPCs in this setting. <h3>Methods</h3> We analysed data from 3 UK hospitals with large pleural services. IPCs inserted between 2007 and June 2012 were identified retrospectively. Information was obtained from hospital records and from patients' primary physicians. Bilateral or non-sequential IPCs in a single patient were treated as separate data points. <h3>Results</h3> 30 IPCs were inserted, with a year-on-year rise in the number of drains seen over the analysis period. The mean age of patients was 64 (range 37–92 years). 57% were male. IPCs stayed in place for a median of 95 days (IQR 41–211) before death or removal. 6 patients died with their IPC in situ. The majority of drains (47%, n=14) were inserted for the management of hepatic hydrothorax of varying aetiology (see table 1). 10 of these patients were given human albumin solution (HAS) intermittently with drainage. 87% of patients began with a drainage frequency of 3 times per week or greater. At final analysis only 37% of patients remained in this group, with 50% overall experiencing a reduction in drainage needs. Drainages were most often performed by community nurses (30%) or family members (30%). Complications included drain site leak (n=1), equipment failure (n=1), pleural infection (n=2) and skin infection (n=1). IPCs were removed in 54% (n=16), with 6 patients achieving successful pleurodesis. Other reasons for removal included fluid loculation (n=2), or transplant operation(n=3). 83% of patients needed no additional pleural intervention following IPC insertion. In only 1 case did the primary physician feel the insertion of the IPC was not of value. <h3>Conclusions</h3> These data suggest the use of IPCs in the non-malignant setting is increasing. Complications were rare and most patients could be managed for extended periods in the community alone. This series would suggest that IPCs are a viable option for the management of recurrent pleural effusions of non-malignant aetiology. Dr Maskell has received an unrestricted research grant from Care Fusion, not related to this study. Dr Rahman acts as a consultant to Rocket Medical UK, not related to this study.
US survey reveals deficits in women's health care
Authors: J. H. Tanne
Journal: BMJ (1999)

A study of women's health in the United States by the Commonwealth Fund, a philanthropic organisation, has indicated worsening health care for poorer women and revealed widespread violence and abuse.

The study, conducted by a national polling organisation, was based on telephone interviews with 2850 women and 1500 men between May and November 1998, who were chosen as a cross section of the population, with an additional over sample of African American, Hispanic, and Asian American women.

Interviewees were asked about access to care, health knowledge and …
Polymyalgia rheumatica and primary biliary cirrhosis.
Authors: J C Robertson, G F Batstone, W Y Loebl
Journal: BMJ (1978)

No significant abnormality could be seen in an electroencephalograph about two weeks after the event, but a right carotid angiograph showed narrowing of a distal branch of the middle cerebral artery in the region of the trifurcation.
Randy L. Jirtle, PhD
Authors: Bridget M. Kuehn
Journal: JAMA (2008)

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The Complementary Role of Environmental and Security Biological Control Regimes in the 21st Century
Authors: Graham S. Pearson
Journal: JAMA (1997)

As we approach the 21st century, there is increased worldwide concern about disease, whether natural or deliberate, in humans, animals, and plants. There are 2 driving forces for multilateral biological control regimes: international/national security and environmental protection. With respect to deliberately caused disease, these seemingly disparate forces are mutually reinforcing as demonstrated by simultaneous moves to strengthen the Biological and Toxin Weapons Convention and the entry into force of the Convention on Biological Diversity. Future multilateral biological control regimes based on these developments will aid the security, prosperity, and health of the world community.