tbuckley/cabot-search huggingface dataset:
178. A Novel RNA Quantitation Method Using Hydrophobic Interaction Chromatography-High Performance Liquid Chromatography
Authors: Shane Johnson, Andrew Doig, Henry Hebel, Hugo Gonzalez, Heather Attra
Journal: Molecular Therapy (2005)

Top of pageAbstract
Advancements have been made in the manufacture of non-viral plasmid-based products. The progression of these products from inception through clinical development has prompted the need for validated assays to evaluate impurities inherent in plasmid production, such as host-cellular RNA. Current quantitative RNA impurity testing methods are time-consuming, complicated and expensive. We have developed a cost-effective, straightforward, easy-to-validate Hydrophobic Interaction Chromatography-High Performance Liquid Chromatography (HIC-HPLC) technique using a non-porous stationary phase that allows for the quantitation of residual host-cellular RNA in the presence of plasmid DNA. Samples are treated with RNase A, which is used to degrade the host-cellular RNA to its free nucleic acid form. Then, a decreasing gradient from ammonium sulfate to water enables the plasmid DNA to be retained by the stationary phase, while allowing the RNased host-cellular RNA to elute at the void volume. This is then compared to an RNased RNA standard curve to determine the quantities of residual RNA present in the samples. Data have shown that interfering void peaks are significantly reduced by preparing samples to the same ammonium sulfate concentration as the initial mobile phase. Based on these assay development studies, we have concluded that this HIC-HPLC RNA quantitation technique accurately, precisely, and reproducibly measures RNA from E. coli-derived plasmid DNA products.
The sicca syndrome in thalassaemia major.
Authors: C Borgna-Pignatti, V Cammareri, P De Stefano, U Magrini
Journal: BMJ (1984)

A 20 year old man with beta thalassaemia developed symptoms of the sicca syndrome. His serum contained rheumatoid factor and antinuclear antibodies. A biopsy specimen of labial salivary gland showed large accumulations of haemosiderin within the parenchymal cells of the acini. Although in this case the sicca syndrome could not be definitely distinguished from Sjögren9s syndrome, the patient9s HLA type was not the one usually associated with Sjögren9s syndrome. Histological appearances suggested that the causative factor of the sicca syndrome was iron overload owing to an intensive blood transfusion regimen.
Whole-genome analysis of mRNA decay in Plasmodium falciparum reveals a global lengthening of mRNA half-life during the intra-erythrocytic development cycle
Authors: Jennifer L Shock, Kael F Fischer, Joseph L DeRisi
Journal: Genome biology (2007)

The rate of mRNA decay is an essential element of post-transcriptional regulation in all organisms. Previously, studies in several organisms found that the specific half-life of each mRNA is precisely related to its physiologic role, and plays an important role in determining levels of gene expression. We used a genome-wide approach to characterize mRNA decay in Plasmodium falciparum. We found that, globally, rates of mRNA decay increase dramatically during the asexual intra-erythrocytic developmental cycle. During the ring stage of the cycle, the average mRNA half-life was 9.5 min, but this was extended to an average of 65 min during the late schizont stage of development. Thus, a major determinant of mRNA decay rate appears to be linked to the stage of intra-erythrocytic development. Furthermore, we found specific variations in decay patterns superimposed upon the dominant trend of progressive half-life lengthening. These variations in decay pattern were frequently enriched for genes with specific cellular functions or processes. Elucidation of Plasmodium mRNA decay rates provides a key element for deciphering mechanisms of genetic control in this parasite, by complementing and extending previous mRNA abundance studies. Our results indicate that progressive stage-dependent decreases in mRNA decay rate function are a major determinant of mRNA accumulation during the schizont stage of intra-erythrocytic development. This type of genome-wide change in mRNA decay rate has not been observed in any other organism to date, and indicates that post-transcriptional regulation may be the dominant mechanism of gene regulation in P. falciparum.
Accidental Exposure to Ethylenimine and N-Ethylethylenimine Vapors
Authors: Joseph Weightman, J. Preston Hoyle
Journal: JAMA (1964)

Five college students in Lewisburg, Pa, were accidentally exposed to two highly toxic chemicals, ethylenimine and N-ethylethylenimine, for two hours in a poorly ventilated fraternity-house room. Their complaints, delayed in onset from 3 to 71/2 hours after exposure, were severe soreness of the throat, severe eye irritation, vomiting, and coughing. Consistent clinical findings were conjunctivitis, upper and lower respiratory tract inflammation, transitory polycythemia, leukocytosis, eosinophilia, and albuminuria. Treatment included antihistamines, hydration, topical and systemic steroids, antibiotics, cough preparations, and enzyme therapy. All five students were free of symptoms within six months.
Long-term survival after cadaveric renal transplantation.
Authors: E Savdie, J F Mahony, R J Caterson, J H Stewart, S Etheredge, B G Storey, A G Sheil
Journal: BMJ (1982)

In a series of 404 consecutive first cadaver kidney transplants performed since 1967 the actuarial five- and 10-year survival of patients were 61% and 47% respectively and of grafts 46% and 36%. In more than four-fifths of the patients surviving these intervals the original cadaveric grafts were functioning at these times, and most of the remainder were sustained by subsequent grafts. Although graft survival has remained static since 1967, patient survival improved. Results for 43 consecutive second cadaver transplants were similar after five years to those of first grafts. These results promote the acceptability of cadaveric transplantation as a long-term treatment for chronic renal failure.
Prednisone withdrawal advocates: Beware of recurrent autoimmune hepatitis
Authors: Rene Davila, Emmet B. Keeffe
Journal: Hepatology (1999)

Background.Recurrence of autoimmune hepatitis after liver transplantation is not rare, but there is little information about its time of onset, risk factors, response to treatment and prognosis.The aim of this study was to evaluate the rate of recurrence and outcome of autoimmune hepatitis after transplantation.Methods.The records of patients transplanted in eight centers in our country between 1984 and 1996 were retrospectively analyzed.Results.Forty-three of the 2331 (1.8%) recipients fulfilled diagnostic criteria of autoimmune hepatitis at the time of transplantation.Sixteen patients were excluded from evaluation.Nine (33%) of the 27 patients evaluated fulfilled criteria for recurrence of autoimmune hepatitis, with a mean time of recurrence after orthotopic liver transplantation of 2.6 ؎ 1.5 years.Patients with recurrence had a longer follow-up time after transplantation (5.1 vs. 2.5 years, P ‫؍‬ 0.0012) and were receiving less immunosuppressive treatment.The estimated risk of recurrence of autoimmune hepatitis in the graft increased over time: 8% over the first year and 68% 5 years after transplantation.None of the seven patients with liver-kidney microsomal-positive antibodies recurred (P ‫؍‬ 0.059).Fifty percent of the patients failed to respond or responded only partially to therapy, although none of the patients have deteriorated clinically after 2.4 ؎ 1.06 years of follow-up after recurrence.Conclusions.Recurrence of autoimmune hepatitis in the graft is a common event with an incidence that increases over time as immunosuppression is reduced.Although response to treatment is poor, patient and graft survival do not appear to be decreased.
The Internist as Gatekeeper
Authors: JOHN M. EISENBERG
Journal: Annals of Internal Medicine (1985)

To reduce health care costs, some third-party payors have enlisted primary care physicians as gatekeepers to medical care. In gatekeeper systems, primary care physicians must approve all care provided to their patients. This approval is a condition of payment for the service, with the usual exception of true emergencies. The gatekeeper approach, sometimes called the case-manager plan, extends the responsibility of primary care physicians from coordination to control of medical care. However, for the plan to stimulate cost-effective medical care, it must overcome obstacles that threaten its ability to save money and provide high-quality medical care. If internists are to serve as gatekeepers, then medical educators must ensure that the necessary attitudes, skills, and knowledge are taught to students of internal medicine.
SEPIAPTERIN INHIBITS ADAPTIVE LEFT VENTRICULAR HYPERTROPHY BUT PREVENTS DILATORY REMODELING INDUCED BY PRESSURE OVERLOAD IN RATS
Authors: Kei Yoshioka, Hajime Otani, Takayuki Shimazu, Masanori Fujita, Toru Okazaki, Daisuke Sato, Toshiji IwasakA
Journal: Journal of the American College of Cardiology (2011)
Letter from Chicago: Joe Doe's new year
Authors: G. Dunea
Journal: BMJ (1991)

have met this bunch of extraverts who keep drifting off, arms round shoulders, murmuring "Do you remember that ward round with old what's his name?"The first full day should include the postgraduate meeting.This should read well on the programme but be short and stimulating.Ideally the presentations should be by year members on their own specialties or interests.A number of group activities might follow on from this, such as a treasure hunt, clay pigeon shooting, and of course a year photograph.These all precede the reunion dinner, which is after all the raison d'etre.The reunion dinner will include the inevitable toasts but once these are out of the way, the organising committee should be able to relax and enjoy a good meal, good company, and a good band.If the band can be persuaded to play contemporary music from your student days to get everyone on to their feet and in the mood then the event should go with a swing.Just when you have got yourself, and everyone else, into the right time frame, when old friendships have been renewed and gossip exchanged, the reunion dinner will be drawing to a close.On the morning after, for those still lingering on, ensure there is some lively music to offset the inevitable sad farewells.Successfully organising a reunion of classmates takes time and energy.It should be approached with care and attention to detail, with important tasks delegated to members of an enthusiastic committee.Leafing through a copy of the year book will provide another 10 years of nostalgia and make the effort all seem worth while.
Laboratory Studies on Rubella and the Rubella Syndrome
Authors: S. A. Plotkin, J. A. Dudgeon, A. M. Ramsay
Journal: BMJ (1963)

RUBELLAMwDI.ouuL -~~~~~~~~~~~~~~~~~~~~~~~~~~~~~MXA ORA rubella rash has nothing of the blotchy appearance of a well- developed measles eruption, while the brilliant phenomenon of " staining " so characteristic of measles is unlikely to occur in rubella unless the rash is of exceptional severity.Table IV shows the incidence of physical signs in 114 patients with rubella seen in 1962.TABLE IV.-Incidence of Physical Signs In 114 Patients With Rubella (1962) Injection of tonsillo-pharyngeal area No. of Patients Without discomfort.80-94' With 27 Absent.7 Glandular enlargement Posterior cervical and suboccipital .. 78 Generalized only .1697% G~eneralized .. .. .. .
Inflammatory joint disease: a comparison of liposome scanning, bone scanning, and radiography.
Authors: M M O'Sullivan, N Powell, A P French, K E Williams, J R Morgan, B D Williams
Journal: Annals of the Rheumatic Diseases (1988)

Patients with rheumatoid arthritis, psoriatic arthritis, and osteoarthritis were assessed by clinical evaluation, radiography, and joint scintigraphy using technetium labelled methylene diphosphonate (MDP) and technetium labelled liposomes. Although both scanning techniques were more sensitive than radiographs in detecting joint disease, the liposomes scans were positive only in clinically active inflammatory disease. In patients with rheumatoid arthritis liposome scintigraphy was also able to discriminate between different grades of joint tenderness. In inactive inflammatory polyarthropathies, although the MDP bone scans continued to show increased activity, the liposome scans did not and were therefore a more accurate reflection of the clinical state. The increased uptake in the liposome scans may be due to incorporation of the liposomes into the phagocytic cells of the synovium. This scan may, therefore, by reflecting the activity of cells involved in the disease process, provide a useful way of assessing disease activity and progression.
Adverse effect of plasma exchange on anti-D production in rhesus immunisation owing to removal of inhibitory factors.
Authors: G R Barclay, M A Greiss, S J Urbaniak
Journal: BMJ (1980)

Intensive plasma exchange was used to reduce the maternal anti-D concentration in case of severe rhesus haemolytic disease. Initially the concentration fell from 30 to 4 IU/ml, but after six exchanges it increased to 490 IU/ml despite continued exchanges, and intrauterine fetal death eventually ensued. The increase in the rate of maternal anti-D production coincided with, and may have resulted from, removal of plasma immuno-regulatory factors that inhibited in-vitro lymphocyte functions. These results that the role of plasma exchange in haemolytic disease of the newborn is more complex than simply removing the antibody and that further investigations are needed.
Interaction of the Onset of Spring and Elevated Atmospheric CO <sub>2</sub> on Ragweed ( <i>Ambrosia artemisiifolia</i> L.) Pollen Production
Authors: Christine A. Rogers, Peter M. Wayne, Eric A. Macklin, Michael L. Muilenberg, Christopher J. Wagner, Paul R. Epstein, Fakhri A. Bazzaz
Journal: Environmental Health Perspectives (2006)

Increasing atmospheric carbon dioxide is responsible for climate changes that are having widespread effects on biological systems. One of the clearest changes is earlier onset of spring and lengthening of the growing season. We designed the present study to examine the interactive effects of timing of dormancy release of seeds with low and high atmospheric CO2 on biomass, reproduction, and phenology in ragweed plants (Ambrosia artemisiifolia L.), which produce highly allergenic pollen. We released ragweed seeds from dormancy at three 15-day intervals and grew plants in climate-controlled glasshouses at either ambient or 700-ppm CO2 concentrations, placing open-top bags over inflorescences to capture pollen. Measurements of plant height and weight; inflorescence number, weight, and length; and days to anthesis and anthesis date were made on each plant, and whole-plant pollen productivity was estimated from an allometric-based model. Timing and CO2 interacted to influence pollen production. At ambient CO2 levels, the earlier cohort acquired a greater biomass, a higher average weight per inflorescence, and a larger number of inflorescences; flowered earlier; and had 54.8% greater pollen production than did the latest cohort. At high CO2 levels, plants showed greater biomass and reproductive effort compared with those in ambient CO2 but only for later cohorts. In the early cohort, pollen production was similar under ambient and high CO2, but in the middle and late cohorts, high CO2 increased pollen production by 32% and 55%, respectively, compared with ambient CO2 levels. Overall, ragweed pollen production can be expected to increase significantly under predicted future climate conditions.
Role of connective tissue proteases in the pathogenesis of chronic inflammatory lung disease.
Authors: J E Gadek, G A Fells, R L Zimmerman, R G Crystal
Journal: Environmental Health Perspectives (1984)

The normal structure and function of the human lung is dependent on the maintenance of the connective tissue matrix. These structural macromolecules provide the template for normal parenchymal cell architecture on which efficient gas exchange depends. In addition, the organization and amount of this extracellular matrix accounts for much of the mechanical behavior of the lung parenchyma during the respiratory cycle. The preservation of this intricate connective tissue scaffold depends on the lung's capacity to prevent enzymatic disruption of the component matrix proteins. Specifically, the integrity of the normal connective tissue skeleton of the lung is determined by the maintenance of a balance between proteases capable of cleaving these structural elements and the specific protease inhibitors. The normal extracellular matrix is preserved when the local concentrations of protease inhibitors prohibits expression of active connective tissue proteases within the lung parenchyma. Conversely, the disruption of lung structure during the course of acute and chronic inflammatory diseases of the lung is often associated with an imbalance of protease-antiprotease activity. The consequence is the expression of unimpeded proteolytic attack on the connective tissue matrix of the lung. In this context, the nature of the pulmonary lesion and its physiologic consequences, reflect the specificity of the expressed proteases for the individual connective tissue components. Experimental evidence suggests that the differential expression of collagenase and elastase, prototypes of connective tissue proteases, may determine whether the pathologic outcome is fibrosis (e.g., idiopathic pulmonary fibrosis) or destruction (e.g., emphysema) of the alveolar structures.
MECHANISM OF EOSINOPHILIA
Authors: Antony Basten, Markley H. Boyer, Paul B. Beeson
Journal: The Journal of Experimental Medicine (1970)

The phenomenon of eosinophilia was studied in rats using inoculation with Trichinella larvae as the experimental stimulus. Comparisons were made between the eosinophil response accompanying active infestation via the gastrointestinal tract and that resulting from parenteral inoculation of larvae or their products. A vigorous eosinophilia could be provoked by a single intravenous injection of intact parasites. In this circumstance the larvae lodged in the lungs causing an acute inflammatory reaction which led to their disintegration within 24 hr. Intraaortic injection also produced a significant response, whereas inoculation of the same number of parasites by the intramuscular, intraperitoneal, or subcutaneous routes did not cause eosinophilia. Eosinophilia likewise failed to develop if parasites were homogenized before intravenous injection, so that they were not arrested in the lungs. Antibody levels, as measured by a hemagglutination technique, using whole larval extract as antigen, did not correlate closely with the eosinophil response. The findings are interpreted as suggesting that increased eosinophil production is induced under some circumstances as a consequence of interaction between intact parasites and certain host cells in blood and tissue. No evidence was found for the existence of a specific constituent of the parasite capable of stimulating eosinophil production. Attention is directed to features of eosinophilia which fit with the concept that this phenomenon belongs in the category of immunologic reactions.
A comparative analysis of the C1-binding ability of fragments derived from complement-fixing and noncomplement-fixing IgM proteins.
Authors: M M Hurst, J E Volanakis, R M Stroud, J C Bennett
Journal: Journal of Clinical Investigation (1976)

The purpose of this study was to examine the molecular parameters necessary for initiation of complement fixation by IgM proteins. To determine why some IgM molecules are capable of complement fixation while others are not, several different Waldenström IgM proteins were examined for their ability to fix total hemolytic complement in the CH(50) assay. Subsequently, the C1 fixing ability of a 56-residue fragment derived from the Cmu4 domain of each of these IgM molecules was studied with C1 fixation assay. One of the three Waldenström IgM proteins (Gr) used in the present study was found unable to consume complement in a CH(50) assay when tested at the same concentration as the two complement-consuming IgM molecules (Dau and Bus). However, when the 56-residue C(H)4 fragment from the Cmu4 domain of each IgM molecule was tested for C1-fixing ability, all three were found to bind C1. On the basis of these observations, it is proposed that a C1 binding site exists within the Cmu4 domain of both complement-fixing and noncomplement-fixing IgM molecules. Presumably, the latter molecules are unable to interact in their native state with C1 in the manner required for initiation of the classical complement pathway, possibly due to the configurational inaccessibility of the entire C1 binding site.
Blalock-Taussig Shunt for Tetralogy of Fallot in a Patient With Sickle Cell Anemia
Authors: James D. O'Keefe
Journal: JAMA (1967)

SIGNIFICANT congenital heart disease in patients with sickle cell anemia has rarely been reported.<sup>1,2</sup>Sickle cell anemia is particularly significant in patients who have cyanotic congenital heart disease because they cannot increase their red blood cell and hemoglobin levels to compensate for the hypoxemia. Rudolph et al<sup>3</sup>have shown that correction of iron deficiency anemia in cyanotic patients improves their performance and lessens symptoms. This is a case report of a 4-year-old Negro boy with sickle cell anemia and tetralogy of Fallot who underwent a Blalock-Taussig shunt operation with distinct improvement in his cardiac symptoms. <h3>Report of a Case</h3> This patient's birth on Aug 15, 1961, was uneventful, and he was asymptomatic until the age of 2 months. He then developed syncope, but no cyanosis or other cardiac symptoms were noted until the age of 18 months. Numerous hospitalizations were then required for diarrhea and anemia, and he
Nature's Experimental Models
Authors: Samuel Vaisrub
Journal: JAMA (1976)

It is a pity that no experimental studies were being done when the earth was young and twins such as Castor and Pollux could boast of having two fathers, one human and one divine. Bipaternal twins are here no more, and we must make do with available monozygotic (identical) and dizygotic (fraternal) pairs. Still, despite these limitations, twins are becoming increasingly important as experimental models. Differences between identical and fraternal twins, between twins and nontwins, between identical twins who have a specific trait or disease and those who do not—all are providing clues to the separation of "nature" from "nurture." For example, a recent study by McIlhany et al<sup>1</sup>of blood pressure response to the cold pressor test in 200 pairs of twins demonstrated greater variance in basal and response levels between the fraternal than the identical co-twins. Since the latter differ only in their environment whereas the former
Study of community-acquired pneumonia: Incidence, patterns of care, and outcomes in primary and hospital care
Authors: Alberto Capelastegui, Pedro P. España, Amaia Bilbao, Julio Gamazo, Federico Medel, Juan Salgado, Iñaki Gorostiaga, Cristobal Esteban, Lander Altube, Inmaculada Gorordo, Jose M. Quintana
Journal: Journal of Infection (2010)