tbuckley/cabot-search huggingface dataset:
95. Transduction and Expression of shRNAs Via Lentiviral Bectors Bearing a U6 RNA Polymerase III Promoter, but Not an H1 Promoter, Induce Elevated Apoptosis in Human Primary Peripheral Blood T Lymphocytes
Authors: Dong Sung An, Xiao-Feng Qin, Si-Hua Mao, Vincent C. Auyeung, David Baltimore, Irvin S.Y. Chen
Journal: Molecular Therapy (2005)

Potent, stable and long term siRNA-mediated gene silencing is crucial for successful application of the RNAi technology to therapeutic interventions. We examined effects of shRNA expression in human primary peripheral blood T lymphocytes (PBLs) using lentiviral vectors bearing either a human H1 or a U6 promoter. We found that the U6 promoter is 8 fold more potent than the H1 promoter in driving the expression of shRNA measured by Northern blot analysis and 4 fold more potent for reducing cell surface expression of human CCR5 in PBLs by FACS analysis. However, the shRNA expression from the U6 promoter resulted in reduction of productively transduced PBL populations marked by GFP. We found that the U6 promoter driven shRNA expression caused elevated apoptosis in shRNA transduced primary PBLs. We observed 2-4 fold higher level of the Annexin V positive population in the U6 promoter vector transduced PBLs than the H1 promoter vector transduced PBLs. In contrast to the vectors with U6 promoter, stable maintenance of the shRNA transduced PBLs was obtained by the H1 promoter driven shRNA lentiviral vectors without cytopathic effects. We also examined up-regulation of interferon responsive genes such as OAS1 and ISG15 and the up-regulation of the genes was not evident in the shRNA transduced PBLs. Despite the cytopathic effects, the vector transduced T lymphocytes responded to PMA and Ionomycin and produced interferon |[gamma]| normally. Our results show that high levels of shRNA expression are not necessary for effective inhibition of cellular target genes when a potent shRNA is chosen. Instead a lower level of shRNA expression may be advantageous to maintain a stably transduced population. Thus, lentivral vectors bearing the H1 promoter are more suitable for stable transduction and expression of shRNA in primary human PBLs. ShRNA transduced cells should be carefully monitored using multiple functional assessments.
When is Helicobacter pylori infection acquired?
Authors: D J Cullen, B J Collins, K J Christiansen, J Epis, J R Warren, I Surveyor, K J Cullen
Journal: Gut (1993)

Cross sectional surveys have shown an increasing prevalence of Helicobacter pylori (H pylori) infection with increasing age in Western populations. The aim of this study was to examine the pattern of acquisition of H pylori infection over a 21 year period in a group of 141 adults who had blood samples and serum stored in 1969, 1978, and 1990. A prevalence of H pylori antibody of 39% in 1969 serum samples, 40.9% in 1978, and 34.8% in 1990 was found when assessed by an enzyme linked immunosorbent assay (ELISA). Of the 86 subjects who were seronegative in 1969, only six (7%) were seropositive in 1990. These data suggest that a cohort effect may contribute to the pattern of increasing prevalence of H pylori infection seen with increasing age. Acquisition of infection in adults is rare. It is unlikely, therefore, that reinfection will occur after successful eradication.
Zoledronic acid increases bone density but does not reduce fractures in frail elderly people, study finds
Authors: Z. Kmietowicz
Journal: BMJ (2015)

A single intravenous dose of the osteoporosis drug zoledronic acid has been found to increase bone mineral density in a group of frail elderly women living in nursing homes and long term care facilities, but it did not reduce the incidence of fractures over a two year period.

Researchers from the University of Pittsburgh found that 85% of elderly people in long term care facilities had osteoporosis and fracture rates eight to nine times higher …
Points from letters: Arthroscopy of the knee
Authors: D J Stoker
Journal: BMJ (1977)

should be deprived of benefit from their husbands' war service.Interest at 3-50o compound, without tax relief, payable to secure war service pension compares very unfavourably with the miserable 210O simple-taxable-paid since 1948 on our compensation for loss of goodwill.A colleague of mine with six years of war service recently wrote to the appropriate department of the Ministry of Defence seeking confirmation of the dates of his war service.I understand th'at the reply
p53 and cancer therapy: a double-edged sword
Authors: Gaël McGill, David E. Fisher
Journal: Journal of Clinical Investigation (1999)

When misexpression of the Myc oncoprotein was found to produce enhanced susceptibility to apoptosis (1), it suggested that disabling death may be a fundamental component of neoplastic transformation. It also raised the hope that rekindling such death susceptibility may revert the cancer cell to a hypersensitive state amenable to cure. One of the chief regulators of apoptosis in malignancy is p53, also thought to be the most commonly mutated gene in human cancer.
Reduced calcium currents in subendocardial Purkinje myocytes that survive in the 24- and 48-hour infarcted heart.
Authors: P A Boyden, J M Pinto
Journal: Circulation (1994)

BACKGROUND The abnormal transmembrane action potentials of subendocardial Purkinje fibers that survive 24 to 48 hours after coronary artery occlusion can be a source of the multiform ventricular tachycardias that occur during this time. A change in the density or function of either or both the T-type and L-type cardiac Ca2+ channels may contribute to the altered electrical activity of these Purkinje myocytes. METHODS AND RESULTS The purpose of this study was to determine the function of the T- and L-type Ca2+ currents (iCat and iCaL, respectively) in Purkinje myocytes dispersed from the subendocardium of the left ventricle 24 and 48 hours after coronary artery occlusion (IZPC24 and IZPC48, respectively). To do this we compared whole-cell Ca2+ currents from Purkinje myocytes enzymatically dispersed from free-running fiber bundles (SPCs), from the subendocardium of the noninfarcted canine heart (NZPCs), and from IZPC24 and IZPC48. ICaL and iCat were recorded with Cs(+)- and EGTA-rich pipettes and in Na(+)-K(+)-free external solutions to eliminate overlapping currents. ICaL density was significantly reduced in IZPC48 compared with NZPC or IZPC24. This was not accompanied by a shift in the current-voltage relation or by a change in the time course of decay of iCaL. Replacement of Ca2+ with equimolar Ba2+ increased iCaL density in all cell types, but peak iBaL of IZPC48 remained reduced compared with control iBaL values. T-type Ca2+ currents were recorded in all SPCs and NZPCs. In IZPC24 and IZPC48 there was a reduction in peak iCat amplitudes and densities. This was not accompanied by a shift in the current-voltage relation or by a change in the time course of decay of peak iCat. However, there was a hyperpolarizing shift in the steady-state availability relations in both IZPC24 and IZPC48. In addition, the maximally available iCat in IZPC24 was not different from control, whereas it was significantly reduced in IZPC48. CONCLUSIONS The L-type ICa density in subendocardial Purkinje myocytes that survive in the infarcted heart is significantly decreased by 48 hours after the time of coronary artery occlusion. The peak T-type ICa density is decreased in subendocardial Purkinje myocytes that survive in the infarcted heart at 24 hours, but further reduction occurs in these myocytes by 48 hours. This loss in Ca2+ channel function could contribute to the abnormal transmembrane potentials of these myocytes surviving in the infarcted heart.
Drug induced alterations in dreaming: An exploration of the dream data terrain outside activation-synthesis
Authors: Jim F. Pagel
Journal: Behavioral and Brain Sciences (2004)

Two meta-analyses of pharmacological research are presented, demonstrating that psychoactive drugs have consistent effects on EEG and sleep outside of their effects on REM sleep, and demonstrating that drugs other than those affecting sleep neurotransmitter systems and REM sleep can also alter reported nightmare occurrence. These data suggest that the neurobiology data terrain outside activation-synthesis may include sleep and dream electrophysiology, cognitive reports of dreaming, effects of alterations in consciousness on dreaming, immunology and host defense, and clinical therapies for sleep disorders.
Deprivation and late presentation of glaucoma: case-control study
Authors: S. Fraser
Journal: BMJ (2001)

To identify socioeconomic risk factors for first presentation advanced glaucomatous visual field loss.Hospital based case-control study with prospective identification of patients.Three hospital eye departments.Consecutive patients newly diagnosed with glaucoma (n=220). Cases (late presenters) were those presenting with advanced glaucoma (n=110), controls were those with early glaucoma (n=110).Median underprivileged area scores were higher among late presenters (29.5; interquartile range 9.0-42.2) than in the control group (21.3; 6.1-37.4) (P=0.035). Late presenters were more likely to be of lower occupational class (odds ratio adjusted for age and referral centre 20.1 (95% confidence interval 2.6 to 155) for group III compared with group I-II and 86.0 (11.0 to 673 for group IV-V compared with group I-II), to have no access to a car (2.2; 1.2 to 4.0), to have left full time education at age 14 or less (7.5; 2.3 to 24.7), and to be tenants rather than owner occupiers (local authority tenants 3.2; 1.7 to 5.8, private tenants 2.1; 0.7 to 5.8). Effects of deprivation were partly accounted for by family history of glaucoma, time since last visit to an optometrist, and lack of an initial diagnosis of glaucoma by an optometrist.Area and individual level deprivation were both associated with late presentation of glaucoma. Existing evidence shows that late presentation is an important risk factor for subsequent blindness. Deprived groups thus seem to be at greater risk of going blind from glaucoma. Material deprivation may be associated with more aggressive disease as well as later presentation.
Inpatient and Outpatient Long-Term Psychotherapy of Patients Suffering from Factitious Disorders
Authors: Reinhard Plassmann
Journal: Psychotherapy and Psychosomatics (1994)

A favorable therapeutic course is achieved by the combination of an initial clinical psychotherapy and a subsequent analytical long-term treatment implemented as an outpatient therapy or an interval therapy. This form of therapy was offered to all of the patients and was accepted by half of the patient collective, i.e., by 12 out of 24. Only in 1 of these 12 cases, was it possible to dispense with the initial clinical therapy in favor of a primary outpatient therapy. Of these 12 therapies, 2 were terminated by the patients. We were able to continue the other 10 for longer periods, extending up to 4 years. In this setting, a transition from the working phase to the separation phase is possible around the fourth year of therapy. Termination of therapy is almost always based on a negative therapeutic reaction. The patients were generally capable of development, but were not able to take advantage of this opportunity because of the dominance of malignant introjects. In several cases, this pattern has become consolidated on a social as well as an endopsychic level. The therapy is then terminated in favor of a structured mother-child relationship or a similarly structured marriage. In those cases where the therapy was broken off prematurely, the establishment of a sufficiently stable working relationship was prevented by the predominantly negative transference. As a result, it was not possible to conduct a follow-up therapy after the normal end of the clinical psychotherapy, for example. The question remains whether a significant lengthening of the clinical psychotherapy could have changed anything here; in my opinion, this is not the case. In these cases, the inpatient therapy was always terminated by the patients, either by a directly expressed wish or by a symptomatic development making referral or discharge imperative. The 10 cases undergoing long-term therapy all progressed favorably, with a significant, or at least marked, improvement of the symptomatology and the relationship capability. In this context, the results are, in each case, a function of the severity of the illness, the individual capability for growth, and the length of treatment. Even though 6 of the 10 long-term therapies are now in the separation phase, none of them has been finally ended yet. As a result, we have only a small amount of information so far on the possibilities for reaching a final conclusion of the therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
Importance of Both Allergen-Specific (ANR) and Non-Specific Nasal Reactivity (NNR) in the Development of Early- and Late-Phase Nasal Responses
Authors: S. Miyahara, N. Miyahara, S. Matsubara, A. Joetham, E.W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2007)
Oxidatively modified LDL contains phospholipids with platelet-activating factor-like activity and stimulates the growth of smooth muscle cells.
Authors: J M Heery, M Kozak, D M Stafforini, D A Jones, G A Zimmerman, T M McIntyre, S M Prescott
Journal: Journal of Clinical Investigation (1995)

Oxidative modification of lipoproteins is believed to be important in the genesis of atherosclerosis. We established cultures of smooth muscle cells (SMC) and exposed them to native LDL or oxidized LDL. Oxidized LDL, but not native LDL, was mitogenic as measured by incorporation of [3H]-thymidine into DNA. This effect was concentration dependent, averaged 288% of control, and was blocked by a platelet-activating factor (PAF) receptor antagonist. We hypothesized that phospholipids with PAF-like activity were generated during the oxidation of LDL. To test this hypothesis we extracted phospholipids from copper-oxidized LDL and assayed for PAF-like activity. Phospholipids extracted from oxidized LDL and purified by HPLC induced neutrophil adhesion equivalent to PAF (10 nM) and were mitogenic for smooth muscle cells. These effects were not seen with phospholipids extracted from native LDL and were blocked by two structurally different, competitive antagonists of the PAF receptor. The effects of these lipids were also abolished by pretreating them with PAF acetylhydrolase. Finally, we used Chinese hamster ovary cells that had seen stably transfected with a cDNA for the PAF receptor to confirm that phospholipids from oxidized LDL act via this receptor. We found that PAF (control) and the oxidized phospholipids each induced release of arachidonic acid from the transfected cells, but had no effect on wildtype Chinese hamster ovary cells, which lack the PAF receptor. This effect was also blocked by a PAF receptor antagonist. Thus, phospholipids generated during oxidative modification of LDL may participate in atherosclerosis by stimulating SMC proliferation and leukocyte activation.
Excerpts FROM THE FITZPATRICK LECTURES: Delivered before the Royal College of Physicians of London, November, 1918
Authors: A. Chaplin
Journal: BMJ (1918)

THE early history of the Army Medical Service is some- what obscure and difficult to follow.But the germ of the system is to be found-,at any rate, so far as regards its control-in the practice which obtained from early times of apppinting a physician and .asurgeon to accompany the monarch or the commander-in-chief when he went to the war.Naturally the men were appealed to by the com- mander in any medical difficulty that arose, and soon, in addition.to being responsible.forthe health of its head, they were.saddled -with., the additional care of the health of.thearmy.One of the first.appointments in this capacity.was that.-of Thomas.Musffett, who accompanied the Earl of Essex to .Normandy in 1591.During the Civil -War a serious attempt was made to place the medical department of the army under proper supervision, and: to -this end the Parliament ordered three physicians, one ot whom was Paul de Laune, to be attached to the army under the command of the Earl of Essex.The commission.lists of the Cavaliers.and-theRoundheads also show that to each regiment a regular surgqon was attached.In 1649 a further= step .wastaken, and Jonathan Goddard was appointed by Cromwell to the post of "first p)iysician" to. the army..In this capacity: Goddard accompanied Cromwell to Scotland and Ireland, wlhere he was suc- ceeded by Sir William Petty in 1652.The position of a singje,medical head,in supreme authority over medical matters in the army was thus established, and a surgeon came to exercise supervision over surgeons.At first these chief physicians and surgeons held their appointments only during a war; but in 1660, when a standing army was authorized, a physiciangeneral and. a surgeon-general were appointed who exercised authority continuously during peace and war.The first physician-general was Thoia Laurence-in 1685, and the first surgeon-general was John Knight in 1664.Physicians and surgeons- general.were also appointed for Scotland.and, Ireland, and from 1660 until 1756 na material change was.made in the method, of government of the medical department in the ar-my..Acqording. to Richlard Brocklesbyf the first attempt to, form an Army Medical Board of Control was made kv-17Sby the Duke of Cumberland, who desired Viscount BanirAogton,.Secretary of State for War, to establish a- hoqpi4al board for the army.The board was composed .of the Physician-General, the Surgeon-General, the PhysiWians to Hospitals, the Principal Surgeon of Hos- pitals, and the PurveyorOGeneral.The board recom- mnmeded thalt the physicians slhould examine, superintend, and control the hospital mates, but that the.surgeons -hould be allowed to nominate.mates for their own depart- ment.Much was expected, from the deliberations of the board,.but its career was suddenly cut short by the outbreaek.of war, when the. physicians to hospitals and most of the surgeons were .sentabroad, and, the Principal Hospital Surgeon, after having been appointed Inspector .ofRegimental Infirmaries, gradually
Role of Liver in Glucose Homeostasis
Authors: Robert S Sherwin
Journal: Diabetes Care (1980)

The liver has a unique role in regulation of blood glucose in the postabsorptive state, after ingestion of glucose-containing meals, and in circumstances of glucopenia. It is soley responsible for the delivery of glucose to the bloodstream in the fasted state, thereby maintaining blood glucose concentration for the ongoing needs of body tissues, particularly the brain. An equally important role is played by the liver in the maintenance of normal glucose tolerance in response to carbohydrate ingestion. The liver is the principal site of glucose deposition after glucose feeding, while muscle and adipose tissue represent relatively minor sites of disposal of ingested glucose. In addition, the rise in glucose and insulin caused by glucose ingestion inhibits endogenous hepatic glucose production, which serves to minimize postprandial elevations in blood glucose. When blood glucose is reduced by small increments in circulating insulin, a rebound increase in glucose output from the liver is the initial or principal mechanism counteracting the fall in blood glucose concentration. Studies in juvenile-onset diabetes indicate that the liver is capable of altering its release of glucose in response to changes in blood glucose concentration when small, physiologic doses of insulin are infused. These findings may provide an explanation for the efficacy of preprogrammed insulin delivery systems in the treatment of diabetes.
AN INEFFECTUAL ATTEMPT TO CULTIVATE THE GLOVER ORGANISM FROM CARCINOMAS
Authors: JOHN A. KOLMER
Journal: JAMA (1927)

Of the large number of organisms alleged from time to time by various investigators to be the cause of malignant new growths, that described by Glover has attracted considerable attention.  Up until a year ago, the method employed was not known; but following its publication by Glover, 1 we believed it advisable to repeat the work with scrupulous attention to every technical detail.    Our plan also included animal inoculation tests had we succeeded in securing the organism; but cultures of thirteen different tumors, listed in the accompanying table, failed to yield the organism described by him.  Glover described this organism as a gram positive, filtrable, motile organism, and stated that he isolated it and obtained cultures of it from every type of malignant tumor investigated, including human carcinoma, mouse carcinoma (63), rat carcinoma, human sarcoma, rat sarcoma (Jensen) and Rous fowl sarcoma (number 1). It is also stated that the blood
Asymptomatic carriage of Pneumocystis jiroveci in subjects undergoing bronchoscopy: a prospective study
Authors: N A Maskell
Journal: Thorax (2003)

The opportunistic fungus Pneumocystis jiroveci is a common cause of respiratory infection in immunocompromised patients. By contrast, pneumocystis pneumonia (PCP) occurs only rarely in immunocompetent individuals. Asymptomatic colonisation with P jiroveci has recently been described in patients who are either minimally immunosuppressed or who have underlying lung disorders such as bronchiectasis. We sought to determine the prevalence of asymptomatic colonisation by P jiroveci in a cohort of adult patients undergoing diagnostic bronchoscopy.A prospective observational cohort study was performed in patients who required bronchoscopy and bronchoalveolar lavage (BAL) as part of their routine clinical assessment. All the samples underwent standard microbiological analysis and a Grocott methenamine silver stain was performed where clinically indicated to detect the presence of P jiroveci. Polymerase chain reaction for detection of P jiroveci specific DNA was also performed.Ninety three consecutive BAL fluid samples were analysed, 17 (18%) of which contained P jiroveci DNA. Of the potential predictors examined, only glucocorticoid use was significantly associated with detectable P jiroveci DNA. Eighteen patients were receiving oral glucocorticoids (equivalent to >20 mg/day prednisolone) at the time of bronchoscopy, of whom eight (44%) had detectable P jiroveci DNA. In contrast, P jiroveci was detected in only nine of 75 patients (12%) who were not receiving glucocorticoids (difference between proportions 32%, 95% CI 8 to 57; p=0.004, two tailed Fisher's exact test).P jiroveci colonisation, as determined by detection of P jiroveci DNA in BAL fluid, is common in HIV negative patients with primary respiratory disorders undergoing bronchoscopy and BAL. The higher prevalence in patients receiving corticosteroids suggests that oral glucocorticoid therapy is an independent risk factor for colonisation. In contrast, underlying lung cancer or COPD did not appear to be risk factors.
Predictors of Microvascular Obstruction Assessed by the Index of Microcirculatory Resistance Following Primary Percutaneous Coronary Intervention for Acute ST-Elevation Myocardial Infarction
Authors: Ayhan Erkol, Selçuk Pala, Vecih Oduncu, Burak Turan, Can Yücel Karabay, Taylan Akgün, Kürşat Tigen, Cihan Dündar, Akın İzgi, Cevat Kırma
Journal: Journal of the American College of Cardiology (2013)