tbuckley/cabot-search huggingface dataset:
CD26/dipeptidyl-peptidase IV in psoriatic skin: upregulation and topographical changes
Authors: R.G. van Lingen, P.C.M. van de Kerkhof, M.M.B. Seyger, E.M.G.J. de Jong, D.W.A. van Rens, M.K.P. Poll, P.L.J.M. Zeeuwen, P.E.J. van Erp
Journal: British Journal of Dermatology (2008)

Psoriasis is known to affect 2-3% of the population and can be considered an organ-specific autoimmune disease. CD26/dipeptidyl-peptidase IV (DPP-IV) is a membrane-bound protease with diverse properties. In theory, the expression of CD26/DPP-IV has common grounds with three principal key players of the psoriatic pathogenesis: keratinocytes, T cells and cytokines.To assess CD26/DPP-IV expression in psoriasis in order to expand on the search for complementary biomarkers related to inflammation and proliferation in psoriasis.The pattern of expression of CD26/DPP-IV was investigated on the mRNA-, protein- and enzyme-functionality level using immunohistochemical, immunofluorescent and enzyme activity labelling techniques.An 11-fold significant increase of CD26/DPP-IV on the mRNA level was demonstrated in psoriatic epidermal sheets compared with normal skin. Immunohistochemistry on psoriatic sections showed a distinct patchy honeycomb-like CD26/DPP-IV staining in the suprapapillary layers. Moreover, a clearly distinguishable column-like staining pattern throughout the suprabasal compartment along the rete ridges was seen, whereas in normal skin these patterns were absent. Strikingly, CD26/DPP-IV enzyme activity correlated with this immunohistochemical reactivity pattern for the CD26/DPP-IV protein. The T-cell bound expression of CD26/DPP-IV in psoriatic skin was explicitly present, albeit in small quantities.Our data provide clear evidence for a versatile upregulation of CD26/DPP-IV expression in psoriatic (epi)dermis. Although the exact functional contribution remains speculative, the topographical distribution of this complex multifunctional protein suggests a suitable role as a complementary biomarker in psoriasis.
The Physiologic Importance of Pulsatile Blood Flow
Authors: H. Wilkens, W. Regelson, F. S. Hoffmeister
Journal: New England Journal of Medicine (1962)

NOT since the time of Hippocrates has the diagnostic value of the arterial pulse been disputed. Yet its role in physiology is considered of little, if any, consequence. Typical of this attitude was Wesolowski's1 statement that "the presence of the pulse may represent nothing more in physiological terms than an expression of the limitations of the organic heart design." Indeed, this concept is reflected by clinicians using "nonpulsatile"† delivery of blood during partial and total body perfusion. We should like to propose that a review of the physiologic disturbances encountered in "nonpulsatile" perfusion and a consideration of the progressive phylogenetic . . .
Back to the Land or The Little Dumb Hen
Authors: Walden S. Morton
Journal: Annals of Internal Medicine (1997)

Ad Libitum1 June 1997Back to the Land or The Little Dumb HenWalden S. MortonWalden S. MortonCape Elizabeth, ME 04107Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-11-199706010-00007 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail “Do I HAVE to go pick them?” “It's ITCHY in the corn ... Author, Article, and Disclosure InformationAffiliations: Cape Elizabeth, ME 04107Corresponding Author: Walden S. Morton, 387 Mitchell Road, Cape Elizabeth, ME 04107. Previousarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1997Volume 126, Issue 11Page: 891KeywordsBeesBreadFoodSwimming ePublished: 15 August 2000 Issue Published: 1 June 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
13. Persistence of AAV Capsid in Transduced Cells
Authors: Mo-Ying Hsieh, Fayaz R. Khazi, Alexander Schlachterman, Yi-Lin Liu, Katherine A. High
Journal: Molecular Therapy (2005)

Adeno-associated virus (AAV) vector mediated liver-directed gene transfer has been used to effect long-term cure of hemophilia B in the canine model. Based on these data, a clinical trial was performed on subjects with severe hemophilia B. Vector was introduced through the hepatic artery and at the highest dose tested (2 |[times]| 1012 vg/kg) resulted in therapeutic levels of F.IX (|[sim]|10%) that persisted at this level for 4 weeks and then declined over the ensuing six weeks to baseline levels (<1%). As F.IX levels fell, liver transaminases rose and then returned to normal. Detailed study of a subsequent patient infused with AAV-F.IX documented a transient T cell response to AAV capsid but not to F.IX on IFN-|[gamma]| ELISPOT. We hypothesized that the transduced cells were destroyed by an immune response to AAV capsid and that since this antigen is not long-lived, transient immunosuppression may allow persistence of expression. We therefore initiated studies to determine the duration of AAV-2 capsid persistence in transduced cells. The AAV capsid is composed of three proteins, VP1, 2, and 3. The B1 antibody has been shown to recognize all three capsid proteins in the nonassembled form. We transduced HeLa cells with AAV2 vectors at a MOI of 100,000 at 37 |[deg]|C for 2 hrs. In the nuclear extract, capsid proteins could be detected by B1 antibody on Western blot after 0, 6, 16, and 24 hrs post transduction. Capsid proteins were no longer detectable after 48 hrs post transduction. In the cytoplasmic extract, no signal was detected by Western blot with B1 antibody at any time point except time 0 after transduction. The result indicates that vectors enter the nucleus or are tightly bound to the nuclear envelope at an early stage. A similar phenomenon was also observed using immunocytochemistry staining with the B1 antibody. In the nucleus, capsid proteins could be detected up to 16 hrs and disappeared to undetectable levels after 24 hrs post transduction.
The Contribution of LTR Retrotransposon Sequences to Gene Evolution in Mus musculus
Authors: Jeremy D. DeBarry, Eric W. Ganko, Eugene M. McCarthy, John F. McDonald
Journal: Molecular Biology and Evolution (2005)

Approximately 1.5% of mouse genes (Mus musculus) contain long terminal repeat retrotransposon sequences (LRS). Consistent with earlier findings in Caenorhabditis elegans, Drosophila melanogaster, and Homo sapiens, LRS are more likely to be associated with newly evolved genes. Evidence is presented that LRS are often recruited as novel exons or as spliced additions to existing exons. These novel gene configurations may be expressed initially as alternative transcripts providing an opportunity for the evolution of new gene function.
Lack of efficacy of 9-aminocamptothecin in adults with newly diagnosed glioblastoma multiforme and recurrent high-grade astrocytoma
Authors: Fred Hochberg, Stuart A. Grossman, Tom Mikkelsen, Michael Glantz, Joy D. Fisher, Steven Piantadosi
Journal: Neuro-Oncology (2000)

9-Aminocamptothecin (9-AC) was administered as a 72-h i.v. infusion every 2 weeks to a total of 99 adults with high-grade astrocytomas. Fifty-one patients with newly diagnosed glioblastoma multiforme received 9-AC treatment prior to radiation therapy and 48 patients with high-grade astrocytomas were treated at the time of tumor recurrence. Upon entrance into these research protocols, all patients had measurable disease that was evaluated on a monthly basis with volumetric CT or MRI scans. A partial response was defined by > or =50% reduction in the contrast enhancing volume on stable or decreasing doses of glucocorticoids. The study specified that all apparent responders would have central review of their radiologic studies and histopathology. The initial patients treated with 9-AC were also receiving anticonvulsants and were noted to have minimal myelosuppression with this chemotherapy. Thus, 9-AC doses were escalated from the previously reported maximum tolerated dose (MTD) of 850 microg/m2/24 h. We then established new MTDs for patients receiving enzyme-inducing anticonvulsants. We defined these MTDs to be 1,776 microg/m2/24 h for newly diagnosed, previously untreated patients and 1,611 microg/m2/24 h for patients with recurrent disease. Twenty-two patients with newly diagnosed glioblastoma multiforme received 9-AC at doses > or =1,776 microg/m2/24 h. Of these, 18 had evaluable disease on central review, and 0 of 18 (0%) demonstrated a partial or complete response. Twenty-one patients with recurrent high-grade astrocytomas were treated at 1,611 microg/m2/24 h; 20 had evaluable disease and 0 of 20 (0%) had a partial or complete response. Thus, the overall response rate in the 38 evaluable patients treated at the MTD was 0 of 38 (0%). Furthermore, of the 51 evaluable patients who were treated at doses less than the MTD, only one partial response was observed, yielding an overall response rate of 2%. Evidence of drug failure was rapid with tumor progression in one-half of patients after 2 drug cycles. 9-AC lacks evidence of substantial activity in patients with newly diagnosed or recurrent high-grade astrocytomas.
Testing Topical Antibacterial Drugs
Authors: RICHARD R. MARPLES
Journal: Annals of Internal Medicine (1971)

Editorial Notes1 June 1971Testing Topical Antibacterial DrugsRICHARD R. MARPLES, B.M., M.SC.RICHARD R. MARPLES, B.M., M.SC.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-6-1009_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptClinical testing of topical drugs in skin infections looks simple but is in fact very difficult to carry out and interpret. Two recent reports from Australia (1, 2) on phenanthroline metal chelates demonstrate typical hazards in such trials. The first study, of manganese chelates, is described as a controlled clinical trial but is in fact a comparison between these compounds and either an antibiotic-dequalinium combination (Neodequin) or a chlorinated benzoic acid derivative (Jadit). A placebo group was not included. In the comparison groups, paired lesions were treated simultaneously, a practice notoriously unreliable. Not only are patients likely to apply accidentally...References1. CADESHANKLYSHULMAN GKA: The treatment of dermatological infections with a manganese phenanthroline chelate. Med J Aust 2:304-309, 1970 CrossrefMedlineGoogle Scholar2. BUTLERLAVERSHULMAN HJA: The use of phenanthroline metal chelates for the control of topical infections due to bacteria fungi and protozoa. Ibid., pp. 309-314 Google Scholar3. BURNETT J: Management of pyogenic cutaneous infections. New Eng J Med 266:164-169, 1962 CrossrefMedlineGoogle Scholar4. DILLON H: Pyoderma and nephritis. Ann Rev Med 18: 207-218, 1967 CrossrefMedlineGoogle Scholar5. MAIBACHKLIGMAN HA: The biology of experimental human cutaneous moniliasis (Candida albicans). Arch Derm (Chicago) 85:233-257, 1962 CrossrefMedlineGoogle Scholar6. MARPLESKLIGMAN RA: In vivo methods for appraising antibacterial agents. Toilet Goods Ass Cosmetics J 1:26-33, 1969 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Dermatology School of Medicine University of Pennsylvania Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1971Volume 74, Issue 6Page: 1009-1010KeywordsClinical trialsDrugsLesionsSkin infections Issue Published: 1 June 1971 PDF downloadLoading ...
Gene therapy for inherited blindness shows promise in first clinical trial
Authors: I. Torjesen
Journal: BMJ (2014)

The first phase I clinical trial of gene therapy for an inherited cause of blindness has shown sustained improvements in visual acuity. 

In the trial, funded by the Department of Health for England and the Wellcome Trust, six patients had genes injected into the retinal cells of one eye, with no adverse effects. Six months later all the patients reported improvements in their vision in dim light, and two of the six, who have now been followed up for up to two years, were able to read more lines on an eye chart.

The six patients who received the gene therapy had choroideraemia, a rare inherited blindness that affects one in 50 000 people and for which there is no treatment.

A third of eye disorders have a …
The VPS33B-binding protein VPS16B is required in megakaryocyte and platelet α-granule biogenesis
Authors: Denisa Urban, Ling Li, Hilary Christensen, Fred G. Pluthero, Shao Zun Chen, Michael Puhacz, Parvesh M. Garg, Kiran K. Lanka, James J. Cummings, Helmut Kramer, James D. Wasmuth, John Parkinson, Walter H. A. Kahr
Journal: Blood (2012)
Asthma and breast feeding
Authors: D OBERLE
Journal: Thorax (2001)

Wright et al 1 found an increased risk for asthma and wheeze in breastfed children whose mothers had asthma themselves. Data on 9644 children aged 5–6 years from the Bavarian farmers' study2 allowed us to test whether this somewhat unexpected finding is reproducible in a different setting.

Lifetime prevalence of doctor diagnosed asthma (physicians' …
General practitioners prefer to work in cooperatives for out of hours work
Authors: P. Hughes, R. D Neal, N. Maskrey
Journal: BMJ (1997)

Rationing health careAllocating resources only to treating present dangers would ruin preventive health care and jeopardise future livesEditor-In his article on the objectives of the NHS John Harris argues that "there is a good principle that real and present dangers should be met before future and speculative ones." 1 Has he really thought about the implications of this?Immunisation, health promotion, and preventive interventions would all be swept away in favour of curative treatments.As the lives lost by such a shift in resources would be future lives and the people not identifiable beforehand, they would count for nothing.The state's obligation to protect the "citizen against threats to her life and liberty" only applies to immediate threats.Harris argues that the health budget should be larger, as if a larger budget will somehow allocate itself and obviate the need for choosing between competing alternatives.He also claims that health care (and he means curative care) should be afforded a high priority in the state budget.This presents a simple dilemma: should the state spend more on raising the income of impoverished families or on resources to provide more intensive care beds?Since raising the income of poor families has no impact on immediate threats to health, according to Harris we must clearly prefer spending more on providing more intensive care beds.Harris fails to recognise the first problem in identifying healthcare needs.If resources are not the immediate constraint on a healthcare system then rationing takes place on the basis of whether a need (or a want) can be legitimised as a healthcare need.In times of plenty the remit of formal health care expands.Harris seems to desire this process to continue.In wishing for more of our labour to be devoted to financing this end, he can see no cost or opportunity cost to the process.Am I alone in finding this naive?
Delayed Preconditioning-Mimetic Actions of Nitroglycerin in Patients Undergoing Exercise Tolerance Tests
Authors: Hani Jneid, Mukul Chandra, Motaz Alshaher, Carlton A. Hornung, Xian-Liang Tang, Massoud Leesar, Roberto Bolli
Journal: Circulation (2005)

Background— Nitroglycerin (NTG) induces delayed preconditioning (PC)-mimetic effects in animal models and in humans during coronary angioplasty. We tested the hypothesis that NTG mitigates ischemia and enhances functional capacity during an exercise tolerance test (ETT) in patients with coronary artery disease. Methods and Results— Twenty-eight patients with stable angina and ischemia documented by a stress test were randomized in a double-masked, crossover design to receive a titrated intravenous infusion of NTG or normal saline over 4 hours. At 24 to 28 hours after study medication infusion, each patient underwent 2 ETTs separated by a 1-week washout period. Compared with control patients, pretreatment with NTG was associated with a dose-dependent increase in exercise duration averaging 40 seconds (412±19 versus 372±24 seconds, P =0.014) and an improvement in ECG manifestations of ischemia, as shown by a decrease in maximal ST-segment depression (1.84±0.14 versus 1.63±0.13 mm, P =0.011), sum of ST-segment depressions in 12 leads (7.64±1.01 versus 6.61±0.83 mm, P =0.027), and time to resolution of ST-segment depression (229±30 versus 207±28 s, P =0.018). These benefits occurred despite an increase in myocardial workload after NTG, as indicated by a higher peak rate-pressure product (24 492±1054 versus 22 536±1019 mm Hg/min, P =0.015). Conclusions— NTG produces a late PC-mimetic effect that mitigates the ECG manifestations of ischemia during exercise and improves exercise capacity. To our knowledge, this is the first study to demonstrate that NTG can alleviate exercise-induced ischemia 24 hours after its administration, long after the hemodynamic effects have subsided. The finding that nitrate-induced late PC ameliorates a common manifestation of coronary artery disease has potentially significant implications for the management of this disorder and for the design of clinical trials.
Physicians and the Acquired Immunodeficiency Syndrome
Authors: Larry Gostin
Journal: JAMA (1990)

<h3>To the Editor.—</h3> I have written about,<sup>1</sup>and given careful thought to, the issues posed by Gerbert et al<sup>2</sup>on the human immunodeficiency virus (HIV)-infected physician. Should physicians be required to disclose to their patients that they are infected with HIV? The law of informed consent requires disclosure of material risks to patients. However, the risk of transmission from physician to patient is so remote that the law ought not to require disclosure. A physician could not realistically continue to practice medicine when patients in the community know of his or her infection. Should infected physicians be restricted in the practice of medicine? There are at least 14 court cases where health care professionals have been excluded from their practices by hospitals or physician partnerships.<sup>3</sup>Patients cannot be assured a risk-free hospital environment. Provided the risks are remote, and rigorous precautions are used, infected physicians should be
Contractility in Isolated Mammalian Heart Muscle after Acid-Base Changes
Authors: HORACIO E. CINGOLANI, ALICIA R. MATTIAZZI, ENRIQUE S. BLESA, NORBERTO C. GONZALEZ
Journal: Circulation Research (1970)

In-vitro experiments performed in cat papillary muscles and strips of rat right ventricle suggest that the changes in myocardial contractility that follow acid-base disturbances are not a function of extracellular pH. Simultaneous changes in Pco 2 and NaHCO 3 concentration, with extracellular pH constant, decreased developed tension and maximal rate of rise of the tension (dT/dt) without significant changes in the time to peak tension when the muscle was exposed to the solution with higher Pco 2 and NaHCO 3 concentration. At an extracellular pH of 7.40, developed tension decreased 0.51 ± 0.13 g/mm 2 ( P &lt; 0.02) and dT/dt decreased 1.29 ± 0.50 g/sec ( P &lt; 0.05) with no significant change in time to peak tension (0.038 ± 0.022 sec). Changes in pH produced by increasing Pco 2 at constant NaHCO 3 concentration were followed by a significant decrease in contractility. A change of Pco 2 from 20 to 90 mm Hg that produced a change in extracellular pH from 7.60 to 7.00 was accompanied by a decrease in developed tension of 0.67 ± 0.14 g/mm 2 ( P &lt; 0.01), in dT/dt of 2.63 ± 0.54 g/sec ( P &lt; 0.01) with no changes in time to peak tension (0.0017 ± 0.10 seconds). We were unable to show significant variations in contractility when extracellular pH was changed at a constant Pco 2 of approximately 21 mm Hg (NaHCO 3 7.5, 15, and 30 m M ) or at a Pco 2 of approximately 95 mm Hg (NaHCO 3 15, 30, 60, 80 and 120 m M ). Only when extracellular pH reached a value as high as 8.0 (Pco 2 21 mm Hg, NaHCO 3 80 m M ) a small but significant increase in contractility was evidenced. Either Pco 2 or intracellular pH could be the major determinants of the changes in myocardial contractility that follow acid-base alterations.
Prevention Conference VII
Authors: Sachiko T. St. Jeor, Laura L. Hayman, Stephen R. Daniels, Matthew W. Gillman, George Howard, Catherine M. Law, Cora Elizabeth Lewis, Eric Poehlman
Journal: Circulation (2004)

D ynamic processes that occur over the life span determine the development of obesity and associated chronic diseases.Perturbations, or "insults," that determine excessive weight gain leading to obesity may occur anytime from before conception to embryonic, fetal, infant, childhood, adolescent, and adult life.These insults can affect both somatic growth and the maturation of metabolic systems and may include a range of determinants, including societal, lifestyle, biological, and genetic factors that often act in concert with one another.A life-course approach to chronic disease (Figure 1) classifies determinants in several different ways. 1 A critical period refers to a specific period of development when an insult has lasting effects on the structure or function of organs, tissues, and body systems.When the insult is not completely deterministic, these periods may be referred to as sensitive rather than critical.Effects during critical periods may act alone or be modified by later insults.Alternatively, some insults may act at any period of development; they may accumulate over time independently or be correlated through clustering.These models are useful in helping determine which early life factors are important in the assessment of later disease.Although age-dependent risk factors may vary worldwide, identification of common critical or sensitive periods and plausible determinants will help improve overall treatment and prevention of obesity over the life span.
Percutaneous Polyethylene Tube Tracheostomy
Authors: Richard N. Myers
Journal: JAMA (1965)

Pulmonary complications consequent to surgical operations or serious illnesses continue to present a major problem in the management of patients. The variety of techniques previously employed for the prevention of these complications would indicate that no single method has been ideal. Since prevention is preferable to treatment, a single, safe, and effective method would seem desirable. Percutaneous polyethylene tube tracheostomy appears to fulfill these criteria. This method utilizes the percutaneous insertion of a small polyethylene catheter into the trachea, which in turn serves as a means for intratracheal instillation of various agents. A paroxysm of coughing is thus invoked, and the respiratory tree cleared of secretions. Using a modification of the originally described technique,<sup>1,2</sup>percutaneous tracheostomy has been done in over 200 medical and surgical patients during the past four years without complications. <h3>Technique</h3> After sterile preparation and draping of the anterior part of the neck, a skin wheal
Medical Malpractice Liability in the Age of Electronic Health Records
Authors: Sandeep S. Mangalmurti, Lindsey Murtagh, Michelle M. Mello
Journal: New England Journal of Medicine (2010)

EHRs can improve the quality of care and reduce medical-liability risks; this review includes a discussion of the malpractice-liability implications of computerized order entry, clinical-decision support, electronic messaging with patients, and the transition to EHRs.