tbuckley/cabot-search huggingface dataset:
104. Role of the HI Loop in the Adeno- Associated Virus (AAV) Life Cycle
Authors: Nina DiPrimio, Aravind Asokan, Richard J. Samulski
Journal: Molecular Therapy (2006)

The fivefold axis of symmetry associated with pore region in icosahedral AAV capsids has been extensively studied in regard to its role in deploying the phospholipase A2 domain and packaging of the 4.7kb AAV genome. However, the role of the HI loops surrounding the fivefold pore, which appear to vary significantly in amino acid sequence between AAV serotypes has not been defined thus far. The HI loop is a surface-displayed peptide motif of 10-15 amino acid residues connecting the H and I beta-strands of the VP3 subunit of AAV and extends to interact with a fivefold-related neighboring subunit. In order to understand the role of this capsid region on the AAV life cycle, we substituted the HI loop in the VP3 subunit of the AAV2 capsid with corresponding regions from the VP3 subunits of AAV1, AAV4, AAV5 or AAV8. In addition, we created a deletion mutant lacking the HI loop and an AAV2 mutant substituted with a loop containing ten glycine residues. Determination of the mutant virus titers by dot blot analysis revealed that vector genome titers of AAV2HI1 (AAV1 HI loop substituted in AAV2) and AAV2HI8 displayed a two-fold decrease in titer, while AAV2HI4 displayed a ten-fold decrease in titer when compared to parental AAV2. On the other end of this spectrum, AAV2HI5, AAV2HIdel (deletion mutant), and AAV2HIpolyG (poly-glycine loop) were unable to package vector genomes. Further western and dot blot western analysis revealed that AAV2HI5 and AAV2HIdel mutants were able to synthesize capsid subunits, but unable to assemble into capsids. Interestingly, the AAV2HIpolyG mutant assembled into empty capsids highlighting the plasticity of this loop region. Further characterization of AAV HI loop mutants using transduction assays, heparin binding assays and electron microscopy are currently in progress. Our studies implicate a potential role for the HI loop in AAV genome packaging and capsid assembly.
Expression and Function of a Biological Pacemaker in Canine Heart
Authors: Jihong Qu, Alexei N. Plotnikov, Peter Danilo, Iryna Shlapakova, Ira S. Cohen, Richard B. Robinson, Michael R. Rosen
Journal: Circulation (2003)

Background— We hypothesized that localized overexpression of the hyperpolarization-activated, cyclic nucleotide-gated (HCN2) pacemaker current isoform in canine left atrium (LA) would constitute a novel biological pacemaker. Methods and Results— Adenoviral constructs of mouse HCN2 and green fluorescent protein (GFP) or GFP alone were injected into LA, terminal studies performed 3 to 4 days later, hearts removed, and myocytes examined for native and expressed pacemaker current ( I f ). Spontaneous LA rhythms occurred after vagal stimulation-induced sinus arrest in 4 of 4 HCN2+GFP dogs and 0 of 3 GFP dogs ( P &lt;0.05). Native I f in nonexpressed atrial myocytes was 7±4 pA at −130 mV (n=5), whereas HCN2+GFP LA had expressed pacemaker current ( I HCN2 ) of 3823±713 pA at −125 mV (n=10) and 768±365 pA at −85 mV. Conclusions— HCN2 overexpression provides an I f -based pacemaker sufficient to drive the heart when injected into a localized region of atrium, offering a promising gene therapy for pacemaker disease.
RNA Cargoes Associating with FMRP Reveal Deficits in Cellular Functioning in Fmr1 Null Mice
Authors: Kevin Y. Miyashiro, Andrea Beckel-Mitchener, T.Patrick Purk, Kevin G. Becker, Tanya Barret, Lei Liu, Salvatore Carbonetto, Ivan Jeanne Weiler, William T. Greenough, James Eberwine
Journal: Neuron (2003)
Vascular surgery in smokers Smokers must be allowed to decide
Authors: J Dawson, J Hotchkiss
Journal: BMJ (1994)

able extent of the lesions; the fact that "double covered" skin of the buttock was affected; the lack of lesions on habitually exposed sites; the association with profound tanning and lentiginosis in the same distribution; and the spontaneous resolution of some lesions when the patient stopped using the sunbed.Recent reports of sunbed-induced poro- keratosis34 (a histologically identifiable disorder of keratinisation, which is occasionally associated with squamous cell carcinoma) support the argu- ment that ultraviolet A sunbeds can cause discrete keratinising skin lesions.The current concerns in this patient are itch and cosmetic, but the small risk of malignant change in actinic keratoses may be important in relatively young patients with hundreds of lesions.Interestingly, appreciable itch is a feature of the hyperkeratosis that precedes the development of tumours in mice exposed to ultraviolet A.'
Effects of various anticoagulant treatments on von Willebrand factor release in unstable angina
Authors: Gilles Montalescot, Jean Philippe Collet, Linda Lison, Rémi Choussat, Annick Ankri, Eric Vicaut, Katy Perlemuter, François Philippe, Gérard Drobinski, Daniel Thomas
Journal: Journal of the American College of Cardiology (2000)
Receptor activator of nuclear factor-κB ligand (RANKL) protects against hepatic ischemia/reperfusion injury in mice
Authors: Nozomu Sakai, Heather L. Van Sweringen, Rebecca Schuster, John Blanchard, Justin M. Burns, Amit D. Tevar, Michael J. Edwards, Alex B. Lentsch
Journal: Hepatology (2011)

The transcription factor nuclear factor kappaB (NF-κB) plays diverse roles in the acute injury response to hepatic ischemia/reperfusion (I/R). Activation of NF-κB in Kupffer cells promotes inflammation through cytokine expression, whereas activation in hepatocytes may be cell protective. The interaction of receptor activator of NF-κB (RANK) and its ligand (RANKL) promotes NF-κB activation; however, this ligand-receptor system has not been studied in acute liver injury. In the current study, we sought to determine if RANK and RANKL were important in the hepatic response to I/R. Mice were subjected to partial hepatic ischemia followed by reperfusion. In some experiments, mice received recombinant RANKL or neutralizing antibodies to RANKL 1 hour prior to surgery or at reperfusion to assess the role of RANK/RANKL signaling during I/R injury. RANK was constitutively expressed in the liver and was not altered by I/R. RANK was strongly expressed in hepatocytes and very weakly expressed in Kupffer cells. Serum RANKL concentrations increased after I/R and peaked 4 hours after reperfusion. Serum levels of osteoprotegerin (OPG), a decoy receptor for RANKL, steadily increased over the 8-hour period of reperfusion. Treatment with RANKL, before ischemia or at reperfusion, increased hepatocyte NF-κB activation and significantly reduced liver injury. These beneficial effects occurred without any effect on cytokine expression or liver inflammation. Treatment with anti-RANKL antibodies had no effect on liver I/R injury. Conclusion : During the course of injury, endogenous OPG appears to suppress the effects of RANKL. However, exogenous administration of RANKL, given either prophylactically or postinjury, reduces liver injury in a manner associated with increased hepatocyte NF-κB activation. The data suggest that RANK/RANKL may be a viable therapeutic target in acute liver injury.
A Controlled Trial of Bismuth Subsalicylate in Infants with Acute Watery Diarrheal Disease
Authors: Dante Figueroa-Quintanilla, Eduardo Salazar-Lindo, R. Bradley Sack, Raul Leon-Barua, Silvana Sarabia-Arce, Miguel Campos-Sanchez, Eduardo Eyzaguirre-Maccan
Journal: New England Journal of Medicine (1993)

Bismuth subsalicylate is a common constituent of over-the-counter medications for diarrhea. However, it is uncertain whether bismuth offers any more benefit than standard oral rehydration therapy with early feeding.We conducted a placebo-controlled, randomized trial to evaluate the effect of bismuth subsalicylate (100 or 150 mg per kilogram of body weight per day for up to 5 days) on the duration and volume of acute watery diarrhea in 275 male infants and young boys (mean age, 13.5 months). Serum salicylate and bismuth levels were monitored throughout the study and were also measured two weeks after discharge. All the patients received fluid replacement by the oral route and early feeding of easily digestible foods with high caloric density.Diarrhea stopped within 120 hours of admission in 74 percent of the patients given placebo, 89 percent of those given 100 mg of bismuth per kilogram (P = 0.009 vs. the placebo group), and 88 percent of those given 150 mg of bismuth per kilogram (P = 0.019 vs. the placebo group). As compared with the patients given placebo, those given bismuth had significant reductions in their total stool output (P = 0.015), total intake of oral rehydration solution (P = 0.013), and duration of hospitalization (P = 0.005); there was no significant difference between the two groups given bismuth in these clinical outcomes. All measurements of bismuth and salicylate concentrations in blood were well below concentrations considered toxic. No adverse reactions were seen.Treatment with bismuth subsalicylate decreases the duration of diarrhea and is a safe and effective adjunct to oral rehydration therapy for infants and young children with acute watery diarrhea.
2014 Hypertension Recommendations From the Eighth Joint National Committee Panel Members Raise Concerns for Elderly Black and Female Populations
Authors: Lawrence R. Krakoff, Robert L. Gillespie, Keith C. Ferdinand, Icilma V. Fergus, Ola Akinboboye, Kim A. Williams, Mary Norine Walsh, C. Noel Bairey Merz, Carl J. Pepine
Journal: Journal of the American College of Cardiology (2014)
Managing change: the human aspects of the NHS.
Authors: E Lauermann
Journal: BMJ (1993)

Whatever ministers actually decide about London following the Tomlinson report, the changes are likely to be large-scale and affect many staff and patients. Therefore how well those changes are handled becomes crucial to their success. The NHS has much to learn from other industries and organisations that have been through similar changes. Firstly, there needs to be an overall strategy for the change, rather than individual units trying to manage their own parts of it in an ad hoc way. Secondly, how well those made redundant are treated is an important factor in maintaining the morale of those who stay behind. For those affected by changes the NHS needs to provide full information, imagination, time, emotional and practical support, and money. Though decisions need to be made quickly, their implementation should take as much time as is necessary.
Pregnancy Outcome and Maternal Infection: The Need for Comprehensive Studies
Authors: Michael G. Gravett
Journal: JAMA (1983)

The perinatal mortality rate has declined dramatically in the United States during the last three decades. Prematurity accounts for 70% to 80% of all perinatal deaths that are not caused by severe congenital malformations,<sup>1</sup>yet the rate of prematurity has not declined in the last 30 years. Thus, the decline in perinatal mortality is attributable to improved neonatal care, which has been achieved only at great cost. The estimated cost of term and premature neonatal care in the United States in 1980 was $460 million. If all neonates treated in neonatal intensive care units had instead been delivered as healthy term babies, the estimated cost for all neonatal care would have been only $50 million.<sup>2</sup>The additional cost of subsequent neurological morbidity in premature newborns who survive is difficult to assess. Further reduction of the perinatal death rate and the cost of neonatal care and of subsequent morbidity
Should Patients With Diabetes Drink to Their Health?
Authors: Michael H. Criqui
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
INTERNISTS AND PSYCHIATRY
Authors: RUSSELL M. WILDER
Journal: Annals of Internal Medicine (1969)

Letters and Comments1 July 1969INTERNISTS AND PSYCHIATRYRUSSELL M. WILDER, M.D.RUSSELL M. WILDER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-71-1-213 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: I have been somewhat depressed by the implications in the editorial, "Stale, Soft, or Chronic" (Ann. Intern. Med. 70: 1272, 1969). Let me share a few thoughts with ANNALS readers, derived from my own experience.Firstly, I think the emphasis on subspecialty training seen throughout medicine and the emphasis on research has meant that the identification model preferred by most students and medical residents has tended to be the laboratory-oriented teacher, often himself unaware of the bread and butter problems of everyday medical practice because so much of his professional life has been spent in academic settings.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Menninger Foundation Topeka, Kan. 66601 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1969Volume 71, Issue 1Page: 213-214KeywordsAcademic medicineBreadSub-specialty care Issue Published: 1 July 1969 PDF downloadLoading ...
Abstract 10778: Relation Between Time to Arousal and Neurologic Outcomes in Cardiac Arrest Patients Treated with Therapeutic Hypothermia
Authors: Anne V Grossestreuer, Marion Leary, Benjamin S Abella, David F Gaieski
Journal: Circulation (2011)

Background: The use of therapeutic hypothermia (TH) improves outcomes after resuscitation from cardiac arrest. However, patients often remain comatose for days following resuscitation and therefore...
475 DIFFERENCES IN THE ROLE OF QUANTITATIVE HEPATITIS B SURFACE ANTIGEN BETWEEN HBEAG SEROPOSITIVE AND SERONEGATIVE INDIVIDUALS WITH CHRONIC HEPATITIS B
Authors: J. Liu, M.-H. Lee, R. Batrla-Utermann, C.-L. Jen, U.H. Iloeje, S.-N. Lu, L.-Y. Wang, S.-L. You, K.C. Hsiao, H.-I. Yang, C.-J. Chen
Journal: Journal of Hepatology (2012)
Acquired hypoprothrombinemia: Effects of Danazol® treatment
Authors: Sybil Williams, Corinne Linardic, Olga Wilson, Philip Comp, Harvey R. Gralnick
Journal: American Journal of Hematology (1996)

The lupus anticoagulant may be accompanied by an acquired factor II deficiency and bleeding. We report on a patient with a lupus anticoagulant and factor II (FII) deficiency responsive to Danazol®. Acquired hypoprothrombinemia (FII) with the lupus anticoagulant (LA) may be accompanied by a hemorrhagic diathesis. A 64-year-old male with discoid lupus erythematosis bled after an intestinal polypectomy. His FII level was 18%, and his FII antigen level was 20%. Danazol® (D) (600 mg per day) administration was associated with a rise in FII activity and antigen to 50% within 10 days. The patient underwent abdominal surgery. We studied the effect(s) of D on the FII level and on other coagulation factors in this patient. The patient's plasma FII antigen had a single precipitin arc compared to the two peaks of normal plasma on counterimmunoelectrophoresis with Ca++. The samples pre- and during D therapy had the same positively charged arc as normal samples, although they were quantitatively different. Neuraminidase treatment demonstrated a decrease in the positively charged migration of normal and the patient's FII antigen. Affinity chromatography of normal and patient plasma on a Sepharose protein A column revealed FII antigen present in the patient's bound fraction. The relative percentages of bound FII before and during D treatment were similar. During D therapy, levels of FIX and X rose 50-100%, and protein C rose 20-25%, while free protein S did not change. D is an effective therapy for acquired FII deficiency associated with LA. D does not affect the binding of Ig to FII, but D raises FII levels by increasing synthesis of the FII protein. (This article is a US Government work and, as such, is in the public domain in the United States of America.) © 1996 Wiley-Liss, Inc.
Community based approaches to the control of multidrug resistant tuberculosis: introducing "DOTS-plus"
Authors: P. Farmer, J. Y. Kim
Journal: BMJ (1998)

Tuberculosis remains the world's leading infectious cause of adult deaths, most of which are due not to multidrug resistant tuberculosis but to lack of access to effective treatment for drug susceptible tuberculous disease.1 New data suggest, however, that multidrug resistant tuberculosis is emerging as an increasingly important cause of morbidity and death. In the United States, Europe, and Latin America, highly resistant strains of tuberculosis have caused explosive institutional outbreaks (in hospitals, prisons, and homeless shelters) with high case fatality rates among immunosuppressed people and high rates of transmission to other patients and to caregivers and their families.2–8

These outbreaks are not restricted to certain regions. The WHO/International Union Against Tuberculosis and Lung Disease's global survey of resistance to antituberculous drugs now reveals that multidrug resistant tuberculosis has already become established worldwide. In several countries—including Russia, Estonia, Latvia, Cote d'Ivoire, and the Dominican Republic—“hot zones” of ongoing transmission have been identified. Failure to follow the World Health Organisation's guidelines was clearly associated with high rates of multidrug resistant tuberculosis; the survey was thus able to identify countries in which an increase in multidrug resistant tuberculosis was likely, given the current programme conditions.9

#### Summary points

Multidrug resistant tuberculosis is already a global pandemic, with focal “hot zones” of increased transmission

Although DOTS (directly observed treatment, short course) chemotherapy is the goal of global tuberculosis control, short course chemotherapy will not cure multidrug resistant tuberculosis

In settings of high transmission of multidrug resistant tuberculosis, “DOTS-plus” (a complementary DOTS based strategy with provisions for treating multidrug resistant tuberculosis) is warranted

Community based strategies designed to enhance local capacity are cost effective and make it possible to meet new medical challenges

Unfortunately, treatment options have been limited for most people with multidrug resistant tuberculosis, largely because of the cost of drugs. …
Effect of angiotensin II type 1 receptor blockade on experimental hepatic fibrogenesis
Authors: Georgina Paizis, Richard E Gilbert, Mark E Cooper, Padma Murthi, Josefa M Schembri, Leonard L Wu, Jonathan R Rumble, Darren J Kelly, Christos Tikellis, Alison Cox, Richard A Smallwood, Peter W Angus
Journal: Journal of Hepatology (2001)
Age-related normalization of the browning rate of collagen in diabetic subjects without retinopathy.
Authors: V M Monnier, C A Elmets, K E Frank, V Vishwanath, T Yamashita
Journal: Journal of Clinical Investigation (1986)

The age-related changes in collagen-linked fluorescence (browning) were investigated in skin from subjects with long-standing type I diabetes. Overall browning rates were 2.4 times higher in diabetics than in controls (P less than 0.02) and slope intercept accurately reflected the mean age of onset of diabetes (11.6 vs. 11.2 yr), suggesting that the browning process has the attributes of a biological clock. Browning rates were not different in controls and diabetics without retinopathy (P greater than 0.05) but were 2.4 (P less than 0.05) and 2.7 (P less than 0.01) times increased in the presence of background and proliferative retinopathy, respectively. Compared with subjects with retinopathy, individual browning rates since onset of diabetes decreased with advancing age in subjects free of retinopathy (P less than 0.001). Extrapolation revealed that they would become identical to that of nondiabetic subjects by the age of 66.4 yr. These results suggest the presence of a mechanism that controls the browning rate of collagen in diabetics who do not develop retinopathy.
Dysphagia and a skin rash
Authors: G. Watermeyer, D. Epstein, S. Hlatshwayo, D. George, M. Locketz, H. Omar, R. Spiller
Journal: Gut (2008)

A 44-year-old-woman, previously well with no medical history of note, presented with acute onset dysphagia and odynophagia. She denied any other gastrointestinal symptoms. On examination a vesiculopustular rash of the upper extremities (fig 1) was noted, as well …
The Measurement of Human Skill: Part II
Authors: F. C. Bartlett
Journal: BMJ (1947)

operative in such occupations as that of furnacemen, if face and hands should be shown to be frequently involved in these workers.Classification according to site in official returns is needed to increase the value of correlations with occupational or other social factors.Correlations with geography, or hours of sun- light in different parts of the British Isles and elsewhere, should also have value.We are grateful to Prof. E. L. Kennaway for criticisms and small corrections embodied in the text.
Sickle hemoglobinopathies in sicily
Authors: G. Schilirò, M. Spena, E. Giambelluca, A. Maggio
Journal: American Journal of Hematology (1990)

Abstract The clinical and hematological features of 202 Sicilian subjects with sickle cell disease are reported, 41 being homozygous for beta S (β S β S ), 64 with beta s thal beta S (β s β S ), and 97 beta + thal beta S (β + β S ). Analysis of the findings showed that the disease observed in Sicilians is of intermediate severity and falls between the severe form observed in patients of African origin and the milder one seen in subjects of Arabian origin.
Swimming pool attendance and risk of asthma and allergic symptoms in children
Authors: L. Font-Ribera, M. Kogevinas, J-P. Zock, M. J. Nieuwenhuijsen, D. Heederik, C. M. Villanueva
Journal: European Respiratory Journal (2009)

Increased asthma risk has been associated with pool attendance in children but evidence is inconsistent and inconclusive. A survey was conducted of 3,223 9–12-yr-old children in Sabadell (Spain) to evaluate association between swimming pool attendance and prevalence of asthma and allergic conditions and symptoms. Parents completed a questionnaire on lifetime frequency of pool attendance and symptoms in the last 12 months (wheezing, asthma medication, rhinitis and allergic rhinitis), ever having asthma and eczema, and potential confounders. Indicators of indoor and outdoor swimming pool attendance early in life, cumulatively and currently were calculated. Swimming pool attendance before the age of 2 yrs was associated with slightly lower prevalence of current asthma (OR 0.79, 95% CI 0.43–1.46), rhinitis (OR 0.86, 95% CI 0.68–1.08) and allergic rhinitis symptoms (OR 0.72, 95% CI 0.54–0.96) compared to those who started attending swimming pools after 4 yrs of age. An increased prevalence of eczema was associated with duration of lifetime pool attendance (OR 1.71, 95%CI 1.38–2.12 for &gt;5 yrs <i>versus</i> 0 yrs). Swimming pool attendance in Spanish children was associated with slightly less upper and lower respiratory tract symptoms and with more eczema. Longitudinal studies are required to confirm these findings and avoid potential reverse causation.