tbuckley/cabot-search huggingface dataset:
Distinct populations of basal keratinocytes express stromelysin-1 and stromelysin-2 in chronic wounds.
Authors: U K Saarialho-Kere, A P Pentland, H Birkedal-Hansen, W C Parks, H G Welgus
Journal: Journal of Clinical Investigation (1994)

Wound repair involves cell migration and tissue remodeling, and these ordered and regulated processes are facilitated by matrix-degrading proteases. We reported that interstitial collagenase is invariantly expressed by basal keratinocytes at the migrating front of healing epidermis (Saarialho-Kere, U. K., E. S. Chang, H. G. Welgus, and W. C. Parks, 1992. J. Clin. Invest. 90:1952-1957). Because of the limited substrate specificity of collagenase, principally for interstitial fibrillar collagens, other enzymes must also be produced in the wound environment to effectively restructure tissues with a complex matrix composition. Stromelysins-1 and -2 are closely related, yet distinct metalloproteinases, and both can degrade many noncollagenous connective tissue macromolecules. Using in situ hybridization and immunohistochemistry, we found that both stromelysins are produced by distinct populations of keratinocytes in a variety of chronic ulcers. Stromelysin-1 mRNA and protein were detected in basal keratinocytes adjacent to but distal from the wound edge in what probably represents the sites of proliferating epidermis. In contrast, stromelysin-2 mRNA was seen only in basal keratinocytes at the migrating front, in the same epidermal cell population that expresses collagenase. Stromelysin-1-producing keratinocytes resided on the basement membrane, whereas stromelysin-2-producing keratinocytes were in contact with the dermal matrix. Furthermore, stromelysin-1 expression was prominent in dermal fibroblasts, whereas no signal for stromelysin-2 was seen in any dermal cell. These findings demonstrate that stromelysins-1 and -2 are produced by different populations of basal keratinocytes in response to wounding and suggest that these two matrix metalloproteinases serve distinct roles in tissue repair.
Dyspnea in Cyanotic Congenital Heart Disease Treated With Air at 70 psi
Authors: Marvin L. Auerback
Journal: JAMA (1987)

To the Editor.—  An 18-year-old man with cyanotic congenital heart disease (corrected transposition with tight pulmonic stenosis and ventricular septal defect and a Blalock-Taussig shunt) began to complain of increasing cyanosis and dyspnea after riding his bike the one mile to and from his home and school.  His symptoms suggested that he was outgrowing his shunt and preparations were begun for studies at the local medical center. Just before his admission, however, his mother canceled it, explaining that the au pair staying at her house had asked why Jason insisted on riding a bike with two flat tires. The addition of 70 psi of air to his bicycle tires ended his complaints.
New Editor of Molecular Therapy
Authors: Inder M. Verma
Journal: Molecular Therapy (2002)

Robert (Rob) Murray Frederickson has been appointed the Managing Editor of Molecular Therapy starting August 26, 2002. He will take over the responsibilities previously carried out by Fintan Steele. Rob obtained his Ph.D. in Biochemistry and Cell Biology in 1994 from McGill University in Montreal, Canada. He then joined Nature magazine as an assistant biology editor. From 1996 to 1998 Rob worked in the laboratory of Stan Fields at the University of Washington in Seattle as a postdoctoral fellow. In 1998 Rob rejoined the Nature group, first as Research Editor for Nature Biotechnology and then as Senior Editor at Nature Medicine. In November 2000, Rob was appointed the Editor and Director of Content Development of the biotechnology web portal Bio.com, based in Berkeley, California. He most recently was the Editorial Manager at LifeSpan Biosciences in Seattle. Rob is also a freelance writer for the Elsevier journal Chemistry and Biology. Rob is fluent in English and French and brings substantial experience in scientific publication. Rob will be based at Elsevier's offices in San Diego, California. The staff of Elsevier, the editorial board of Molecular Therapy, and the members of the American Society of Gene Therapy extend Rob Frederickson a very warm welcome! (Please continue to submit manuscripts to the New York office.)
The effect of aspirin on haemostatic activity in the treatment of chronic venous leg ulceration
Authors: S.H. IBBOTSON, A.M LAYTON, J.A DAVIES, M.J.D. GOODFIELD
Journal: British Journal of Dermatology (1995)

An increased rate of venous ulcer healing with the use of oral enteric‐coated aspirin (300mg) daily has been reported.1 Whether the effect of aspirin in this condition is related to its action on the haemostatic mechanism is unclear, and therefore this study aimed to assess the effect of aspirin on some haemostatic parameters in patients with chronic venous leg ulcers. A double‐blind, randomized, placebo‐controlled, parallel‐group study of haemostatic activity and the effect of aspirin was implemented over a 4‐month period. Twenty patients with venous leg ulcers, and 20 age‐ and sex‐matched controls were studied. Patients received enteric‐coated aspirin (300mg) or placebo (one tablet) daily for 4 months, in addition to standardized local compressive bandaging (Setopress®). Assessments made at recruitment, and at 2 and 4 months, included measurement of total ulcer surface area, haematological and biochemical screening, measurement of coagulation times, coagulation factor VIII:C (FVIII:C) and von Willebrand factor (vWF), and plasminogen activator inhibitor‐1 (PAJ‐1) levels. Procoagulant activity was assessed by a computer‐assisted technique, to determine the rate of thrombin production in vitro. Patients with venous ulcers had increased levels of fibrinogen (P < 0.01), FVIII:C (P < 0.05), vWF (P < 0.05) and PAI‐1 antigen (P < 0.01) compared with controls. Shortening of the coagulation rate, shown by a reduction of the time to generate 50% maxima! thrombin activity in seconds (T5o), was seen in patients, in comparison with control subjects (P < 0.05). T50 was longer in patients receiving aspirin than those receiving placebo, reflecting prolongation of coagulation rate in the aspirin‐treated group. In addition, an increased rate of ulcer healing occurred in subjects receiving aspirin compared with the placebo‐treated group (P < 0.01, P < 0.02 at 2 and 4 months, respectively). No significant change in fibrinogen, FVIII:C, vWF or PAI‐1 levels occurred in either group during the 4‐month period.
Lipotoxic disruption of NHE1 interaction with PI(4,5)P2 expedites proximal tubule apoptosis
Authors: Shenaz Khan, Bassam G. Abu Jawdeh, Monu Goel, William P. Schilling, Mark D. Parker, Michelle A. Puchowicz, Satya P. Yadav, Raymond C. Harris, Ashraf El-Meanawy, Malcolm Hoshi, Krekwit Shinlapawittayatorn, Isabelle Deschênes, Eckhard Ficker, Jeffrey R. Schelling
Journal: Journal of Clinical Investigation (2014)

Chronic kidney disease progression can be predicted based on the degree of tubular atrophy, which is the result of proximal tubule apoptosis. The Na+/H+ exchanger NHE1 regulates proximal tubule cell survival through interaction with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], but pathophysiologic triggers for NHE1 inactivation are unknown. Because glomerular injury permits proximal tubule luminal exposure and reabsorption of fatty acid/albumin complexes, we hypothesized that accumulation of amphipathic, long-chain acyl-CoA (LC-CoA) metabolites stimulates lipoapoptosis by competing with the structurally similar PI(4,5)P2 for NHE1 binding. Kidneys from mouse models of progressive, albuminuric kidney disease exhibited increased fatty acids, LC-CoAs, and caspase-2–dependent proximal tubule lipoapoptosis. LC-CoAs and the cytosolic domain of NHE1 directly interacted, with an affinity comparable to that of the PI(4,5)P2-NHE1 interaction, and competing LC-CoAs disrupted binding of the NHE1 cytosolic tail to PI(4,5)P2. Inhibition of LC-CoA catabolism reduced NHE1 activity and enhanced apoptosis, whereas inhibition of proximal tubule LC-CoA generation preserved NHE1 activity and protected against apoptosis. Our data indicate that albuminuria/lipiduria enhances lipotoxin delivery to the proximal tubule and accumulation of LC-CoAs contributes to tubular atrophy by severing the NHE1-PI(4,5)P2 interaction, thereby lowering the apoptotic threshold. Furthermore, these data suggest that NHE1 functions as a metabolic sensor for lipotoxicity.
Drug users in contact with general practice.
Authors: J R Robertson
Journal: BMJ (1985)

A group of heroin users who are in contact with a general practice in north west Edinburgh are described. The study group was younger and included more women than previous studies. These people used a large variety of drugs and mainly purchased them locally. Frequent and often prolonged abstinent periods occurred with no prescribed opiate treatment. The group had experienced a high rate of drug related medical disorders. All these points raise the possibility that opiate users who are known to general practitioners may be a distinctly different population from those who attend drug dependency clinics. The frequency of remission and the prevalence of polydrug use have profound implications for planning and evaluating an effective medical response.
Early interventions to prevent psychosis: systematic review and meta-analysis
Authors: M. R. Stafford, H. Jackson, E. Mayo-Wilson, A. P. Morrison, T. Kendall
Journal: BMJ (2013)

<b>Objective</b> To determine whether any psychological, pharmacological, or nutritional interventions can prevent or delay transition to psychotic disorders for people at high risk. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Embase, Medline, PreMedline, PsycINFO, and CENTRAL were searched to November 2011 without restriction to publication status. <b>Review methods</b> Randomised trials comparing any psychological, pharmacological, nutritional, or combined intervention with usual services or another treatment. Studies of participants with a formal diagnosis of schizophrenia or bipolar disorder were excluded. Studies were assessed for bias, and relevant limitations were considered in summarising the results. <b>Results</b> 11 trials including 1246 participants and eight comparisons were included. Median sample size of included trials was 81 (range 51-288). Meta-analyses were performed for transition to psychosis, symptoms of psychosis, depression, and mania; quality of life; weight; and discontinuation of treatment. Evidence of moderate quality showed an effect for cognitive behavioural therapy on reducing transition to psychosis at 12 months (risk ratio 0.54 (95% confidence interval 0.34 to 0.86); risk difference −0.07 (−0.14 to −0.01). Very low quality evidence for omega-3 fatty acids and low to very low quality evidence for integrated psychotherapy also indicated that these interventions were associated with reductions in transition to psychosis at 12 months. <b>Conclusions</b> Although evidence of benefits for any specific intervention is not conclusive, these findings suggest that it might be possible to delay or prevent transition to psychosis. Further research should be undertaken to establish conclusively the potential for benefit of psychological interventions in the treatment of people at high risk of psychosis.
Optic and Peripheral Neuropathy in Cuba-Reply
Authors: Michio Hirano
Journal: JAMA (1994)

In Reply.  —We appreciate the comments of Hedges et al regarding our article entitled 'Outbreak' of Optic and Peripheral Neuropathy in Cuba? We agree with Sadun 1 and Hedges et al that it can be difficult to distinguish the Cuban optic neuropathy from functional vision loss; in fact, some of the Cuban cases might be functional. In our study, we used the following features to diagnose optic neuropathy: central or centrocecal scotoma and at least two of the following three criteria: (1) loss of visual acuity (corrected to 20/40 or worse); (2) loss of color vision (missed two or more of six American Optical Hardy-Hand-Ritter plates); and (3) temporal pallor of the optic disc. Hedges et al concur with Sadun that the critical finding in Cubans affected with optic neuropathy is presence of nerve fiber layer (NFL) dropout in the maculopapillary bundle of the retina.  The NFL is composed of
Genomic Copy Number Determines Functional Expression of β-Defensin 2 in Airway Epithelial Cells and Associates with Chronic Obstructive Pulmonary Disease
Authors: Wim Janssens, Hilde Nuytten, Lieven J. Dupont, Johan Van Eldere, Severine Vermeire, Diether Lambrechts, Kristiaan Nackaerts, Marc Decramer, Jean-Jacques Cassiman, Harry Cuppens
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Copy number variations of the cluster of beta-defensin genes have been associated with psoriasis and inflammatory bowel disease. Controversy still exists on whether the beta-defensins genes determine susceptibility for chronic obstructive pulmonary disease (COPD).We investigated whether genomic copy number variations of the beta-defensin gene cluster have a functional role in airway epithelial cells and associate with the presence of COPD.Baseline and inflammatory induced transcript expression of DEFB4 was studied in nasal epithelial cell cultures and its effect on Pseudomonas aeruginosa inhibition was assessed. Subsequently, relevant functional cut-offs for copy numbers were used to explore associations with COPD in two independent case-control studies.Copy number variation in the beta-defensin encoding genes correlated with baseline mRNA DEFB4 expression levels (R(2) = 0.96; P = 0.02), with a plateau effect from five copies or more. Only when higher copy numbers of beta-defensin genes were present, transcription was significantly up-regulated by tumor necrosis factor-alpha (P < 0.0001), which resulted in better antimicrobial activity in vitro. When comparing healthy smokers with COPD patients, a copy number greater than or equal to 5 was associated with increased risk for COPD with an adjusted odds ratio of 1.8 (confidence interval, 1.1-2.8; P = 0.02), which was confirmed by a second independent case-control study.Genomic copy number variation of beta-defensin encoding genes has a functional role in airway epithelial cells, which may contribute to the pathogenesis of COPD.
Trend of Mortality From Cancer of the Breast
Authors: Arthur S. Kraus
Journal: JAMA (1965)

SHIMKIN<sup>1</sup>has commented on the nearly stable levels of the death rate, the incidence rate, and the survival rate for cancer of the breast in the United States in recent decades. The statistics he used were all total rates, adjusted for changes in the age distribution of the population, and he made no reference to trends in the rates for specific age groups. He infers from the stability of these ageadjusted total rates that etiologic, diagnostic, and therapeutic factors have remained either stationary or in a state of balance. As an example, he believes that the stable rates are evidence against importantetiologic roles for nonlactation or for use of exogenous estrogens, since it is believed that these factors have exhibited upward or downward trends. We have recently examined the trend of the age-color-specific death rates from cancer of the breast in the United States,<sup>2</sup>and these suggest
The Cardiomyopathy of Overload: An Unnatural Growth Response in the Hypertrophied Heart
Authors: Arnold M. Katz
Journal: Annals of Internal Medicine (1994)

Heart failure is a progressive condition with a 5-year survival of less than 50%. This poor prognosis, which can be reproduced by overloading the hearts of experimental animals, may reflect molecular abnormalities caused when overload stimulates adult cardiac myocytes to undergo hypertrophy. Because these terminally differentiated cells have little or no capacity to divide, hypertrophy represents an unnatural growth response; however, the mechanism by which overload shortens survival remains speculative. Modification of this unnatural growth response by converting enzyme inhibitors and nitrates, which have growth inhibitory as well as vasodilator effects, may contribute to the ability of these drugs to improve prognosis in patients with heart failure.
Primary Arterial Switch Operation as a Strategy for Total Correction of Taussig–Bing Anomaly
Authors: Denise A. Hayes, Sophie Jones, Jan M. Quaegebeur, Marc E. Richmond, Howard F. Andrews, Julie S. Glickstein, Jonathan M. Chen, Emile Bacha, Leonardo Liberman
Journal: Circulation (2013)

Studies of the arterial switch operation for Taussig-Bing anomaly demonstrate significant rates of reintervention and mortality, particularly after initial palliation to delay complete repair. We aimed to describe the long-term outcomes of our 21-year practice of single-stage arterial switch operation for all patients with Taussig-Bing anomaly.A retrospective study was performed, and 43 patients with Taussig-Bing anomaly were identified between 1990 and 2011. Median age at arterial switch operation was 7 (range, 2-192) days, and median operative weight was 3.2 (1.4-6.2) kg. Aortic arch obstruction was present in 30 patients (70%). Hospital mortality was 7% (n=3). Follow-up was available for 37 hospital survivors at a mean of 8.1 (± 6.3) years. Late mortality was 2% (n=1). At follow-up, all patients were in New York Heart Association functional class I. Freedom from transcatheter or surgical reintervention was 73% at 1 year, 64% at 5 years, and 60% at 10 years. Eleven patients underwent 13 catheter reinterventions on the pulmonary arteries (n=8) or aortic arch (n=5). Seven patients underwent 11 reoperations, including relief of right ventricular outflow tract obstruction (n=5), pulmonary arterioplasty (n=3), recoarctation repair (n=2), and tricuspid valve repair (n=1). By multivariate analysis, a preoperative aortic valve annulus z score of ≤-2.5 was associated with reintervention (hazard ratio, 7.66 [95% confidence interval, 1.29-45.6], P=0.03).Although reintervention is common, primary correction of Taussig-Bing anomaly with arterial switch operation can be achieved in all patients with low mortality and good long-term outcomes.
Co-ordination Between Clinical and Didactic Work.
Authors: Alfred Stengel.
Journal: JAMA (1904)

Philadelphia, Aug. 2, 1904. <h3>To the Editor:</h3> —May I avail myself of the opportunity, which your Educational Number will give, of expressing some views on medical education arrived at after a number of years' service as a teacher of clinical medicine? The remarks I shall have to make relate to the practical branches only; the teaching of the purely scientific subjects is quite another matter. I wish further to add that my remarks have reference to the senior year of study. Physical diagnosis, clinical pathology and history taken properly belong to the pre-senior years. It would be impossible to draw up an ideal scheme for the teaching of medicine and surgery without taking into consideration available material, its distribution and other local conditions, the number of students, etc. Whatever the conditions, there must be a co-ordination of different methods of teaching and a suitable apportionment of the student's time. When
Body fat and increased risk of cirrhosis
Authors: C. D Byrne, S H Wild
Journal: BMJ (2010)

Better diagnosis and treatment of non-alcoholic fatty liver disease are needed

Overweight (defined for European populations as a body mass index (BMI) of between 25 and <30) and obesity (defined as BMI ≥30) have become a considerable threat to public health worldwide.1 2 3 The prevalence of overweight and obesity continues to rise in most countries—for example, the proportion of over 16 year olds classified as obese in England rose from 15% in 1991 to 24% in 2007, and this has resulted in increased use of healthcare resources to treat the consequences of obesity.4 Established consequences of obesity include cardiovascular disease, diabetes, musculoskeletal problems, gallstones, and various cancers. In the linked studies, Liu and colleagues (doi:10.1136/bmj.c912)5 and Hart and colleagues (doi:10.1136/bmj.c1240)6 assess the link between BMI, alcohol intake, and liver disease.

Using data from a cohort of 1.2 million women within the Million Women Study, who had no liver disease or cancer at baseline, Liu and colleagues found that the relative risk of liver cirrhosis increased by 28% for every 5 unit increase in BMI above 22.5 in each stratum of alcohol consumption.5 Women were recruited between 1996 and 2001 at a mean age of 56 years from NHS breast screening centres in the United Kingdom, and they self reported height and weight (with measured data available for a subgroup). Data on hospital admissions and deaths were collected from record linkage after a mean of 6.2 years. Over this period, 1811 women had a first hospital admission or died from cirrhosis and the absolute risk of …
Urban-Oriented Methods
Authors: Julian A. Waller
Journal: JAMA (1973)

Rural communities are not merely miniaturized versions of cities and suburbs and, thus, require different approaches to emergency care than are relevant to urban areas. Emphasis should be placed first on improving capability to respond to emergencies that threaten life and limb rather than on responding to the much larger number of less serious events, inadequate care of which results in inconvenience only. Most persons who die unnecessarily could be saved with relatively simple techniques, and improvement of basic services and skills is much more important at this time than is development of highly sophisticated training programs and response systems. Emergency room nurses need better training, standard protocols for emergency response, and both nurses and ambulance personnel need frequent critique sessions to make up for the sparsity of real emergencies they see. Program evaluation must be an integral part of any improvement effort.
Cost-Effectiveness of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease
Authors: Kevin F. Erickson, Glenn M. Chertow, Jeremy D. Goldhaber-Fiebert
Journal: Annals of Internal Medicine (2013)

Chinese translationIn the TEMPO (Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes) trial, tolvaptan significantly reduced expansion of kidney volume and loss of kidney function.To determine how the benefits of tolvaptan seen in TEMPO may relate to longer-term health outcomes, such as progression to end-stage renal disease (ESRD) and death, and cost-effectiveness.A decision-analytic model.Published literature from 1993 to 2012.Persons with early autosomal dominant polycystic kidney disease.Lifetime.Societal.Patients received tolvaptan therapy until death, development of ESRD, or liver complications or no tolvaptan therapy.Median age at ESRD onset, life expectancy, discounted quality-adjusted life-years and lifetime costs (in 2010 U.S. dollars), and incremental cost-effectiveness ratios.Tolvaptan prolonged the median age at ESRD onset by 6.5 years and increased life expectancy by 2.6 years. At $5760 per month, tolvaptan cost $744 100 per quality-adjusted life-year gained compared with standard care.For patients with autosomal dominant polycystic kidney disease that progressed more slowly, the cost per quality-adjusted life-year gained was even greater for tolvaptan.Although TEMPO followed patients for 3 years, the main analysis assumed that clinical benefits persisted over patients' lifetimes.Assuming that the benefits of tolvaptan persist in the longer term, the drug may slow progression to ESRD and reduce mortality rates. However, barring an approximately 95% reduction in price, cost-effectiveness does not compare favorably with many other commonly accepted medical interventions.National Institutes of Health and Agency for Healthcare Research and Quality.