tbuckley/cabot-search huggingface dataset:
Origin and evolution of homologous repeated sequences in the mitochondrial DNA control region of shrews
Authors: L. Fumagalli, P. Taberlet, L. Favre, J. Hausser
Journal: Molecular Biology and Evolution (1996)

The complete mitochondrial DNA (mtDNA) control region was amplified and directly sequenced in two species of shrew, Crocidura russula and Sorex araneus (Insectivora, Mammalia). The general organization is similar to that found in other mammals: a central conserved region surrounded by two more variable domains. However, we have found in shrews the simultaneous presence of arrays of tandem repeats in potential locations where repeats tend to occur separately in other mammalian species. These locations correspond to regions which are associated with a possible interruption of the replication processes, either at the end of the three-stranded D-loop structure or toward the end of the heavy-strand replication. In the left domain the repeated sequences (R1 repeats) are 78 bp long, whereas in the right domain the repeats are 12 bp long in C. russula and 14 bp long in S. araneus (R2 repeats). Variation in the copy number of these repeated sequences results in mtDNA control region length differences. Southern blot analysis indicates that level of heteroplasmy (more than one mtDNA form within an individual) differs between species. A comparative study of the R2 repeats in 12 additional species representing three shrew subfamilies provides useful indications for the understanding of the origin and the evolution of these homologous tandemly repeated sequences. An asymmetry in the distribution of variants within the arrays, as well as the constant occurrence of shorter repeated sequences flanking only one side of the R2 arrays, could be related to asymmetry in the replication of each strand of the mtDNA molecule. The pattern of sequence and length variation within and between species, together with the capability of the arrays to form stable secondary structures, suggests that the dominant mechanism involved in the evolution of these arrays in unidirectional replication slippage.
Safety of Chloroquine in Pregnancy
Authors: Charles T. Stone
Journal: JAMA (1965)

<h3>To the Editor:—</h3> I have read with considerable interest a quotation from an article I wrote in 1962, which was quoted in the March 1, 1965, issue ofThe Journal(<b>191</b>: 765), in the letter, "Safety of Chloroquine in Pregnancy." I hope that the quotation, which is correct as stated, will not be taken as an endorsement for the use of chloroquine in the treatment of pregnant patients. We have used large quantities of antimalarial drugs, notably chloroquine and hydroxychloroquine in treatment of rheumatoid arthritis since approximately August of 1957. It is my personal belief that of the two drugs, chloroquine is more effective as an antiarthritic agent; but there is reason to believe that in our series of patients, one or two have sustained, perhaps, permanent damage to the retina; so that based upon our own experience, as well as that reported in the literature otherwise, we have completely
"Spontaneous Arterial Degeneration in Rabbits."
Authors: Joseph L. Miller
Journal: JAMA (1907)

Chicago, Nov. 7, 1907. <h3>To the Editor:</h3> —InThe Journal, Oct. 5, 1907, is an article by Dr. Miles and an editorial on the above subject. The suggestion is made in these articles that the various experimental vascular changes that have been produced during the past four years may be in reality of spontaneous origin. Jores' exhaustive dissertations on arteriosclerosis which appeared just previous to Josué's successful experimental work, reviews the various attempts to produce arterial changes in animals and especially in rabbits, and the total number of animals carefully examined must have been large and yet in not one of these were they able to detect vascular changes. In 1900 Crofton reported atheroma in two rabbits as a result of injections with hypoxanthin. Fisher, while working with adrenalin arteriosclerosis, reports that in some poorly nourished animals he found slight spontaneous changes resembling those produced by adrenalin. Ophüls, also, recently
Treatment of COPD and the TOnado trial: a tempest in a teapot?
Authors: Klaus F. Rabe
Journal: European Respiratory Journal (2015)

The treatment of COPD follows a stepwise approach in practically all clinical practice guidelines and also current strategy documents [1]. Lung function impairment or low forced expiratory volume in 1 s (FEV1), once considered the single most important treatment parameter, now represents one of the target parameters for risk reduction in patients with chronic obstructive pulmonary disease (COPD), alongside exacerbations and respiratory symptoms, dyspnoea in particular. Furthermore, more holistic COPD approaches increasingly recognise the importance of physical activity and multimorbidity for disease outcome, mortality in particular [2]. Despite encouraging results for LABA/LAMA combination therapy in mild COPD, can we justify the additional costs? <http://ow.ly/JVNb6>
Effect of the Asp <sup>298</sup> Variant of Endothelial Nitric Oxide Synthase on Survival for Patients With Congestive Heart Failure
Authors: Dennis M. McNamara, Richard Holubkov, Lisa Postava, Ravi Ramani, Karen Janosko, Michael Mathier, Guy A. MacGowan, Srinivas Murali, Arthur M. Feldman, Barry London
Journal: Circulation (2003)

Significant variation exists within the endothelial nitric oxide synthase (NOS3) gene that may influence cardiovascular risk. The Asp298 variant of NOS3 has a shorter half-life in endothelial cells. Given the importance of nitric oxide in the heart failure syndrome, we evaluated the effect of this variant on event-free survival in a population with systolic dysfunction.Four hundred sixty-nine patients (72% male, 49% ischemic; mean age, 56+/-12 years) with systolic dysfunction (left ventricular ejection fraction < or =0.45) were enrolled in a study of Genetic Risk Assessment of Cardiac Events (GRACE). The polymorphism in exon 7 of NOS3, a G-T transition at position 894 that results in a Glu to Asp amino acid substitution for codon 298, was genotyped and subjects were followed prospectively to the end point of death or heart transplantation. Event-free survival was compared on the basis of the presence (group 1, n=266) or absence (group 2, n=203) of the Asp298 variant. Event-free survival was significantly poorer in patients with the Asp298 variant (percent event-free survival group 1 at 1/2/3 years=78/65/54; group 2=82/72/64, P=0.03). In subset analysis, the adverse impact of the Asp298 variant was primarily in patients with nonischemic cardiomyopathy (group 1=82/73/63; group 2=87/79/71, P=0.03) and was not apparent among patients with ischemic heart disease (group 1=75/59/47; group 2=74/62/54, P=0.71).For patients with heart failure caused by systolic function, the Asp298 variant of NOS3 is associated with poorer event-free survival, particularly in patients with nonischemic cardiomyopathy.
Diacylglycerol Production, Ca<sup>2+</sup>Influx, and ProteinKinase C Activation in Sustained Cellular Responses*
Authors: HOWARD RASMUSSEN, CARLOS M. ISALES, ROBERTO CALLE, DOUGLAS THROCKMORTON, MATTHEW ANDERSON, JOSE GASALLA-HERRAIZ, RICHARD McCARTHY
Journal: Endocrine Reviews (1995)

THE focus of this review is on the role of protein kinase C (PKC) in the regulation of the secretion of aldosterone from the adrenal glomerulosa cell and of insulin from the β-cell of the Islets of Langerhans. These processes will be considered in the context of a model of how PKC functions as one component of a three-component, Ca2+-influx-diacylglycerol (DAG)-PKC, plasma membrane transducer involved in regulation of the sustained phase of these secretory responses. Within this context, the possible role of this transducer in the phenomenon of time-dependent potentiation (TDP) and time-dependent suppression (TDS) of these responses will also be considered. The initial physiological system in which the activation of PKC was reported to play a signaling role was that of platelet activation. In their initial studies, Takai et al. (1) showed that activation of both the calcium-calmodulin-dependent myosin light chain kinase, and PKC, a phospholipid- and calcium ion-dependent enzyme, were necessary for the full platelet response. They proposed that the activation of these two kinases were coincident events. This proposal was in keeping with the then current concept that when an extracellular messenger interacts with its receptor, intracellular messengers are produced that act concurrently to produce a cellular response. They proposed that the activation of these two kinases were coincident events. This proposal was in keeping with the then current concept that when an extracellular messenger interacts with its receptor, intracellular messengers are produced that act concurrently to produce a cellular response. In this view, hormone-receptor interaction is somewhat analogous to turning on and off a light switch, i.e. an intracellular signal of constant strength is produced as long as the switch is turned on, and once it is turned off, this system rapidly relaxes back to its original state. However, from more recent studies of cell activation, it has become clear that in many instances there is a temporal progression of signaling events when a cell is activated by an extracellular messenger. Thus, rather than operating more or less as a light switch, the activated receptor operates in a fashion analogous to the activation of a programmed tape of instructions. In this way, cells tell time, i.e. cell signaling is an historical process (2). In addition, our models of how signaling pathways regulate cellular responses have gone from the simple to the complex.
901-51 Three Dimensional Reconstruction Using a New Dual Axis Multiplane Transesophageal Echo Probe: Calculation of Left Ventricular Volume
Authors: Malcolm E. Legget, Roy W. Martin, Florence H. Sheehan, Gerry Bashein, Edward L. Bolson, Xian-Ning Li, John A. McDonald, Ram Hatangadi, Catherine M. Otto
Journal: Journal of the American College of Cardiology (1995)
Glucagon therapy in acute pancreatitis. Report of a double-blind trial.
Authors: H K Durr, D Maroske, O Zelder, J C Bode
Journal: Gut (1978)

The results of a double-blind trial of glucagon in 69 patients with acute pancreatitis are reported. In a subgroup of 59 patients statistical analysis showed no significant differences between the glucagon-treated (n = 29; 2 X 5 mg protamine-zinc glucagon intramuscularly per day) and the placebo-treated (n = 30) subjects for the following data: duration of pain left spontaneously and induced by palpation, amounts of analgesics and antispasmodics required by the patients, duration of hospital stay, amylase activities in serum and 24 hour urine collections. Mortality rates did not differ significantly between the glucagon-treated and the placebo-treated subjects in the total group of 69 patients and in the two subgroups of patients who were treated conservatively (n = 59) and those who underwent laparotomy because of severe peritonitis (n = 10). From the results of this study it is concluded that favourable effects of glucagon upon the course of acute pancreatitis--if they do exist--are not significant.
OBSERVATIONS ON THE SURFACE FLORA OF THE SKIN AND ON THE SKIN pH
Authors: W. C. NOBLE
Journal: British Journal of Dermatology (1968)

SUMMARY. —The skin surface flora of 204 individuals was investigated quantitatively at 6 sites, using the Sellotape stripping method. In 51 of these individuals the skin pH was also measured. There were significant differences between individuals in the number of bacteria recovered but not between sites. Significantly greater numbers of bacteria were recovered from females than from males. The skin pH readings showed small but significant differences between individuals and between sites, but no correlation could be demonstrated between pH and bacterial count.
Prospective study of symptoms and signs in acutely ill infants in general practice.
Authors: A Wright, G H Luffingham, D North
Journal: BMJ (1987)

A study was made of all cases of acute illness in infants aged 6 months or less presenting in a Gosport practice over five months. The frequency in these patients of the well defined symptoms and signs suggested to be important by the preliminary report of the Department of Health and Social Security's multicentre study of postneonatal mortality was recorded. During the study period there were 161 infants of this age in the practice, who gave rise to 69 consultations with acute illness. Thirty eight of these were given drug treatment and five were referred to a paediatric unit, one of them on social grounds. There were no infant deaths in the practice (total population 11,400), but two occurred in the Gosport area (total population 83,000). It would be unrealistic to refer all patients with any one of the symptoms and signs, even when well defined, in the age group 6 months or less. Analysis of the symptoms and signs found in those children who required admission did not show any pattern differentiating them from those who did not. Although the symptoms and signs studied are of value in assessment and should be sought in these patients, they cannot be used singly or in any pattern to indicate referral per se.
An Additional Basic Science for Clinical Medicine: III. The Challenges of Comparison and Measurement
Authors: ALVAN R. FEINSTEIN
Journal: Annals of Internal Medicine (1983)

The main scientific virtue of randomized allocation of treatment is an unpredictability that reduces susceptibility bias in the groups created when treatments are assigned preferentially according to prognostic differences. Even in randomized trials, however, prognostic analyses are needed for checking imbalances in the randomization, for precise clinical application of results, and for discerning disparate therapeutic effects. Improved methods of prognostic analyses can enhance effectiveness in randomized trials and credibility for nonrandomized therapeutic comparisons. Regardless of randomization, therapeutic comparisons will also be improved with better analysis of proficiency for the main treatments, better attention to identifying "soft" clinical outcome events, and development of new analytic structures for complex problems in logistics. The challenges will require better scientific methods for the two types of clinical measurement: the mensuration with which descriptive expressions are provided for individual observations; and the quantification with which individual descriptions are grouped, summarized, and compared.
Safety in New Drugs
Authors: Walter Modell
Journal: JAMA (1964)

NOW, BY LAW, new drugs must be both effective and relatively safe. But I think a new drug must be more than a tolerable cipher in an already overcrowded list. The hope of significant new knowledge which may lead to therapeutic progress is, in my view, the only defense for studying the effects of as yet poorly understood new drugs in human subjects. How can we determine that a new drug will make therapeutic progress? To designate the processes involved in arriving at such a judicious decision, the new drug regulations use legal phaseology ( one of my favorite private puns), phase I, phase II, and phase III. This whole important problem would be more provocative, I believe, if the separate issues were made more graphic, less legal, less rigid, and, so it seems to me, more meaningful and more flexible. Since "safety" and "therapeutic effectiveness" are not legal catch phrases
Allergic symptoms up to 4–6 years of age in children given cow milk neonatally A prospective study
Authors: A.T. B. Lindfors, L. Danielsson, E. Enocksson, S. G. O. Johansson, S. Westin
Journal: Allergy (1992)

In a previously published prospective study, we followed the development of allergic symptoms in term infants with a slightly reduced birthweight (-1 SD to -2 SD). These children received, according to local routine, early feeding with cow milk formula in order to diminish such neonatal problems as hypoglycemia and hyperbilirubinemia. Of 216 infants 207 were observed for allergic symptoms up to 18 months of age. One group (F) received cow milk formula during the first days of life before the mother's breastmilk production started and was then breastfed; the other (B) was not given any formula before normal breastfeeding started. Unexpectedly, we found fewer allergic symptoms, in particular allergic skin problems, in the group fed cow milk, the difference being concentrated to children with a family history of allergic symptoms. At 5 years of age 183 of the 207 children have been reinvestigated. Mild symptoms of allergy (suspected and obvious) were found in 22% (F) and 27% (B) respectively (NS). Moderate and severe symptoms of allergy (obvious) were found in 4.2% (F) and 4.5% (B). In the subgroup with a double family history of allergic symptoms, 28% (7/25, F) and 59% (10/17, B) had symptoms of allergy (p less than 0.05). This difference was even more pronounced when laboratory tests in favour of atopic diagnosis were included, 14% (F) and 53% (B) respectively (p less than 0.05). Thus at 5 years we still find a significantly lower frequency of allergic symptoms in the subgroup fed cow milk formula early with a family history of allergic symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
PU.1 Functions in a Cell-Autonomous Manner to Control the Differentiation of Multipotential Lymphoid–Myeloid Progenitors
Authors: Edward W Scott, Robert C Fisher, Marilyn C Olson, Eli W Kehrli, M.Celeste Simon, Harinder Singh
Journal: Immunity (1997)

Transcription factor PU.1 is required for the development of lymphoid and myeloid progenitors during fetal hematopoiesis. By generating chimeric animals using PU.1−/− ES cells or PU.1−/− hematopoietic progenitors, we demonstrate that PU.1 functions in an exclusively cell-autonomous manner to regulate the development of the lymphoid–myeloid system. Multipotential lymphoid–myeloid progenitors (AA4.1+, Lin−) are significantly reduced in PU.1−/− embryos and fail to differentiate into B lymphoid or myeloid cells in vitro. These results suggest that the lymphoid and myeloid lineages develop in the fetal liver from a common hematopoietic progenitor not shared with erythrocytes and megakaryocytes. Finally, the Ikaros gene is expressed in PU.1 mutant embryos, suggesting that PU.1 and Ikaros are independently required for specification of embryonic lymphoid cell fates.
The clinical transition between pemphigus foliaceus and pemphigus vulgaris correlates well with the changes in autoantibody profile assessed by an enzyme-linked immunosorbent assay
Authors: A. Komai, M. Amagai, K. Ishii, T. Nishikawa, T. Chorzelski, I. Matsuo, T. Hashimoto
Journal: British Journal of Dermatology (2001)

Background There are a number of reports of pemphigus with clinical shifting between pemphigus foliaceus (PF) and pemphigus vulgaris (PV). On the other hand, a novel enzyme‐linked immunosorbent assay (ELISA) against recombinant baculoproteins of desmoglein 1 (Dsg1) (PF antigen) and Dsg3 (PV antigen) has been established and found to be extremely sensitive and specific. Objectives To characterize the change in the antibody profiles in a series of pemphigus cases with mixed features of PF and PV by various methods, including the novel ELISA. Patients/methods Sera were obtained from eight cases undergoing a shift between PF and PV and three cases of coexistent PF and PV. The autoantigens were analysed by ELISA, as well as by immunofluorescence using normal human skin sections and immunoblotting using normal human epidermal extracts. Results The results of the ELISA, immunofluorescence and immunoblotting studies showed that the transition between PF and PV correlates well with the changes of autoantibodies against either Dsg1 or Dsg3. Conclusions The clinical phenotype at each stage is defined by the anti‐Dsg antibody profile in the serum of these pemphigus patients showing mixed features of PF and PV. In addition, ELISA using recombinant baculoproteins was particularly useful in distinguishing PF and PV.
Naproxen and Ejaculatory Dysfunction
Authors: Nathan Wei, Jerry C. Hood
Journal: Annals of Internal Medicine (1980)

Letters and Corrections1 December 1980Naproxen and Ejaculatory DysfunctionNATHAN WEI, M.D., JERRY C. HOOD, M.S.NATHAN WEI, M.D.Search for more papers by this author, JERRY C. HOOD, M.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-93-6-933_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Second generation nonsteroidal anti-inflammatory agents have been associated with a relative lack of serious adverse reactions. Although many minor side effects have been documented, no reports have linked naproxen therapy with male sexual dysfunction. The following is a case report of such an apparent side effect.A 66-year-old man presented with a 2-year history of generalized arthralgias that increased in severity during the 3 or 4 months before examination. The patient admitted to having joint stiffness of one-half hour's duration every morning but denied having dry eyes, dry mouth, parotid gland enlargement, rash, alopecia, or evidence of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPain Medications and Male ReproductionNaproxen and piproxenFármacos e infertilidad: revisiónNON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)NaproxenAnti-inflammatory analgesics and drugs used in rheumatoid arthritis and gout 1 December 1980Volume 93, Issue 6Page: 933-933KeywordsAdverse reactionsArthralgiaMouthNSAIDsParotid glandsRashesSexual dysfunctionStiffness Issue Published: 1 December 1980 PDF DownloadLoading ...
Correlations between epithelial cells and bacterial populations in bacteriological skin samples
Authors: MOLLIE E. McBRIDE, W. CHRISTOPHER DUNCAN, JOHN M. KNOX
Journal: British Journal of Dermatology (1978)

Journal Article Correlations between epithelial cells and bacterial populations in bacteriological skin samples Get access MOLLIE E. McBRIDE, MOLLIE E. McBRIDE Department of Dermatology, Baylor College of Medicine, 1200 Moursund Avenue, Houston, Texas 77030, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar W. CHRISTOPHER DUNCAN, W. CHRISTOPHER DUNCAN Department of Dermatology, Baylor College of Medicine, 1200 Moursund Avenue, Houston, Texas 77030, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar JOHN M. KNOX JOHN M. KNOX Department of Dermatology, Baylor College of Medicine, 1200 Moursund Avenue, Houston, Texas 77030, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 99, Issue 5, 1 November 1978, Pages 537–543, https://doi.org/10.1111/j.1365-2133.1978.tb02022.x Published: 01 November 1978
Salaries in Occupational Medicine
Authors: R. E. W. Fisher
Journal: BMJ (1974)

11337 (48 %) of the women were known to have 'stopped taking the pill, 7,563 (320%,) were lost or withdrawn, and only 4,711 (20%) were known to be still taking the pill at the time of the final analysis.The main reason given for stopping the pill was iinter- current morbidity (33.6%).This was mostly depression and headaches.However, it is stated, "the report shows that only in a small fractilon of these diseases is there any