tbuckley/cabot-search huggingface dataset:
Stimulation of Protein Kinase C Inhibits Bursting in Disease-Linked Mutant Human Cardiac Sodium Channels
Authors: M. Tateyama, J. Kurokawa, C. Terrenoire, I. Rivolta, R.S. Kass
Journal: Circulation (2003)

Background— Mutations in SCN5A , the gene coding for the human cardiac Na + channel α-subunit, are associated with variant 3 of the long-QT syndrome (LQT-3). Several LQT-3 mutations promote a mode of Na + channel gating in which a fraction of channels fail to inactivate, contributing sustained Na + channel current ( I sus ), which can delay repolarization and prolong the QT interval. Here, we investigate the possibility that stimulation of protein kinase C (PKC) may modulate I sus , which is prominent in disease-related Na + channel mutations. Methods and Results— We measured the effects of PKC stimulation on Na + currents in human embryonic kidney (HEK 293) cells expressing 3 previously reported disease-associated Na + channel mutations (Y1795C, Y1795H, and ΔKPQ). We find that the PKC activator 1-oleoyl-2-acetyl- sn -glycerol (OAG) significantly reduced I sus in the mutant but not wild-type channels. The effect of OAG on I sus was reduced by the PKC inhibitor staurosporine (2.5 μmol/L), ablated by the mutation S1503A, and mimicked by the mutation S1503D. I sus recorded in myocytes isolated from mice expressing ΔKPQ channels was similarly inhibited by OAG exposure or stimulation of α 1 -adrenergic receptors by phenylephrine. The actions of phenylephrine on I sus were blocked by the PKC inhibitor chelerythrine. Conclusions— We conclude that stimulation of PKC inhibits channel bursting in disease-linked mutations via phosphorylation-induced alteration of the charge at residue 1503 of the Na + channel α-subunit. Sympathetic nerve activity may contribute directly to suppression of mutant channel bursting via α-adrenergic receptor–mediated stimulation of PKC.
Studies of percutaneous epididymal sperm aspiration (PESA) and intracytoplasmic sperm injection
Authors: G. Meniru
Journal: Human Reproduction Update (1998)

Four distinct studies were carried out using two data sets of percutaneous epididymal sperm aspiration (PESA) and intracytoplasmic sperm injection (ICSI) procedures performed from March 1993 to January 1997. In study A, an analysis of 181 ICSI treatment cycles following PESA revealed a successful epididymal sperm retrieval rate of 83%. It confirmed that PESA is an effective sperm retrieval method and the associated ICSI pregnancy rate (35% per embryo transfer) compared favourably with that of other sperm retrieval methods. In study B, the relevance of a prior diagnostic PESA procedure was ascertained by comparing the sperm retrieval rates in two groups of patients having their first ICSI treatment cycle with spermatozoa retrieved through PESA. Group B1 (n=50) had diagnostic PESA prior to the ICSI treatment cycle PESA procedure, unlike patients in group B2 (n=64) who did not. The sperm retrieval rate in the treatment cycle procedure was not different at 90 and 82.8% for groups B1 and B2 respectively. However, the discontinuation of diagnostic PESA is fraught with problems including liability to medico-legal sanctions. In study C, analysis of 177 treatment cycles involving PESA and ICSI revealed a successful sperm retrieval rate by PESA of 82% in the first cycle, 93% in the second, 96% in the third and 100% in the fourth cycle. The same trend was evident when sperm retrieval was examined in relation to each of the epididymides. Retrieved spermatozoa were found to be motile in 67-100% of cases and the frequency of samples containing motile spermatozoa did not decrease with increase in the number of PESA attempts. These results show that PESA does not jeopardize future epididymal sperm retrieval. In study D, the outcome of treatment with ICSI using ejaculated spermatozoa (305 cycles) (group D1) was compared with that of ICSI using spermatozoa obtained through PESA (54 cycles) (group D2). The median age of women in the two groups of couples was similar (34 years). In group D1, 70% of metaphase II oocytes were fertilized compared with 61% in group D2 (P<0.01). The cleavage rate and the median numbers of transferred and cryopreserved embryos were similar in both groups. There was no significant difference between the clinical pregnancy rates (33 and 42% in groups D1 and D2 respectively). Our results show that the outcome of PESA-ICSI treatment compared favourably with that of ICSI using ejaculated spermatozoa.
Gene Expression Profiles of Acute Exacerbations of Idiopathic Pulmonary Fibrosis
Authors: Kazuhisa Konishi, Kevin F. Gibson, Kathleen O. Lindell, Thomas J. Richards, Yingze Zhang, Rajiv Dhir, Michelle Bisceglia, Sebastien Gilbert, Samuel A. Yousem, Jin Woo Song, Dong Soon Kim, Naftali Kaminski
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: The molecular mechanisms underlying acute exacerbations of idiopathic pulmonary fibrosis (IPF) are poorly understood. We studied the global gene expression signature of acute exacerbations of IPF.Objectives: To understand the gene expression patterns of acute exacerbations of IPF.Methods: RNA was extracted from 23 stable IPF lungs, 8 IPF lungs with acute exacerbation (IPF-AEx), and 15 control lungs and used for hybridization on Agilent gene expression microarrays. Functional analysis of genes was performed with Spotfire and Genomica. Gene validations for MMP1, MMP7, AGER, DEFA1–3, COL1A2, and CCNA2 were performed by real-time quantitative reverse transcription-polymerase chain reaction. Immunohistochemistry and in situ terminal deoxynucleotidyltransferase dUTP nick end-labeling assays were performed on the same tissues used for the microarray. ELISA for α-defensins was performed on plasma from control subjects, patients with stable IPF, and patients with IPF-AEx.Measurements and Main Results: Gene expression patterns in IPF-AEx and IPF samples were similar for the genes that distinguish IPF from control lungs. Five hundred and seventy-nine genes were differentially expressed (false discovery rate < 5%) between stable IPF and IPF-AEx. Functional analysis of these genes did not indicate any evidence of an infectious or overwhelming inflammatory etiology. CCNA2 and α-defensins were among the most up-regulated genes. CCNA2 and α-defensin protein levels were also higher and localized to the epithelium of IPF-AEx, where widespread apoptosis was also detected. α-Defensin protein levels were increased in the peripheral blood of patients with IPF-AEx.Conclusions: Our results indicate that IPF-AEx is characterized by enhanced epithelial injury and proliferation, as reflected by increases in CCNA2 and α-defensins and apoptosis of epithelium. The concomitant increase in α-defensins in the peripheral blood and lungs may suggest their use as biomarkers for this disorder.
Effect of hypercapnia on coronary circulation
Authors: D. ELIADES, H. R WEISS
Journal: Cardiovascular Research (1986)

The relative importance of hypercapnia in the control of coronary circulation was examined in 42 anaesthetised open chest rabbits. Coronary blood flow was determined with 15 μ.m radioactive microspheres. When mean (SD) Paco2 was increased from 38(10) to 76(16) mmHg in six rabbits, the hypercapnia caused a 62% increase in coronary blood flow. When a similar degree of metabolic acidosis was induced in 12 rabbits for either 15 or 60 min, no changes in coronary blood flow occurred. No increases in coronary blood flow occurred during hypercapnia with propranolol, 2 mg/kg (n=12), with or without atrial pacing to maintain heart rate. Similarly, carotid denervation prevented the carbon dioxide induced increase in coronary blood flow in six rabbits. Haemodiluted rabbits (n=6) with a 40% replacement of blood showed no changes in coronary blood flow with hypercapnia. This was due to the 22% decrease in systolic pressure-time index, despite their intact sympathetic nervous system and reduced Bohr shift. Therefore, although carbon dioxide is a coronary vasodilator, both direct vasodilatation and sympathetic adrenergic activation must be intact in order for coronary blood flow to be increased.
Quantitative studies of human urinary excretion of uropontin
Authors: Wei Min, Hiroshi Shiraga, Charles Chalko, Stanley Goldfarb, G. Gopal Krishna, John R. Hoyer
Journal: Kidney International (1998)

Uropontin is the urinary form of osteopontin, an aspartic acid-rich phosphorylated glycoprotein. Uropontin has been previously shown to be a potent inhibitor of the nucleation, growth and aggregation of calcium oxalate crystals and the binding of these crystals to renal epithelial cells. Quantitative data defining the excretion of this protein are necessary to determine its role in urinary stone formation. In the present studies, we determined uropontin excretion rates of normal humans. Urine samples were obtained under conditions of known dietary intake from young adult human volunteers with no history, radiographic or laboratory evidence of renal disease. Urinary concentrations of uropontin were measured by a sensitive ELISA employing an affinity purified polyclonal antiserum to uropontin. Thirteen normal subjects ingested a constant diet providing 1 gram of calcium, 1 gram of phosphorus, 150 mEq of sodium and 1 gram of protein per kilogram of body wt per day during an eight day study period. The relationship of urinary volume to uropontin excretion was assessed by varying fluid intake on the last four days of the study to change the mean urine volume/24 hr by > 500 ml. Urine collected in six hour aliquots for eight days was analyzed for uropontin by ELISA, and for calcium, and creatinine. Daily uropontin excretion of 13 individual subjects was 3805 +/- 1805 micrograms/24 hr (mean +/- 1 SD). The mean urinary levels (1.9 micrograms/ml) detected in the present study are sufficient for inhibition of crystallization; our previous studies have demonstrated that the nucleation, growth and aggregation of calcium oxalate crystals and their binding to renal cells in vitro are inhibited by this concentration of purified uropontin. In contrast to the regular pattern of diurnal variation of calcium excretion seen in most subjects, uropontin excretion showed no regularity of diurnal variation and was not directly related to either calcium or creatinine excretion or changes in urinary volume. However, uropontin concentration varied inversely with urine volume (P < or = 0.001), so that the highest uropontin concentrations occurred when urine volume was the lowest. We conclude that the physiologic characteristic of an inverse relationship of uropontin concentration to urine volume favors protection from urinary crystallization of calcium oxalate by uropontin. Our quantitative definition of urinary uropontin excretion of normal adults provides the basis for the evaluation of uropontin excretion by individuals who have formed urinary stones.
Bone mineral density in relation to polymorphism at the vitamin D receptor gene locus.
Authors: F G Hustmyer, M Peacock, S Hui, C C Johnston, J Christian
Journal: Journal of Clinical Investigation (1994)

Polymorphism at the vitamin D receptor gene was examined in relation to bone mineral density (BMD) at spine, femur, and forearm in 86 monozygotic (MZ) and 39 dizygotic (DZ) adult female twins. All were white, 63 pairs (44 MZ, 19 DZ) were premenopausal, and 43 pairs (31 MZ, 12 DZ) were discordant for age at menopause or use of estrogen. Each individual of the DZ pairs and one individual of MZ pairs was genotyped for ApaI, BsmI, and TaqI polymorphism at the vitamin D receptor gene locus using Southern hybridization. Intraclass correlations for BMD in MZ and DZ twin pairs indicated that heritability accounted for over 70% of BMD. There was no relationship between genotype for any of the three polymorphisms and BMD at any skeletal site in the twin population, considered either as a total population, both with and without twins discordant for age at menopause or use of estrogen, or as a premenopausal population. In DZ twin pairs discordant for alleles for the three polymorphisms, no allele was associated with higher or lower BMD. It is concluded that in this population of healthy adult females there was no relationship between these polymorphisms at the vitamin D receptor gene locus and BMD.
Severe molluscum contagiosum infection in a patient with human T cell lymphotrophic (HTLV-III) disease
Authors: Robert R. Redfield, William D. James, D. Craig Wright, Charles Brown, Syed Zaki Salahuddin, Phillip D. Markham, M.G. Sarngadharan, Thomas F. Folks, RobertC. Gallo
Journal: Journal of the American Academy of Dermatology (1985)
Toll-like Receptor 4 Mediates Innate Immunity to Kaposi Sarcoma Herpesvirus
Authors: Dimitrios Lagos, Richard James Vart, Fiona Gratrix, Samantha Jane Westrop, Victoria Emuss, Ping-Pui Wong, Rebecca Robey, Nesrina Imami, Mark Bower, Frances Gotch, Chris Boshoff
Journal: Cell Host & Microbe (2008)
HPV vaccination in the UK
Authors: Jo Waller, Jane Wardle
Journal: BMJ (2008)

Acceptable uptake is possible in schools, but important practical barriers exist 

In the accompanying study, Brabin and colleagues report findings from a pilot study of routine human papillomavirus (HPV) vaccination in advance of the implementation of a £100m (€124m; $197m) national HPV immunisation programme in the United Kingdom this autumn.1 The study achieved 70.6% uptake for the first dose of the vaccine, with a drop of only 2.1% for the second dose. The third dose has yet to be delivered, and the authors emphasise the crucial importance of maintaining high uptake for the final dose.

These are the first published data on the uptake of HPV vaccine, and they are both encouraging and consistent with studies of intentions to vaccinate in the UK and elsewhere.2 3 4 However, uptake was lower than the 87.2% achieved in the same age group for a school based meningitis C catch-up programme in 2000,5 or the 91% uptake of the first dose in a comparable study of hepatitis B vaccination. 1

Achieving acceptable coverage in the absence of national …
Motor Vehicles, Hypoglycemia, and Diabetic Drivers
Authors: Robert E Ratner, Fred W Whitehouse
Journal: Diabetes Care (1989)

Individuals with diabetes are increasingly persuing employment in fields previously restricted as a result of the development of chronic complications. Improved glycemic control resulting from use of sophisticated insulin delivery and monitoring systems has also led to the recognition of recurrent hypoglycemia as a potential major clinical and occupational hazard. No data concerning the occupational safety of individuals with insulin-treated diabetes mellitus (ITDM) are available. We review the literature on diabetic drivers in an effort to examine the impact of certification of ITDMs as commercial drivers. In the absence of significant worldwide experience with ITDMs as commercial drivers, the discussion is necessarily based on projected accident rates derived from data on frequency of hypoglycemia. These studies are universally flawed by variable definitions of hypoglycemia, ascertainment bias, and patient selection. They do, however, provide a worst-case/best-case scenario for discussion. It is imperative that any expansion of employment opportunities for ITDMs be followed carefully with prospective studies to assess the impact on public safety.
Antibiotic Resistance—Squeezing the Balloon?
Authors: John P. Burke
Journal: JAMA (1998)

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
SPONTANEOUS SURGICAL EMPHYSEMA IN CHILDREN
Authors: A. G. Watkins
Journal: BMJ (1936)

MEDICINE(With Special Plate) Spontaneous surgical emphysema in children-is uncommon, and Rolleston' has stated that in thirty years' experience of fever hospital practice he has seen " barely half a dozen cases " with this complication.It most often occurs in association with whooping-cough, measles, diphtheritic laryngeal obstruction, and bronchopneumonia, the last-named occurring along with the above or independently of them.Other conditions with which it
PARINAUD'S INFECTIOUS CONJUNCTIVITIS
Authors: E. A. Waldeck
Journal: JAMA (1924)

Since 1888, when Parinaud first described this form of conjunctivitis, very few instances have been reported. It was my good fortune to study such a case. <h3>REPORT OF CASE</h3> An American school girl, aged 13 years, came to the office, Nov. 22, 1923, with a swelling of the left upper eyelid and the left side of the face which had been present for the past three weeks. The condition started about four weeks previously as a "cold in the left eye," characterized by redness of the conjunctiva, tearing, and the adhesion of the lids by a purulent discharge in the morning. In a few days, this acute inflammatory condition of the left eye subsided, but the upper lid began to swell, and continued to do so until the ptosis interfered with vision. One week after the swelling in the lid began, a swelling started in the left preauricular region, which
Mice With a Deletion in the First Intron of the <i>Col1a1</i> Gene Develop Age-Dependent Aortic Dissection and Rupture
Authors: Otto Rahkonen, Ming Su, Harri Hakovirta, Ilpo Koskivirta, Sheriar G. Hormuzdi, Eero Vuorio, Paul Bornstein, Risto Penttinen
Journal: Circulation Research (2003)

The functional significance of the first intron of the Col1a1 gene in regulation of type I collagen synthesis remains uncertain. A previous study in mice established that a mutated Col1a1 allele that lacked a large fraction of the first intron, but retained the sequences required for normal splicing, was subject to an age- and tissue-dependent decrease in expression. In this study, we report that mice homozygous for this deletion are predisposed to dissection and rupture of the aorta during their adult life. Aortic dissection was not detected in autopsies of heterozygous animals or their littermate controls. Electron micrographs revealed fewer collagen fibrils and less compacted, irregular elastic lamellae in the aortic walls of homozygous mutant animals. Northern analysis of aortic RNA from 2.5- and 12-month-old homozygous mutant mice revealed that Col1a1 mRNA levels were decreased by 29% and 42%, respectively, relative to those of control littermates. In 12-month-old heterozygotes, the decrease was 32%. Allele-specific amplification of heterozygous cDNAs demonstrated that this reduction was limited to transcripts from the mutant allele. The collagen content of the aortas of homozygous mutant mice was also significantly lower in comparison to that of age-matched, control animals. These data establish that the integrity of the aortic wall depends on an adequate content of type I collagen, and that continued synthesis of collagen in the aorta as a function of age is critically dependent on sequences in the first intron of the Col1a1 gene.
A CASE OF DOUBLE GANGRENE OF LEGS FOLLOWING A MILD ATTACK OF ENTERIC FEVER
Authors: A. Dodds
Journal: BMJ (1903)

GANGRENE FOLLOWIN(G ENTERIC FEVER.m 1s a I 271 resulted.It will be seen that carbon electrodes charged with iron or cadmium have twice the bactericidal effect of ordinary carbons, and the cadmium electrodes appear to be preferable to the iron ones, as they burn more steadily in the arc lamp.It lhas been hitherto supposed that the violet and blue rays are of almost equal bactericidal power to the ultra-violet rays, but this does not appear to be the case, as is shown both
Occupational Bladder Cancer in a 4,4′-Methylenebis(2-chloroaniline) (MBOCA)-Exposed Worker
Authors: Chiu-Shong Liu, Saou-Hsing Liou, Ching-Hui Loh, Yi-Chun Yu, Shi-Nian Uang, Tung-Sheng Shih, Hong-I Chen
Journal: Environmental Health Perspectives (2005)

A 52-year-old male chemical worker was admitted to the hospital with a history of paroxysmal microscopic hematuria for about 2 years and nocturia with gross hematuria about five times per night for 2 months. He was a nonsmoker and denied a history of any other bladder carcinogen exposure except for occasional pesticide application during agricultural work. Intravenous urogram imaging showed a mass occupying half of the bladder capacity. Cystoscopy revealed a mass over the left dome of the bladder. Cystoscopic biopsy revealed a grade 3 invasive transitional cell carcinoma with marked necrosis. From 1987 until hospital admission in 2001, the patient had worked in a company that produced the 4,4′-methylenebis(2-chloroaniline) (MBOCA) curing agent. He did not wear any personal protective equipment during work. Ambient air MBOCA levels in the purification process area (0.23–0.41 mg/m3) exceeded the U.S. Occupational Safety and Health Administration's permissible exposure level. Urinary MBOCA levels (267.9–15701.1 μg/g creatinine) far exceeded the California Occupational Safety and Health Administration's reference value of 100 μg/L. This patient worked in the purification process with occupational exposure to MBOCA for 14 years. According to the environmental and biologic monitoring data and latency period, and excluding other potential bladder carcinogen exposure, this worker was diagnosed as having occupational bladder cancer due to high exposure to MBOCA through inhalation or dermal absorption in the purification area. This case finding supports that MBOCA is a potential human carcinogen. Safe use of skin-protective equipment and respirators is required to prevent workers from MBOCA exposure.