tbuckley/cabot-search huggingface dataset:
Differences in oxidative response of subpopulations of neutrophils from healthy subjects and patients with rheumatoid arthritis.
Authors: P Eggleton, L Wang, J Penhallow, N Crawford, K A Brown
Journal: Annals of the Rheumatic Diseases (1995)

To determine whether blood neutrophils from healthy individuals and blood and synovial fluid neutrophils from patients with rheumatoid arthritis (RA) responded differently to priming agonists and stimuli of the oxidative burst and, if so, whether this was a property of a subpopulation of neutrophils.Continuous flow electrophoresis was used to separate neutrophils into subpopulations based upon quantitative differences in net negative surface charge. The generation of superoxide anion (O2-) was used as a measure of oxidative activity using 10(-7) mol/l N-formyl-methionylleucyl-phenylalanine (FMLP) as the stimulating agonist and 10(-8) mol/l platelet activating factor (PAF) as the priming agent.The production of O2- by blood and synovial fluid neutrophils from RA patients in response to FMLP was greater than that observed with control blood neutrophils (p < 0.001). Priming of normal blood neutrophils with PAF increased their FMLP induced oxidative burst (p < 0.001), but PAF treatment had no effect on rheumatoid neutrophils. Neutrophils from synovial fluid of RA patients were less electronegative than paired blood samples and exposure of blood neutrophils to FMLP but not PAF reduced their surface charge. Continuous flow electrophoresis isolated three neutrophil subpopulations: cells of least surface electronegativity were ascribed to pool P1 and cells of greatest surface electro-negativity to P3. Normal blood neutrophils from P3, but not P1, showed increased oxidative activity after PAF priming (twofold increase; p < 0.01), whereas the responsiveness of rheumatoid blood and synovial fluid neutrophils from P1 and P3 was not modified by PAF treatment under the same conditions.It is suggested that most of the circulating neutrophils in RA are already in a state of readiness to generate O2- upon activation by an inflammatory stimulus. This is in contrast to normal blood neutrophils, which have both responsive and non-responsive subpopulations with respect to priming agonists.
Vitamin B_12 Deficiency after Gastric Surgery
Authors: G. Divakara Murthy
Journal: Annals of Internal Medicine (1996)

Letters1 December 1996Vitamin B12 Deficiency after Gastric SurgeryG. Divakara Murthy, MD and Hanumappa Visweswaraiah, MDG. Divakara Murthy, MDStratton Veterans Affairs Medical Center, Albany, NY 12208.Search for more papers by this author and Hanumappa Visweswaraiah, MDStratton Veterans Affairs Medical Center, Albany, NY 12208.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-11-199612010-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The study by Sumner and colleagues [1] confirms such metabolic consequences of gastric surgery as vitamin B12 (cobalamin) and iron malabsorption. We agree with the editorial comment by Dr. Green [2] that achlorhydria and the intestinal blind loop could have caused bacterial overgrowth, resulting in malabsorption of vitamin B12. In addition, some study patients could have been receiving histamine-2-receptor antagonists or been using proton pump inhibitors, which would aggravate malabsorption of vitamin B12[3]. However, Sumner and colleagues did not report which medication patients were receiving. A food (protein-bound) cobalamin-absorption test could have resolved some of the issues ...References1. Sumner AE, Chin MM, Abraham JL, Berry GT, Gracely EJ, Allen RH, et al. Elevated methylmalonic acid and homocysteine levels show high prevalence of vitamin B12 deficiency after gastric surgery. Ann Intern Med. 1996; 124:469-76. Google Scholar2. Green R. Screening for vitamin B12 deficiency: caveat emptor [Editorial]. Ann Intern Med. 1996; 124:509-11. Google Scholar3. Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12). Ann Intern Med. 1994; 120:211-5. Google Scholar4. Colon-Otero G, Menke D, Hook CC. A practical approach to the differential diagnosis and evaluation of the adult patient with macrocytic anemia. Med Clin North Am. 1992; 76:581-97. Google Scholar5. Savage DG, Lindenbaum J, Stabler SP, Allen RH. Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies. Am J Med. 1994; 96:239-46. Google Scholar Author, Article, and Disclosure InformationAffiliations: Stratton Veterans Affairs Medical Center, Albany, NY 12208. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1996Volume 125, Issue 11Page: 937KeywordsCobalaminsDietFolate deficiencyFolic acidFoodInpatientsOutpatientsProton pump inhibitorsSurgeryVitamin B12 deficiency Issue Published: 1 December 1996 CopyrightCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
The Prevalence of Symptomatic, Diabetic Neuropathy in an Insulin-treated Population
Authors: Andrew J M Boulton, Graham Knight, John Drury, John D Ward
Journal: Diabetes Care (1985)

The prevalence of symptomatic sensorimotor polyneuropathy has been determined in a population of 382 insulin-treated diabetic subjects aged 15–59 yr. Forty-one subjects (10.7%) were found to have diabetic neuropathy, according to strict diagnostic criteria that required the presence of symptoms and signs of nerve dysfunction in the absence of peripheral vascular disease. There was a significant correlation between glycosylated hemoglobin levels and motor conduction velocity in the median and peroneal nerves in all subjects. This finding further emphasizes the importance of metabolic factors related to hyperglycemia in the impaired nerve function seen in diabetic patients.
Clinical Pharmacology as an Academic Discipline
Authors: Thomas C. Chalmers
Journal: New England Journal of Medicine (1964)

ONE of the natural outgrowths of the professional and legislative furor resulting from the thalidomide incident and the new Food and Drug Administration rules has been an examination of the place of the clinical pharmacologist in medical research and teaching. In the last ten years the number of clinical-pharmacology units in medical schools has increased considerably. At recent medical meetings there has been a great deal of argument among directors of the various units about whether clinical pharmacology should be considered an independent discipline and, if so, whether the emphasis should be primarily on clinical investigation or on pharmacology.Some . . .
Time course of dreaming and sleep organization
Authors: Piero Salzarulo
Journal: Behavioral and Brain Sciences (2000)

The complexity and mysteriousness of mental processes during sleep rule out thinking only in term of generators. How could we know exactly what mental sleep experience (MSE) is produced and when? To refer to REM versus NREM as separate time windows for MSE seems insufficient. We propose that in each cycle NREM and REM interact to allow mentation to reach a certain degree of complexity and consolidation in memory. Each successive cycle within a sleep episode should contribute to these processes with a different weight according to the time of night and distance from sleep onset. This view would avoid assuming too great a separation between REM and NREM functions and attributing psychological functions only to a single state. [Nielsen]
Observations on the systemic effect of topical clobetasol propionate (Dermovate).
Authors: J A Carruthers, P J August, R C Staughton
Journal: BMJ (1975)

Topical application of clobetasol propionate in a strength of 0-05% in cream or ointment (Dermovate) suppressed the hypothalamic-pituitary-adrenal axis in both normal people and patients with diseased skin. In normal people the 9 am serum cortisol level was suppressed when between 45 and 90 g was applied weekly. Insulin stress test results in patients with diseased skin showed an abnormally small response after long-term application of similar amounts. We conclude that long-term administration should be restricted to less than 50 g a week.
Proper Interpretation of Radioisotope Lung Scans
Authors: Joseph A. Orzel
Journal: JAMA (1985)

To the Editor.—  The recent article by Goffman et al 1 was a valuable addition to the literature because it emphasized that perihilar and mediastinal adenopathy can cause significant pulmonary perfusion defects, with relative preservation of ventilation, producing a radionuclide ventilation-perfusion study that could be confused with pulmonary embolic disease. I share their concern that the overdiagnosis of pulmonary emboli may be a common occurrence, perhaps most inappropriately made in young women using oral contraceptives 2 ; however, I am concerned that their experience might discourage the use of radionuclide imaging in evaluating pulmonary embolic disease. The radionuclide study in their patient provided much valuable information, and the diagnostic confusion and inappropriate anticoagulant therapy resulted from improper interpretation of the radionuclide data, not from inherent weakness of this technique.  In our imaging department, the radionuclide ventilation perfusion study of their patient would have been performed after careful review of the chest
Low levels of plasma stem-cell factor in a patient with cyclic neutropenia
Authors: Kenji Shinohara, Kouichi Ariyoshi, Koumei Takeda, Naoko Kameda, Xu Ruirong
Journal: American Journal of Hematology (1997)

nosis, in contrast to RHS associated with peripheral T-cell lymphoma, in which RHS may be a terminal event after a stable course for variable periods [2].In previous studies of a total of 55 Hodgkin's disease patients with marrow involvement, prominent hemophagocytic histocytosis were not described [5,6].Although our patient has stage IV Hodgkin's disease, its focal involvement could not explain the profound pancytopenia.Moreover, a previous study [5] of 36 marrow-positive Hodgkin's disease patients showed most to have normal blood counts.Moreover, in another study of Hodgkin's disease with marrow involvement [6], when combination chemotherapy (MOPP) was given to the patients with initial leukopenia, severe leukopenia occurred, with 42.8% developing life-threatening infections.In our patient, despite the severe initial neutropenia, the leukocyte count actually rose, instead of dropping, during the initial phase of induction chemotherapy (Fig. 2), and our patient tolerated the chemotherapy very well without complications.Although marrow-positive Hodgkin's disease with non-RHS leukopenia was reported to have a poor prognosis due to a low remission rate [6], our patient illustrated that RHS-associated leukopenia in Hodgkin's disease could respond favourably to chemotherapy.
S30 TRUSS is a regulator of TNF -TNF-R1 induced NF- B activation
Authors: I. P. Horan, A. J. Langton, S. Farrow, D. W. Riches, E. R. Chilvers, H. Parfrey
Journal: Thorax (2010)

<h3>Introduction</h3> TNFα is a pleiotropic cytokine that can exert opposing biological actions, either pro-inflammatory or pro-apoptotic, through interaction with its cognate receptor TNF-R1. How this balance is regulated remains to be elucidated. One possible regulator is the novel TNF-R1 interacting protein TRUSS (TNF-R1 ubiquitous signalling and scaffold protein). Ectopic expression of TRUSS activates the transcription factors NF-κB and AP-1. <h3>Aims</h3> To determine the physiological role of TRUSS in TNFα-TNF-R1 signal transduction. <h3>Methods</h3> Human epithelial (A549) cells were transfected with human TRUSS siRNA and responses to TNFα stimulation were assessed by RT-PCR, ELISA, immunoblotting and confocal microscopy. <h3>Results</h3> TRUSS knockdown impaired secretion of the inflammatory chemokines IL-6 and IL-8 following prolonged TNFα stimulation. The maximal reduction of IL-8 mRNA and protein occurred after 12 h of TNFα incubation in the TRUSS deficient cells (p&lt;0.03), whereas the IL-6 responses were decreased after 24 h (p&lt;0.03) (Abstract S30 Figure 1). Furthermore, these effects were abrogated by cycloheximide or the NF-κB inhibitor Bay11-7085, indicating that the inflammatory chemokines were newly synthesised in response to TNFα stimulation via an NF-κB dependent pathway. The upstream signalling molecules TNFR1, TRADD, TRAF2 and RIP were unaffected by TRUSS deficiency. However, phosphorylation of the p50 precursor p105 was augmented in the cytosolic fraction of TRUSS knockdown cells whilst total p50 in the nuclear fraction was reduced by TNFα stimulation. This was associated with impaired nuclear translocation of the activated NF-κB subunit p65 and enhanced JNK phosphorylation. <h3>Conclusions</h3> Our data suggest TRUSS is integral to TNFα-TNF-R1 mediated NF-κB activation. We propose that TRUSS functions as a scaffold protein involved in the proteasomal processing of p105 into the p50 subunit. Inhibition of this process impairs the nuclear translocation of NF-κB and the consequent p65/p50 regulated gene transcription. Hence, TRUSS may be a novel target for modulating the inflammatory functions of TNFα-TNF-R1 signalling.
Smoking Affects Nocturnal Blood Pressure
Authors: A. Artom, D. Mela, F. Orsoni, S. Ricciardi
Journal: JAMA (1991)

<h3>To the Editor.—</h3> The physiological nocturnal decline of the blood pressure in normotensive and hypertensive patients is not observed in autonomic dysfunction (eg, cardiac transplantation and some diabetic patients).<sup>1,2</sup> The lack of the normal nocturnal decrease in blood pressure has also been found in a group of elderly hypertensive patients with cardiovascular damage and was attributed in this case to reduced arterial distensibility.<sup>3</sup> We have shown, by studying a group of young subjects with no other risk factors and no atherosclerotic cardiovascular complications, that smoking affects the nocturnal blood pressure profile. <h3>Study.—</h3> We studied 22 normotensive subjects, heavy smokers for at least 20 years (12 men and 10 women, aged 36 to52 years; mean, 47 years) and 14 normotensive nonsmokers (eight men and six women, aged 38 to 54 years; mean, 50 years) by noninvasive 24-hour blood pressure monitoring, at 15-minute intervals. Blood pressure was assessed using
Identification of <i>SPOCK2</i> As a Susceptibility Gene for Bronchopulmonary Dysplasia
Authors: Alice Hadchouel, Xavier Durrmeyer, Emmanuelle Bouzigon, Roberto Incitti, Johanna Huusko, Pierre-Henri Jarreau, Richard Lenclen, Florence Demenais, Marie-Laure Franco-Montoya, Inès Layouni, Juliana Patkai, Jacques Bourbon, Mikko Hallman, Claude Danan, Christophe Delacourt
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Bronchopulmonary dysplasia is the most common chronic respiratory disease in premature infants. Genetic factors might contribute to bronchopulmonary dysplasia susceptibility.To identify genetic variants involved in bronchopulmonary dysplasia through a genome-wide association study.We prospectively evaluated 418 premature neonates (gestational age <28 wk), of whom 22% developed bronchopulmonary dysplasia. Two discovery series were created, using a DNA pooling strategy in neonates from white and African ancestry. Polymorphisms associated with the disease were confirmed in an independent replication population. Genes were then explored by fine mapping and associations were replicated in an external Finnish population of 213 neonates. Validated genes expression patterns were studied in rat lung, after air or hyperoxia exposure.SPOCK2 gene was identified by both discovery series. The most significant polymorphism (rs1245560; P = 1.66 × 10(-7)) was confirmed by individual genotyping, and in the replication population (P = 0.002). Fine mapping confirmed the association of rs1245560 with bronchopulmonary dysplasia in both white and African populations with adjusted odds ratios of 2.96 (95% confidence interval [CI], 1.37-6.40) and 4.87 (95% CI, 1.88-12.63), respectively. In white neonates, rs1049269 was also associated with the disease (odds ratio, 3.21; 95% CI, 1.51-6.82). These associations were replicated in the Finnish population. In newborn rat lungs, SPOCK2 mRNA levels markedly increased during the alveolar stage of lung development. After rat exposure to hyperoxia, SPOCK2 expression increased relative to air-exposed controls.We identified SPOCK2 as a new possible candidate susceptibility gene for bronchopulmonary dysplasia. Its lung expression pattern points toward a potential role in alveolarization.
Social Responsiveness, an Autism Endophenotype: Genomewide Significant Linkage to Two Regions on Chromosome 8
Authors: Jennifer K. Lowe, Donna M. Werling, John N. Constantino, Rita M. Cantor, Daniel H. Geschwind
Journal: American Journal of Psychiatry (2014)

Objective: Autism spectrum disorder is characterized by deficits in social function and the presence of repetitive and restrictive behaviors. Following a previous test of principle, the authors adopted a quantitative approach to discovering genes contributing to the broader autism phenotype by using social responsiveness as an endophenotype for autism spectrum disorder. Method: Linkage analyses using scores from the Social Responsiveness Scale were performed in 590 families from the Autism Genetic Resource Exchange, a largely multiplex autism spectrum disorder cohort. Regional and genomewide association analyses were performed to search for common variants contributing to social responsiveness. Results: Social Responsiveness Scale scores were unimodally distributed in male offspring from multiplex autism families, in contrast with a bimodal distribution observed in female offspring. In correlated analyses differing by Social Responsiveness Scale respondent, genomewide significant linkage for social responsiveness was identified at chr8p21.3 (multipoint LOD=4.11; teacher/parent scores) and chr8q24.22 (multipoint LOD=4.54; parent-only scores), respectively. Genomewide or linkage-directed association analyses did not detect common variants contributing to social responsiveness. Conclusions: The sex-differential distributions of Social Responsiveness Scale scores in multiplex autism families likely reflect mechanisms contributing to the sex ratio for autism observed in the general population and form a quantitative signature of reduced penetrance of inherited liability to autism spectrum disorder among females. The identification of two strong loci for social responsiveness validates the endophenotype approach for the identification of genetic variants contributing to complex traits such as autism spectrum disorder. While causal mutations have yet to be identified, these findings are consistent with segregation of rare genetic variants influencing social responsiveness and underscore the increasingly recognized role of rare inherited variants in the genetic architecture of autism spectrum disorder.
Simvastatin Normalizes Autonomic Neural Control in Experimental Heart Failure
Authors: Rainer U. Pliquett, Kurtis G. Cornish, Jacob D. Peuler, Irving H. Zucker
Journal: Circulation (2003)

Background— HMG-CoA reductase inhibitors (statins) have been shown to beneficially affect outcomes in chronic heart failure (CHF). We hypothesized that statins exert effects on autonomic function, as assessed by plasma norepinephrine levels, direct recordings of renal sympathetic nerve activity (RSNA), and baroreflex function. Methods and Results— Normolipidemic CHF rabbits were treated with simvastatin or vehicle. CHF was induced by continuous ventricular pacing at 320 to 340 bpm for 3 weeks. Two to 3 days after instrumentation of the rabbits with renal nerve electrodes and arterial and venous catheters, blood samples and RSNA recordings were obtained in the conscious state. Baroreflex function was assessed after administration of sodium nitroprusside and phenylephrine. Mean baseline RSNA (±SEM) in normal rabbits was 19.3±3.8%; in CHF rabbits, 39.4±2.9% ( P &lt;0.05); in CHF rabbits on low-dose (0.3 mg · kg −1 · d −1 ) simvastatin, 39.8±8.3% ( P &lt;0.05); and in CHF rabbits on high-dose simvastatin (3 mg · kg −1 · d −1 ), 21.1±4.5% ( P =NS). Similar data were observed for plasma norepinephrine. In CHF rabbits treated with 3 mg · kg −1 · d −1 simvastatin, baroreflex regulation of heart rate to transient hypotension with sodium nitroprusside was normalized by 66% compared with CHF controls. Conclusions— These are the first data showing that non–lipid-lowering statin effects include a normalization of sympathetic outflow and reflex regulation in CHF. The precise neural and cellular pathways involved in these responses need further clarification. This finding may have important implications for the treatment of CHF and progression of the disease process.
Anaphylaxis after dental treatment with a formaldehyde‐containing tooth‐filling material
Authors: F. Wantke, W. Hemmer, T. Haglmüller, M. Götzu, R. Jarisch
Journal: Allergy (1995)

A 67‐year‐old patient developed systemic reactions after application of a formaldehyde‐containing tooth filling. She had a clearly positive RAST result for formaldehyde, whereas skin prick testing and patch tests were negative. Sensitization to formaldehyde appears to have occurred 1 year previously. Induction of formaldehyde allergy may represent a major complication during dental treatment, and assessment of specific IgE should he considered in patients at risk.