tbuckley/cabot-search huggingface dataset:
Possible diagnostic role of telomerase activity evaluation in the differential diagnosis between Spitz naevi and cutaneous malignant melanoma
Authors: P. Tosi, C. Miracco, R. Santopietro, L. Pacenti, R. Perotti, M. Materno, P. Luzi
Journal: British Journal of Dermatology (2000)

Journal Article Possible diagnostic role of telomerase activity evaluation in the differential diagnosis between Spitz naevi and cutaneous malignant melanoma Get access P. Tosi, P. Tosi Institute of Pathological Anatomy and Histology (Istituto di Anatomia e Istologia Patologica) and *Institute of Dermatological Science, Università di Siena, Via delle Scotte 6, 53100 Siena, Italy. Correspondence: Clelia Miracco. E‐mail: miracco@unisi.it Search for other works by this author on: Oxford Academic Google Scholar C. Miracco, C. Miracco Institute of Pathological Anatomy and Histology (Istituto di Anatomia e Istologia Patologica) and *Institute of Dermatological Science, Università di Siena, Via delle Scotte 6, 53100 Siena, Italy. Correspondence: Clelia Miracco. E‐mail: miracco@unisi.it Search for other works by this author on: Oxford Academic Google Scholar R. Santopietro, R. Santopietro Institute of Pathological Anatomy and Histology (Istituto di Anatomia e Istologia Patologica) and *Institute of Dermatological Science, Università di Siena, Via delle Scotte 6, 53100 Siena, Italy. Correspondence: Clelia Miracco. E‐mail: miracco@unisi.it Search for other works by this author on: Oxford Academic Google Scholar L. Pacenti, L. Pacenti Institute of Pathological Anatomy and Histology (Istituto di Anatomia e Istologia Patologica) and *Institute of Dermatological Science, Università di Siena, Via delle Scotte 6, 53100 Siena, Italy. Correspondence: Clelia Miracco. E‐mail: miracco@unisi.it Search for other works by this author on: Oxford Academic Google Scholar R. Perotti, R. Perotti Institute of Pathological Anatomy and Histology (Istituto di Anatomia e Istologia Patologica) and *Institute of Dermatological Science, Università di Siena, Via delle Scotte 6, 53100 Siena, Italy. Correspondence: Clelia Miracco. E‐mail: miracco@unisi.it Search for other works by this author on: Oxford Academic Google Scholar M. Materno, M. Materno Institute of Pathological Anatomy and Histology (Istituto di Anatomia e Istologia Patologica) and *Institute of Dermatological Science, Università di Siena, Via delle Scotte 6, 53100 Siena, Italy. Correspondence: Clelia Miracco. E‐mail: miracco@unisi.it Search for other works by this author on: Oxford Academic Google Scholar P. Luzi P. Luzi Institute of Pathological Anatomy and Histology (Istituto di Anatomia e Istologia Patologica) and *Institute of Dermatological Science, Università di Siena, Via delle Scotte 6, 53100 Siena, Italy. Correspondence: Clelia Miracco. E‐mail: miracco@unisi.it Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 5, 1 May 2000, Pages 1060–1061, https://doi.org/10.1046/j.1365-2133.2000.03506.x Published: 01 May 2000
Metabolic Studies on Hypertensive Patients with Suppressed Plasma Renin Activity Not Due to Hyperaldosteronism
Authors: OSCAR M. HELMER, WALTER E. JUDSON
Journal: Circulation (1968)

Metabolic data obtained during sodium depletion (10-mEq Na, 90-mEq K diet plus thiazide) from 13 hypertensive patients (HT) with low plasma renin activity (PRA) were compared with data from 15 normotensive subjects and three patients with renovascular hypertension (RHT). With Na depletion plasma renin activity and urinary aldosterone excretion increased promptly in NT and RHT. In contrast, PRA in HT after 5 days of Na depletion was only one third that of the NT after 2 days of depletion, and aldosterone excretion did not change significantly. This depressed renin and aldosterone response in HT can be overcome by extending the depletion period and administering spironolactone. In HT, Na and loss of weight was significantly lower than in NT. HT Negroes retained more potassium than HT whites and four out of seven NT Negroes and none of eight NT white subjects had a positive K balance. The hypertension of patients with low PRA appears to be due to genetic or environmental factors or to both.
Comparison of the histopathological effects of two electrosurgical currents in an in vivo porcine model of esophageal endoscopic mucosal resection
Authors: Farzan Bahin, Nicholas Burgess, Sharir Kabir, Hema Mahajan, Duncan McLeod, Vishnu Subramanian, Maria Pellise, Rebecca Sonson, Michael Bourke
Journal: Endoscopy (2015)

Stricture formation is the main limitation of endoscopic resection in the esophagus. The optimal electrosurgical current (ESC) for endoscopic resection in the esophagus and other gastrointestinal sites is unknown. There may be a relationship between the type of ESC used and the development of post-procedure esophageal stricture. Unlike the low power coagulating current (LPCC), the microprocessor-controlled current (MCC), which alternates between short pulse cutting and coagulation, avoids high peak voltages that are thought to result in deep thermal injury. The aim of this study was to determine the histopathological variables associated with these two commonly employed ESCs used for esophageal endoscopic resection.Standardized endoscopic resection of normal mucosa by band mucosectomy was performed by a single endoscopist in 12 adult pigs. The procedures were randomized 1 : 1 to either LPCC (ERBE 100 C at 25 W) or MCC (ERBE Endocut Q, Effect 3). Necropsy and esophagectomy were performed at 72 hours after the procedure. Two histopathologists, who were blinded to the ESC allocation, independently assessed the presence and depth of ulceration, necrosis and inflammation.A total of 45 resections were analyzed. In the LPCC and MCC groups, ulceration extending into the muscularis propria was present in 9/24 (37.5 %) and 1/21 (4.8 %) resected specimens, respectively (P = 0.04). Necrosis extending into the muscularis propria was present in 13/24 (54.1 %) and 1/21 (4.8 %) resected specimens, respectively (P = 0.002). One case of microperforation with muscularis propria injury was noted in the LPCC group compared with none in the MCC group. The quantified mean depth of ulceration, necrosis, and acute inflammation was significantly greater in the LPCC group. In an in vivo porcine survival model of esophageal endoscopic mucosal resection, the use of MCC resulted in significantly less deep thermal ulceration, necrosis, and acute inflammation compared with LPCC. MCC should be used in preference over LPCC for esophageal endoscopic resection.
A novel four base-pair deletion within the A?-GLOBin gene promoter associated with slight increase of A? expression in adult
Authors: Xiao-Dong Huang, Xuexian O. Yang, Rui-Bin Huang, Hong-Yuan Zhang, Hua-Lu Zhao, Yan-Jun Zhao, Cheng-Le Huang, Chun-Jiang Hou, Jun-Wu Zhang
Journal: American Journal of Hematology (2000)

We studied a Chinese family and revealed 5.4% and 3.2% fetal hemoglobin (HbF) with advantageously Agamma type in the mother and the daughter, respectively, using alkali denaturation assay and urea-Triton-acrylamide gel electrophoresis and high-performance liquid chromatography. The father's HbF was less than 0.5%. Large deletion was not observed within the beta-globin gene cluster by restriction endonuclease mapping. Characterization by the polymerase chain reaction (PCR) and DNA sequencing demonstrated the mother is a homozygote with a novel four base-pair "AAGC" (-226 to -223) deletion within the Agamma-globin gene promoter and the daughter is a heterozygote with this deletion. The deletion was not detected in the father. No any mutations were identified in the Ggamma promoter of all the subjects studied. We propose that the small deletion is associated with the slight increase of Agamma gene expression in adult.
GP triage could reduce attendances at emergency departments, study finds
Authors: Z. Kmietowicz
Journal: BMJ (2014)

Getting patients who need urgent out-of-hours care to see a GP or nurse based in or near a hospital could help to reduce emergency department attendances, a report has said.

Monitor, which regulates health services in England, visited health services in Australia, Canada, France, Germany, the Netherlands, Sweden, and the United States to see if the NHS could learn from how these countries delivered core services.1

Overall, the investigation concluded that no other health system offered a way to deliver consistently higher quality …
Tumor necrosis factor induces rapid production of 1'2'diacylglycerol by a phosphatidylcholine-specific phospholipase C.
Authors: S Schütze, D Berkovic, O Tomsing, C Unger, M Krönke
Journal: The Journal of Experimental Medicine (1991)

Tumor necrosis factor (TNF) is a proinflammatory polypeptide that is able to induce a great diversity of cellular responses via modulating the expression of a number of different genes. One major pathway by which TNF receptors communicate signals from the membrane to the cell nucleus involves protein kinase C (PKC). In the present study, we have addressed the molecular mechanism of TNF-induced PKC activation. To this, membrane lipids of the human histiocytic cell line U937 were labeled by incubation with various radioactive precursors, and TNF-induced changes in phospholipid, neutral lipid, and water-soluble metabolites were analyzed by thin layer chromatography. TNF treatment of U937 cells resulted in a rapid and transient increase of 1'2'diacylglycerol (DAG), a well-known activator of PKC. The increase in DAG was detectable as early as 15 s after TNF treatment and peaked at 60 s. DAG increments were most pronounced (approximately 360% of basal levels) when cells were preincubated with [14C]lysophosphatidylcholine, which was predominantly incorporated into the phosphatidylcholine (PC) pool of the plasma-membranes. Further extensive examination of changes in metabolically labeled phospholipids indicated that TNF-stimulated hydrolysis of PC is accompanied by the generation of phosphorylcholine and DAG. These results suggest the operation of a PC-specific phospholipase C. Since no changes in phosphatidic acid (PA) and choline were observed and the production of DAG by TNF could not be blocked by either propranolol or ethanol, a combined activation of phospholipase D and PA-phosphohydrolase in DAG production appears unlikely. TNF-stimulated DAG production as well as PKC activation could be blocked by the phospholipase inhibitor p-bromophenacylbromide (BPB). Since BPB did not inactivate PKC directly, these findings underscore that TNF activates PKC via formation of DAG. TNF stimulation of DAG production could be inhibited by preincubation of cells with a monoclonal anti-TNF receptor (p55-60) antibody, indicating that activation of a PC-specific phospholipase C is a TNF receptor-mediated event.
The Changing Prognosis of Classic Hemophilia (Factor VIII "Deficiency")
Authors: Paul K. Jones, Oscar D. Ratnoff
Journal: Annals of Internal Medicine (1991)

Objective: To estimate relative risk of mortality and median life expectancy for patients with classic hemophilia by a life-table analysis, taking into account deaths that may have occurred in infancy or childhood before the onset of symptoms. Design: Retrospective chart review of clinical series. Setting: Referral-based university medical center. Patients: Seven hundred one patients with classic hemophilia (hemophilia A; factor VIII "deficiency") were studied for the years from 1900 to 1990; patients were identified in 289 families. Measurements and Main Results: Relative risk for mortality and median life expectancy among hemophiliacs were compared with those among normal U.S. males. Overall, mortality (relative to that of contemporaneous U.S. males) was increased about sixfold among severely affected patients, more than twofold among moderately affected patients, and was equivalent to that of U.S. males among mildly affected patients. Median life expectancy at 1 year of age had reached almost 68 years in the decade 1971 to 1980, but declined to only 49 years in the decade 1981 to 1990. Conclusions: After improvement in survival from 1971-1980 (corresponding to widespread treatment with lyophilized concentrates of antihemophilic factor [factor VIII]), relative mortality is now increasing, especially among severely affected patients, in large measure because of the acquired immunodeficiency syndrome (AIDS).
Effect of Chronic Right Atrial Stretch on Atrial Electrical Remodeling in Patients With an Atrial Septal Defect
Authors: Joseph B. Morton, Prashanthan Sanders, Jitendra K. Vohra, Paul B. Sparks, John G. Morgan, Steven J. Spence, Leeanne E. Grigg, Jonathan M. Kalman
Journal: Circulation (2003)

Background— Adults with an atrial septal defect (ASD) frequently develop late atrial arrhythmias. We sought to characterize the pattern and persistence of atrial electrical remodeling caused by chronic right atrial (RA) stretch in this group. Methods and Results— Thirteen ASD patients without atrial arrhythmia (42±10 years old; RA volume, 65±16 mL) and 17 normal control subjects (44±11 years old; RA volume, 38±8 mL) had electrophysiological study to measure (1) atrial effective refractory period (AERP) from the low lateral/high lateral/high septal RA and distal coronary sinus (CS), (2) dispersion of AERP, (3) lateral-RA and CS conduction time during constant pacing, (4) conduction delay across the crista terminalis measuring the number of crista catheter bipoles (0–10) recording discrete double potentials during pacing, (5) corrected sinus node recovery time, and (6) P-wave duration. After ASD closure (8.3±5.6 months), follow-up echo studies (n=12) and electrophysiological study (n=4) were performed. The low-lateral AERP, P-wave duration, sinus node recovery time, and extent of conduction delay across the crista terminalis were significantly greater in ASD patients. No differences were found for other measured electrophysiological study parameters. At follow-up, there was incomplete resolution of RA volume (47±12 mL; P &lt;0.01 versus before surgery), a trend toward shortening of the AERP at the lateral RA and an increase at the distal CS and high septal RA, but persisting extensive, widely split crista double potentials. Conclusions— Chronic RA stretch because of ASD causes electrical remodeling with modest increases in RA ERP, conduction delay at the crista terminalis, and sinus node dysfunction. Conduction delay at the crista terminalis persists beyond ASD closure and may contribute to the long-term atrial arrhythmia substrate in this condition.
Synthesising licensing data to assess drug safety
Authors: Klim McPherson, Elina Hemminki
Journal: BMJ (2004)

Small randomised trials conducted for licensing purposes should record data on adverse results and be made public 

The safety of drugs is important. For full information we need to assess not only the immediate effects but also unexpected longer term effects on serious disease like coronary heart disease or cancer, especially for drugs that will be widely used. Reliably assessing the safety of drugs, however, is fraught with problems such as rare events, long follow up, strong vested interests, and biased reporting. The example of hormone replacement therapy and risk of cardiovascular disease shows some of the problems and presents useful lessons.

Observational studies and trials on intermediate cardiovascular variables indicated that oestrogen and progesterone supplements might protect menopausal women from cardiovascular disease as well as menopausal symptoms. The evidence was convincing. For example, the nurses' study of 120 000 women followed for 30 years estimated the adjusted relative risk for coronary heart disease at 0.47 (95% confidence interval 0.32 0.69) for women currently taking hormone replacement therapy compared with never users.1 This was a common finding in observational studies and understandably led to the strong belief that hormone replacement therapy would be protective. Since the drugs also benefited lipid profiles,2 the argument seemed invincible.

If the results were correct, the risk:benefit ratio of hormone replacement therapy was unambiguously positive.3 Hormone replacement therapy would be beneficial even for asymptomatic women, notwithstanding possible detrimental effects such as an increased risk of breast cancer. These data affected marketing and prescribing; prevention of coronary heart disease became an added indication among symptomatic women, although the licensed indications were for menopausal symptoms and the prevention of osteoporosis.

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Hormone replacement patch: better use should have been made of existing evidence on the risks of HRT

Credit: AJ PHOTO/SPL

The enthusiasm, however, was …

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Weekly Pulse Methotrexate in Rheumatoid Arthritis
Authors: Peter A. Andersen, Sterling G. West, James R. O'dell, Charles S. Via, Robert G. Claypool, Brian L. Kotzin
Journal: Annals of Internal Medicine (1985)

Twelve patients with refractory rheumatoid arthritis were treated with weekly pulse methotrexate in a double-blind, placebo-controlled, crossover study. After 13 weeks of therapy, patients receiving methotrexate showed greater improvement, judged by degree of joint swelling and tenderness, duration of morning stiffness, and subjective assessments of clinical condition, compared to those receiving placebo (p ≤ 0.002). This improvement was associated with a decrease in sedimentation rate and decreases in levels of IgG, IgM, and IgA; no changes were seen in serum rheumatoid factor titer or complement protein levels. Proportions of mononuclear cell subsets that were abnormal before treatment (decreased percentage of total T cells, increased percentage of monocytes) improved toward normal after therapy with methotrexate. However, no changes were seen in elevated pretreatment Leu-3/Leu-2 ratios, in in-vitro proliferative responses of lymphocytes to mitogens, or in immunoglobulin secretory responses to pokeweed mitogen. Weekly pulse methotrexate is effective in the short-term treatment of refractory rheumatoid arthritis. Little evidence for cellular immune suppression was associated with this clinical benefit.
Abstract 1669: DIRAS family members inhibit cell growth and proliferation while inducing autophagy in human ovarian cancer cells.
Authors: Margie N. Sutton, Zhen Lu, Robert C. Bast
Journal: Cancer Research (2013)

Abstract Among the three members of the DIRAS family, DIRAS3 (also known as AplasiaRasHomolog Member I; ARHI) has been best characterized. ARHI is a maternally expressed imprinted tumor suppressor gene that encodes a 26 kDa GTPase with 60% homology to Ras and Rap. ARHI is downregulated in many tumor types including ovarian cancer where its re-expression at physiologic levels inhibits cancer cell growth, reduces motility, induces autophagy and promotes tumor dormancy. ARHI induces autophagy by multiple mechanism including:1) blocking PI3K-Akt signaling and inhibiting mTOR activity, 2) displacing Bcl-2 from Beclin and participating directly in the autophagy initiation complex; and 3) inducing expression of Atg4 and participating directly in the formation of autophagic vesicles, co-localizing with MAP-LC3-II in the vesicle membrane. In human cells, knockdown experiments have demonstrated that ARHI is essential for the induction of autophagy. During evolution, murine cells have lost the ARHI (DIRAS3) gene, yet can still undergo autophagy. Mice and humans express two closely related Ras-related GTPases,DIRAS1 and DIRAS2. These 22 kDa GTPases, have 30-40% overall homology with H-Ras, and 50-60% homology with ARHI (DIRAS3) with the only major difference being the truncation of the N-terminal extension. In this study, we show that transfection of DIRAS1, 2 or 3 with a selectable marker inhibits clonogenic growth of SKOv3 human ovarian cancer cells. Whereas DIRAS3 produced complete inhibition, DIRAS 1 produced 50% inhibition and D IRAS2 35% inhibition of clonogenic growth. One possible mechanism for the growth inhibition observed could be attributed to the induction of autophagy which has been shown by the formation of LC3 punctae in SKOV3 cells and the increased conversion of LC3-I to LC3-II by western blot analysis when DIRAS1 and DIRAS2 were overexpressed by transfection. These findings suggest that these DIRAS family homologs may have similar functions in limiting human tumor progression and in inducing autophagy. Future studies will examine whether DIRAS1 and DIRAS2 serve as surrogates forARHI (DIRAS3) in murine cells. Citation Format: Margie N. Sutton, Zhen Lu, Robert C. Bast. DIRAS family members inhibit cell growth and proliferation while inducing autophagy in human ovarian cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1669. doi:10.1158/1538-7445.AM2013-1669
Occlusion of the Central Retinal Artery in Migraine
Authors: David Krapin
Journal: New England Journal of Medicine (1964)

RETINOVASCULAR phenomena during migraine are not uncommon, but permanent sequelae are rare. These are usually ascribed to some concomitant organic lesion such as aneurysm, tumor, syphilis, cerebrovascular accidents, hypertension, aberrant artery pressure or encephalitis. This paper describes a patient with central-retinal-artery occlusion in migraine, followed for eight years, with no evidence of other complicating abnormality.Case ReportA 28-year-old woman was afflicted with sudden blindness of the left eye.She had a past history of urticaria and angioneurotic edema, with no specific identifiable allergens. In 1948 ophthalmic-type migraine became clinically manifest, characterized by scotoma, left-sided headache and, occasionally, numbness of . . .
IFNγ Enhances Efferocytosis by Macrophages (MΦ) in Chronic Granulomatous Disease (CGD) by a Nitric Oxide (NO) Dependent Mechanism
Authors: D BRATTON, K MCPHILLIPS, A BYRNE, C FRASCH, P HENSON, R FERNANDEZ
Journal: Journal of Allergy and Clinical Immunology (2008)