tbuckley/cabot-search huggingface dataset:
Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma
Authors: Gareth R. Howell, Ileana Soto, Xianjun Zhu, Margaret Ryan, Danilo G. Macalinao, Gregory L. Sousa, Lura B. Caddle, Katharine H. MacNicoll, Jessica M. Barbay, Vittorio Porciatti, Michael G. Anderson, Richard S. Smith, Abbot F. Clark, Richard T. Libby, Simon W.M. John
Journal: Journal of Clinical Investigation (2012)

Glaucoma is a common ocular disorder that is a leading cause of blindness worldwide. It is characterized by the dysfunction and loss of retinal ganglion cells (RGCs). Although many studies have implicated various molecules in glaucoma, no mechanism has been shown to be responsible for the earliest detectable damage to RGCs and their axons in the optic nerve. Here, we show that the leukocyte transendothelial migration pathway is activated in the optic nerve head at the earliest stages of disease in an inherited mouse model of glaucoma. This resulted in proinflammatory monocytes entering the optic nerve prior to detectable neuronal damage. A 1-time x-ray treatment prevented monocyte entry and subsequent glaucomatous damage. A single x-ray treatment of an individual eye in young mice provided that eye with long-term protection from glaucoma but had no effect on the contralateral eye. Localized radiation treatment prevented detectable neuronal damage and dysfunction in treated eyes, despite the continued presence of other glaucomatous stresses and signaling pathways. Injection of endothelin-2, a damaging mediator produced by the monocytes, into irradiated eyes, combined with the other glaucomatous stresses, restored neural damage with a topography characteristic of glaucoma. Together, these data support a model of glaucomatous damage involving monocyte entry into the optic nerve.
The pH of Ascitic Fluid in the Diagnosis of Spontaneous Bacterial Peritonitis in Alcoholic Cirrhosis
Authors: Norman Gitlin, John L. Stauffer, Ronald C. Silvestri
Journal: Hepatology (1982)

Fifty-six patients with alcoholic cirrhosis and ascites were studied. The ascitic fluid was analyzed for pH, PO2, PCO2 glucose, protein, specific gravity, amylase, lactic dehydrogenase, white blood cell count, polymorphonuclear count, and cytology. It was also cultured aerobically and anaerobically. Simultaneously, arterial blood was analyzed for pH, PO2, and PCO2. Venous blood was analyzed for complete blood count, protein, aspartate transaminase, and it was also cultured under aerobic and anaerobic conditions. Six patients had spontaneous bacterial peritonitis (SBP), i.e., culture was positive for Escherichia coli in five and Streptococcus faecalis in one. The mean (+/- S.E.) ascitic fluid pH in the SBP group wa 7.25 +/- 0.06 with a range of 7.12 to 7.31, while the ascitic fluid pH in the group with sterile ascites was 7.47 +/- 0.07 with a range of 7.39 to 7.58. The pH of the blood in both groups was 7.47 +/- 0.03. The pH of the ascites in the SBP group was significantly different from the pH in the group with sterile ascites, p less than 0.001. It was also significantly different from the blood pH, p less than 0.001. Highly significant inverse correlations existed between the ascitic pH in the SBP group and the ascitic white blood cell count (r = 0.84, p less than 0.01) and between the ascite pH in the SBP group and the ascitic polymorphonuclear count (r = -0.87 ,p less than 0.01). The ascitic fluid pH is recommended as an easy, quick, sensitive, and specific means of diagnosing SBP and it overcomes the problem of the present SBP diagnostic methods of utilizing an absolute white blood cell count greater than 500 per mm3 or a polymorphonuclear count greater than 250 per mm3 in which false positive interpretations occur.
Electrophysiological findings and long-term follow-up of patients with the permanent form of junctional reciprocating tachycardia treated by catheter ablation.
Authors: W W Chien, T J Cohen, M A Lee, M D Lesh, J C Griffin, N B Schiller, M M Scheinman
Journal: Circulation (1992)

BACKGROUND The permanent form of junctional reciprocating tachycardia (PJRT) commonly presents as recurrent drug-refractory, narrow-complex tachycardia. We studied the efficacy and safety of catheter ablation in treating these patients. METHODS AND RESULTS Six patients with the diagnosis of PJRT were treated at our institution with direct-current catheter ablation. The study cohort comprised three men and three women with a mean age of 33.8 +/- 4.5 years. The mean time from onset of symptoms to ablation was 129 +/- 44.7 months. All failed multiple drug therapy (mean number of drugs failed was 5.3 +/- 0.5). The left ventricular ejection fractions were calculated by echocardiography and were greater than 60% in all except two patients, whose ejection fractions were 25% and 32%. Symptom duration was significantly longer in those with depressed ejection fraction compared with normal patients (258 versus 64.5 months, p less than 0.01). Electrophysiological findings revealed evidence of an atrioventricular reciprocating tachycardia involving retrograde decremental conduction over an accessory pathway localized to the posteroseptal area. Five patients received two direct-current shocks (250 +/- 16.7 J per shock) via paired electrodes from a catheter positioned just outside the coronary sinus os to a patch placed between the scapulae or on the anterior chest wall. One patient received a single direct-current shock of 300 J. The only complication was the development of complete atrioventricular block in one patient. This patient had previously undergone permanent pacemaker insertion for the sick sinus syndrome. The mean hospital stay after ablation was 2.2 days. Mean peak creatinine phosphokinase after ablation was 352 +/- 58.1 units/l and the MB fraction was 12 +/- 2%. Follow-up echocardiograms or gated nuclear studies showed improvement of ejection fraction in the two patients who presented with depressed ejection fractions. After a mean follow-up of 35.8 +/- 10.3 months, all patients remained free of tachycardia without antiarrhythmic drugs. CONCLUSIONS We conclude that catheter ablation by using direct current energy appears to be an effective treatment in patients with PJRT.
Normal hematopoiesis and neurofibromin-deficient myeloproliferative disease require Erk
Authors: Karl Staser, Su-Jung Park, Steven D. Rhodes, Yi Zeng, Yong Zheng He, Matthew A. Shew, Jeffrey R. Gehlhausen, Donna Cerabona, Keshav Menon, Shi Chen, Zejin Sun, Jin Yuan, David A. Ingram, Grzegorz Nalepa, Feng-Chun Yang, D. Wade Clapp
Journal: Journal of Clinical Investigation (2012)

Neurofibromatosis type 1 (NF1) predisposes individuals to the development of juvenile myelomonocytic leukemia (JMML), a fatal myeloproliferative disease (MPD). In genetically engineered murine models, nullizygosity of Nf1, a tumor suppressor gene that encodes a Ras-GTPase–activating protein, results in hyperactivity of Raf/Mek/Erk in hematopoietic stem and progenitor cells (HSPCs). Activated Erk1/2 phosphorylate kinases and transcription factors with myriad mitogenic roles in diverse cell types. However, genetic studies examining Erk1/2's differential and/or combined control of normal and Nf1-deficient myelopoiesis are lacking. Moreover, prior studies relying on chemical Mek/Erk inhibitors have reached conflicting conclusions in normal and Nf1-deficient mice. Here, we show that while single Erk1 or Erk2 disruption did not grossly compromise myelopoiesis, dual Erk1/2 disruption rapidly ablated granulocyte and monocyte production in vivo, diminished progenitor cell number, and prevented HSPC proliferation in vitro. Genetic disruption of Erk1/2 in the context of Nf1 nullizygosity (Mx1Cre+Nf1flox/floxErk1–/–Erk2flox/flox) fully protects against the development of MPD. Collectively, we identified a fundamental requirement for Erk1/2 signaling in normal and Nf1-deficient hematopoiesis, elucidating a critical hematopoietic function for Erk1/2 while genetically validating highly selective Mek/Erk inhibitors in a leukemia that is otherwise resistant to traditional therapy.
Longitudinal Study of Moderate Weight Change and Sleep-Disordered Breathing
Authors: Paul E. Peppard
Journal: JAMA (2000)

ContextExcess body weight is positively associated with sleep-disordered breathing (SDB), a prevalent condition in the US general population. No large study has been conducted of the longitudinal association between SDB and change in weight.ObjectiveTo measure the independent longitudinal association between weight change and change in SDB severity.DesignPopulation-based, prospective cohort study conducted from July 1989 to January 2000.Setting and ParticipantsSix hundred ninety randomly selected employed Wisconsin residents (mean age at baseline, 46 years; 56% male) who were evaluated twice at 4-year intervals for SDB.Main Outcome MeasuresPercentage change in the apnea-hypopnea index (AHI; apnea events + hypopnea events per hour of sleep) and odds of developing moderate-to-severe SDB (defined by an AHI ≥15 events per hour of sleep), with respect to change in weight.ResultsRelative to stable weight, a 10% weight gain predicted an approximate 32% (95% confidence interval [CI], 20%-45%) increase in the AHI. A 10% weight loss predicted a 26% (95% CI, 18%-34%) decrease in the AHI. A 10% increase in weight predicted a 6-fold (95% CI, 2.2-17.0) increase in the odds of developing moderate-to-severe SDB.ConclusionsOur data indicate that clinical and public health programs that result in even modest weight control are likely to be effective in managing SDB and reducing new occurrence of SDB.
Esophageal and Antral Strictures Due to Ingestion of Household Ammonia
Authors: Richard A. Norton
Journal: New England Journal of Medicine (1960)

THE ingestion of household ammonia, either in attempted suicide or by error, has rarely been associated with severe complications. In the fall of 1958, 2 patients were seen at the Grace-New Haven Community Hospital after they had attempted suicide by taking household ammonia (the 15-molar solution of 28 per cent ammonia). The lesions that eventually developed not only were unusually severe but also were different from those previously described, in that combined esophageal and antral strictures developed.A review of the English medical literature of the last twenty years reveals 3 case reports of ammonia burns. The patient of Chassin . . .
RNA Interference Targeting STIM1 Suppresses Vascular Smooth Muscle Cell Proliferation and Neointima Formation in the Rat
Authors: Fleur C Aubart, Yassine Sassi, Alain Coulombe, Nathalie Mougenot, Cédric Vrignaud, Pascal Leprince, Philippe Lechat, Anne-Marie Lompré, Jean-Sébastien Hulot
Journal: Molecular Therapy (2008)

Our objective was to study the expression and function of stromal interaction molecule 1 (STIM1), an endoplasmic reticulum protein recently identified as the calcium sensor that regulated Ca(2+)-released activated channels in T cells. STIM1 was found to be upregulated in serum-induced proliferating human coronary artery smooth muscle cells (hCASMCs) as well as in the neointima of injured rat carotid arteries. Growth factors-induced proliferation was significantly lower in hCASMC transfected with STIM1 siRNA than in those transfected with scrambled siRNA (increase relative to 0.1% S: 116 +/- 12% and 184 +/- 16%, respectively, P < 0.01). To assess the role of STIM1 in preventing vascular smooth muscle cells (VSMCs) proliferation in vivo, we infected balloon-injured rat carotid arteries with an adenoviral vector expressing a short hairpin (sh) RNA against rat STIM1 mRNA (Ad-shSTIM1). Intima/media ratios reflecting the degree of restenosis were significantly lower in Ad-shSTIM1- infected arteries than in Ad-shLuciferase-infected arteries (0.34 +/- 0.02 vs. 0.92 +/- 0.11, P < 0.006). Finally, we demonstrated that silencing STIM1 prevents activation of the transcription factor NFAT (nuclear factor of activated T cell). In conclusion, STIM1 appears as a major regulator of in vitro and in vivo VSMC proliferation, representing a novel and original pharmacological target for prominent vascular proliferative diseases.
The Gold-Headed Cane
Authors: John H. Talbott
Journal: JAMA (1968)

This attractive facsimile edition was prepared in commemoration of the 450th anniversary of the granting in 1518 of the Royal Charter by King Henry VIII to the Royal College of Physicians, London. It was introduced in Boston at a joint convocation of the London College and the 49th Annual Session of the American College of Physicians. Although the author of the original edition published in 1827 as well as the second edition was not identified, the anonymity was not a well-kept secret. Thus it is appropriate that the facsimile copy of The Gold-Headed Cane is supplemented by a colored portrait of Macmichael on the frontispiece and a biographical introduction by Thomas Hunt, MD. A further commendable feature is the interesting and annotated notes by the author on the interleafs. The contents is a description of the practice of physic in London more than two centuries ago as recounted by Radcliffe,
Discovery of Insulin
Authors: H.A. Swart
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Amagrams, of Dec 27, 1971, seemed quite correct until the end of the second paragraph. At that time you said that "With the somewhat grudging acquiescence of the head of the department, Prof J.J.R. Macleod..." From this, one would infer that Prof Macleod was head of the Department of Physiology at the University of Western Ontario. This, of course, was not true. He was Professor of Physiology of the University of Toronto, where work on insulin was done. The story we heard as students was that Dr. Banting went to the authorities at the University of Western Ontario and asked for laboratory space, equipment, and dogs in order to carry out his ideas regarding a pancreatic extract to be used in the treatment of insulin. They turned him down and then he went to Toronto where with six weeks and the assistance of Dr. Charles Best enough
The role of CHOP messenger RNA expression in the link between oxidative stress and apoptosis
Authors: Yasuyo Ariyama, Yoshito Tanaka, Hiroyuki Shimizu, Kenju Shimomura, Shuichi Okada, Tsugumichi Saito, Eijiro Yamada, Seiichi Oyadomari, Masataka Mori, Masatomo Mori
Journal: Metabolism (2008)
PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest
Authors: Jiyong Liang, Judit Zubovitz, Teresa Petrocelli, Rouslan Kotchetkov, Michael K. Connor, Kathy Han, Jin-Hwa Lee, Sandra Ciarallo, Charles Catzavelos, Richard Beniston, Edmee Franssen, Joyce M. Slingerland
Journal: Nature Medicine (2002)
Renal Lesions, Gross Hematuria, and Marrow Granulomas in Infectious Mononucleosis
Authors: Edward A. Taub
Journal: JAMA (1966)

HEMORRHAGIC manifestations of infectious mononucleosis are not uncommon. Virtually every organ system has been involved. 1 Gross hematuria is quite rare, and renal biopsies have not been done in the few cases reported.  Granuloma formation in the bone marrow in infectious mononucleosis is a phenomenon which was first reported less than 20 years ago. 2 This finding, although reported to be quite common, does not yet seem to be within the realm of common medical knowledge.  It will be the purpose of this paper to present and discuss the significance of a case of infectious mononucleosis associated with granulomatous changes in the bone marrow, unique renal lesions, and gross hematuria.  Report of a Case  The patient is a 19-year-old white boy, who had been experiencing confusion, visual hallucinations, chills, fever, sore throat, and grossly bloody urine during the week preceding his hospital admission. The patient was seen by a local
Hemodynamic Mechanisms Responsible for Reduced Subendocardial Coronary Reserve in Dogs With Severe Left Ventricular Hypertrophy
Authors: Luc Hittinger, Israel Mirsky, You-Tang Shen, Thomas A. Patrick, Sanford P. Bishop, Stephen F. Vatner
Journal: Circulation (1995)

Background Reduced subendocardial coronary reserve is a hallmark of left ventricular hypertrophy (LVH). The goal of this study was to determine whether hemodynamic, as opposed to structural, mechanisms were responsible for the reduced subendocardial coronary reserve. Methods and Results The effects of near-maximal vasodilation with adenosine were examined in 10 conscious dogs with LVH (79% increase in ratio of LV weight to body weight) induced by aortic banding in puppies with and without preload reduction. At baseline, LV end-diastolic pressure, LV end-diastolic circumferential and compressive radial wall stresses, and LV myocardial blood flow were similar in dogs with LVH and sham-operated controls, while LV end-systolic circumferential wall stress tended to be greater in the LVH group compared with the control group. In control dogs, adenosine reduced LV circumferential end-systolic and end-diastolic wall stresses and compressive radial subendocardial wall stress; LV subendocardial blood flow increased (from 1.41±0.16 to 3.58±0.27 mL · min −1 · g −1 ) and the ratio of subendocardial to subepicardial blood flow decreased from 1.30±0.07 to 0.69±0.05. In dogs with LVH, during adenosine infusion, LV circumferential end-systolic and end-diastolic wall stresses and LV radial subendocardial wall stresses remained elevated, the increase in LV subendocardial blood flow was significantly smaller (from 1.11±0.11 to 2.27±0.24 mL · min −1 · g −1 , P &lt;.05), and the subendocardial/epicardial ratio fell to a lower level (from 1.22±0.17 to 0.35±0.03, P &lt;.05). When LV wall stresses during adenosine were reduced in a subgroup of 5 dogs with LVH, the endocardium/epicardium ratio during adenosine infusion was no longer different from that in control dogs (0.63±0.11), nor was the level of subendocardial blood flow different (3.42±0.60 mL · min −1 · g −1 ). Conclusions These data suggest that hemodynamic factors, eg, compressive forces, are an important component of the reduced subendocardial coronary reserve as opposed to structural alterations, even in the presence of severe LVH.
Incidental Early Stage Endometrial Adenocarcinoma Diagnosed by F-18 FDG PET-CT, Which Was Negative on Ultrasound and Nonspecific on MRI
Authors: William Makis, Gad Abikhzer, Jerry Stern
Journal: Clinical Nuclear Medicine (2010)

A 65-year-old woman with a history of gastric adenocarcinoma was referred for a follow-up F-18 FDG PET-CT scan. Although there was no evidence of recurrence of her gastric malignancy, there was an incidental finding of mild focal FDG uptake in the mid uterus. This was considered suspicious, especially in a postmenopausal woman, and she was referred for further imaging. Ultrasound did not find any abnormalities, and MRI reported a nonspecific focus of mild endometrial thickening. Extensive histopathological sampling of the endometrium revealed a focus of intramucosal endometrial adenocarcinoma; the patient was diagnosed with Stage IA disease and treated surgically. This case demonstrates the importance of alerting referring physicians to even mildly FDG-avid focal abnormalities of the endometrium of postmenopausal women, despite normal or nonspecific correlative diagnostic imaging results.
Effect of a single dose of salmeterol on the increase in airway eosinophils induced by allergen challenge in asthmatic subjects
Authors: F. L Dente, L. Bancalari, E. Bacci, M. L Bartoli, S. Carnevali, S. Cianchetti, A. Di Franco, D. Giannini, B. Vagaggini, R. Testi, P. L Paggiaro
Journal: Thorax (1999)

<h3>BACKGROUND</h3> The long acting β<sub>2</sub> agonist salmeterol is very effective in preventing asthmatic responses to specific stimuli, and this effect could theoretically be due to some anti-inflammatory property in addition to bronchodilator property. <h3>METHODS</h3> The protective effect of a single dose of salmeterol (50 μg) on allergen induced early and late responses and on the associated airway inflammation was investigated in a double blind, placebo controlled, crossover study in 11 atopic asthmatic subjects. Eosinophil percentages and concentrations of eosinophil cationic protein (ECP) in peripheral blood and in hypertonic saline induced sputum were measured 24 hours after allergen inhalation. <h3>RESULTS</h3> Salmeterol effectively inhibited both early and late asthmatic responses in comparison with placebo. Salmeterol also inhibited the increase in the percentage of eosinophils in the sputum 24 hours after allergen inhalation (median (range) baseline 6% (1–36), after placebo 31% (5–75), after salmeterol 12% (1–63)). However, the increase in both sputum and serum ECP concentrations 24 hours after allergen challenge was not affected by pretreatment with salmeterol. <h3>CONCLUSIONS</h3> A single dose of salmeterol inhibits the allergen induced airway responses and the increase in sputum eosinophils after allergen challenge.
Complete Heart Block with Thyrotoxic Myocarditis
Authors: Albert L. Muggia, Melvin Stjernholm, Ted Houle
Journal: New England Journal of Medicine (1970)

MANY reports have appeared in the literature of uncomplicated hyperthyroidism associated with prolongation of the PR interval and with transient abnormalities of atrioventricular conduction.1 2 3 4 5 The prevalence varies from series to series, but a fair percentage of patients with thyrotoxicosis have been noted to have these abnormalities.We recently saw a case of complete heart block associated with thyrotoxicosis that was then followed by first-degree heart block and then a normal electrocardiogram. This has been reported only on a few occasions. Davis and Smith6 presented six cases of complete heart block in hyperthyroidism after acute infections, and Steuer7 described a 39-year-old . . .
A Comparison of the Framingham Risk Index, Coronary Artery Calcification, and Culprit Plaque Morphology in Sudden Cardiac Death
Authors: Allen J. Taylor, Allen P. Burke, Patrick G. O’Malley, Andrew Farb, Gray T. Malcom, John Smialek, Renu Virmani
Journal: Circulation (2000)

Background —Neither clinical prediction models nor noninvasive imaging tests that detect coronary artery calcification identify all patients who experience acute coronary events. Variations in culprit plaque morphology may account for these inaccuracies. Methods and Results —We compared the 10-year Framingham risk index, histologic coronary calcification, and culprit plaque morphology in 79 consecutive adults with sudden cardiac death. There was a modest relationship between the Framingham risk index and the extent of histologic coronary calcification ( r =0.35, P =0.002). Agreement in risk classification between the histologic calcification score and the Framingham risk index occurred in 50 of 79 cases (63.3%, P =0.039). Either a focus of coronary artery calcification ≥40 μmol/L (62% of cases) or a Framingham risk index score ≥ average risk for age (62% of cases) were present in 66 of 79 (83.5%) cases. Cases with plaque erosion (n=22) had significantly less coronary calcification ( P =0.003) and lower Framingham risk index ( P =0.001) scores than stable (n=27) or ruptured (n=30) plaques. Fourteen of 22 (63.6%) cases of plaque erosion were classified as low risk by both the Framingham risk index and the histologic calcification score. Conclusions —The prediction of sudden cardiac death using the Framingham risk index and the measurement of coronary calcification are distinct methods of assessing risk for sudden cardiac death. Excessive reliance on either method alone will produce errors in risk classification, particularly for patients at risk of plaque erosion, but their combination may be complementary.
The p210BCR-ABL tyrosine kinase of chronic myeloid leukemia causes resistance to radio-induced apoptotic death by inhibiting the proapoptotic BAX gene
Authors: M Mancini, G Brusa, M Benvenuti, L Mazzacurati, F Campanini, E Barbieri, S Cammelli, N Calonghi, G Martinelli, M Baccarani, M A Santucci
Journal: Leukemia (2003)