tbuckley/cabot-search huggingface dataset:
Regulation of acetylcholine receptor gene expression in human myasthenia gravis muscles. Evidences for a compensatory mechanism triggered by receptor loss.
Authors: T Guyon, A Wakkach, S Poea, V Mouly, I Klingel-Schmitt, P Levasseur, D Beeson, O Asher, S Tzartos, S Berrih-Aknin
Journal: Journal of Clinical Investigation (1998)

Myasthenia gravis (MG) is a neuromuscular disorder mediated by antibodies directed against the acetylcholine receptor (nAChR) resulting in a functional nAChR loss. To analyze the molecular mechanisms involved at the muscular target site, we studied the expression of nAChR subunits in muscle biopsy specimens from MG patients. By using quantitative PCR with an internal standard for each subunit, we found that the levels of beta-, delta-, and epsilon-subunit mRNA coding for the adult nAChR were increased in severely affected MG patients, matching our previous data on the alpha-subunit. Messenger levels were highly variable in MG patients but not in controls, pointing to individual factors involved in the regulation of nAChR genes. The fetal subunit (gamma-chain) transcripts were almost undetectable in the extrajunctional region of MG muscle, suggesting that gene regulation in MG differs from that in the denervation model, in which nAChR gamma-subunit mRNA is reexpressed. Nicotinic AChR loss mediated by monoclonal anti-nAChR antibodies in both the TE671 muscle cell line and cultured normal human myotubes induces a similar increase in beta- alphand delta-subunit mRNA levels, suggesting the existence of a new muscular signaling pathway system coupled to nAChR internalization and independent of muscle electrical activity. These data demonstrate the existence of a compensatory mechanism regulating the expression of the genes coding for the adult nAChR in patients with MG.
Two-Year Survival and Mental and Psychomotor Outcomes After the Norwood Procedure
Authors: Joseph Atallah, Irina A. Dinu, Ari R. Joffe, Charlene M.T. Robertson, Reg S. Sauve, John D. Dyck, David B. Ross, Ivan M. Rebeyka
Journal: Circulation (2008)

The Norwood procedure for stage 1 palliation of hypoplastic left heart syndrome is performed with either the modified Blalock-Taussig (MBTS) or the right ventricle-to-pulmonary artery (RVPA) shunt. In our institution, surgical practice changed from use of the MBTS to use of the RVPA shunt in 2002. We analyzed survival and mental and psychomotor outcomes of the 2 consecutive surgical eras.Between September 1996 and July 2005, 94 neonates with hypoplastic left heart syndrome underwent the Norwood procedure. Patients were recruited as neonates and followed up prospectively. Health, mental, and psychomotor outcomes (Bayley Scales of Infant Development-II) were assessed at 2 years. The study subjects were from the Norwood-MBTS era (n=62; 1996 to 2002) or the Norwood-RVPA era (n=32; 2002 to 2005). In the MBTS era, early and 2-year mortality rates were 23% (14/62) and 52% (32/62); the mean (SD) mental and psychomotor developmental indices were 79 (18) and 67 (19). In the RVPA era, early and 2-year mortality rates were 6% (2/32) and 19% (6/32); the mean (SD) mental and psychomotor developmental indices were 85 (18) and 78 (18). The 2-year mortality rate (P=0.002) and the psychomotor developmental index (P=0.029) were improved in the more recent surgical era. On multivariable Cox regression analysis, postoperative highest serum lactate independently predicted 2-year mortality in the MBTS and RVPA eras.Analysis of 2 consecutive surgical eras of hypoplastic left heart syndrome patients undergoing the Norwood procedure showed a significant improvement in 2-year survival and psychomotor development in the more recent era. Adverse neurodevelopmental outcome in this patient population remains a concern.
THE HEART MUSCLE IN PNEUMONIA
Authors: L. H. Newburgh, W. T. Porter
Journal: The Journal of Experimental Medicine (1915)

1. The heart muscle is not functionally impaired in pneumonia, since the pneumonic ventricle beats normally as soon as its food is normal. 2. Pneumonic blood, suddenly fed to normal heart muscle, lowers its efficiency, lessening the duration and the area of contraction. 3. The heart muscle in pneumonia, exposed gradually to the action of the poison, largely adjusts itself to its poisoned food.
Secondary prevention clinics for coronary heart disease: four year follow up of a randomised controlled trial in primary care
Authors: P. Murchie
Journal: BMJ (2003)

To evaluate the effects of nurse led clinics in primary care on secondary prevention, total mortality, and coronary event rates after four years.Follow up of a randomised controlled trial by postal questionnaires and review of case notes and national datasets.Stratified, random sample of 19 general practices in north east Scotland.1343 patients (673 intervention and 670 control) under 80 years with a working diagnosis of coronary heart disease but without terminal illness or dementia and not housebound.Nurse led secondary prevention clinics promoted medical and lifestyle components of secondary prevention and offered regular follow up for one year.Components of secondary prevention (aspirin, blood pressure management, lipid management, healthy diet, exercise, non-smoking), total mortality, and coronary events (non-fatal myocardial infarctions and coronary deaths).Mean follow up was at 4.7 years. Significant improvements were shown in the intervention group in all components of secondary prevention except smoking at one year, and these were sustained after four years except for exercise. The control group, most of whom attended clinics after the initial year, caught up before final follow up, and differences between groups were no longer significant. At 4.7 years, 100 patients in the intervention group and 128 in the control group had died: cumulative death rates were 14.5% and 18.9%, respectively (P=0.038). 100 coronary events occurred in the intervention group and 125 in the control group: cumulative event rates were 14.2% and 18.2%, respectively (P=0.052). Adjusting for age, sex, general practice, and baseline secondary prevention, proportional hazard ratios were 0.75 for all deaths (95% confidence intervals 0.58 to 0.98; P=0.036) and 0.76 for coronary events (0.58 to 1.00; P=0.049) CONCLUSIONS: Nurse led secondary prevention improved medical and lifestyle components of secondary prevention and this seemed to lead to significantly fewer total deaths and probably fewer coronary events. Secondary prevention clinics should be started sooner rather than later.
Knowledge and experience of young people regarding drug misuse, 1969-94
Authors: J D. Wright, L. Pearl
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To monitor young people9s knowledge and experience of illicit drugs between 1969 and 1994 at intervals of five years. <b>Design</b>: The same anonymously completed questionnaire was used throughout. <b>Setting</b>: Three Wolverhampton secondary schools representing three different socioeconomic groups. <b>Subjects</b>: 392 pupils aged 14 to 15 completed the questionnaire in 1994. Previous sample sizes were 471 in 1969, 523 in 1974, 648 in 1979, 540 in 1984, and 380 in 1989. <b>Main outcome measures</b>: Self reported levels of knowledge and experience of illicit drugs. <b>Results</b>: Over 25 years the proportion of pupils who knew someone taking drugs more than quadrupled from 15% (71/471) to 65% (254/392), and the proportion who had been offered drugs increased ninefold from 5% (24) to 45% (175). Both of these proportions more than doubled over the past five years. In 1994 the proportions of pupils mentioning "ecstasy" (methylenedioxymethamphetamine), amphetamines, and crack cocaine increased significantly (P&lt;0.01) and the proportion mentioning opiates decreased significantly (P&lt;0.01). "Poppers" (amyl nitrite) were mentioned for the first time. "To feel big, to show off, look grown up" has continued to be the main perceived reason for taking drugs. Television has continued to be the main source of information. <b>Conclusions</b>: In the past five years in particular young people9s exposure to illicit drugs has increased dramatically. Despite more education about drugs, pupils9 knowledge remains limited. Social pressures remain the first perceived reason for taking drugs. The media have a responsibility not to glamorise drugs. <h3>Key messages</h3> Key messages Despite increased education about drugs in schools young people9s knowledge of the effects and methods of taking illicit drugs remains limited With television continuing to be the main source of information about drugs, producers must give responsible coverage and avoid glamorising the subject Education must take into account both the perceived importance of peer group pressure and young people9s desire for the pleasurable effects of drugs A pragmatic approach to education about drugs that combines primary and secondary prevention strategies should be part of the programme of personal, health, and social education in all secondary schools. An appropriate programme should also be part of the curriculum of primaryschools
Sporotrichosis in Children
Authors: Bernhoff A. Dahl, Peter M. Silberfarb, George A. Sarosi, Robert J. Weeks, Fred E. Tosh
Journal: JAMA (1971)

Nine cases of lymphocutaneous sporotrichosis in children occurred in Kansas in the fall of 1969. All the children had played in stacks of baled prairie hay from which Sporotrichum schenckii was recovered. This outbreak is, to our knowledge, the largest reported outbreak of sporotrichosis in children and the first outbreak reported due to contaminated prairie hay. It is suggested that when adequately exposed to contaminated material children are as susceptible as adults.
Burkitt's Lymphoma — The Message from Microarrays
Authors: Nancy Lee Harris, Sandra J. Horning
Journal: New England Journal of Medicine (2006)

Two articles in this issue of the Journal, by Dave et al.1 and Hummel et al.,2 report on the use of gene-expression microarray technology to improve the accuracy of the diagnosis of Burkitt's lymphoma. The two studies differ in many important ways, but both reach the same conclusion: the gene-expression profiling of cases classified as Burkitt's lymphoma by expert pathologists identifies a characteristic genetic signature that clearly distinguishes this tumor from cases of diffuse large-B-cell lymphoma. Furthermore, the microarray method seems to outperform the expert pathologists: 17 percent1 and 34 percent2 of cases with the gene-expression signature of Burkitt's lymphoma . . .
Abstract 702: Chinese Medicine formulation LQ inhibits FUCCI-expressing HeLa cells at the G0/G1 phase in 2D and 3D culture and invasion with Gelfoam® 3D culture.
Authors: Lei Zhang, Chengyu Wu, Shuya Yano, Robert M. Hoffman
Journal: Cancer Research (2013)

Abstract Traditional Chinese Medicine formula LQ has previously demonstrated anti-tumor and anti-metastasis efficacy. Here, we used fluorescence ubiquitination-based cell cycle indicator (FUCCI) to monitor cell cycle arrest after LQ treatment. FUCCI-HeLa cells were cultured in two dimensional (2D) monolayer, 3D Matrigel®, and 3D Gelform®. Changes of cell cycle status after 24 hours LQ treatment (90mg/ml) were observed using the Olympus FV1000 confocal imaging system. Paclitaxel (Taxol) was used as the positive control which induced a G2/M block of cell cycle. LQ blocked FUCCI-HeLa cells in the G0/G1 phase of the cell cycle in all cultures. In monolayer culture, the control had approximately 45% of the cells in G2/M phase. In contrast, the LQ-treated cells were mostly in the G0/G1 phase (&amp;gt;90%). In 3D dimensional culture (Matrigel®), cancer cells formed spheres. The colonies in control group had 40% of the cells in G2/M phase, but only 15% in LQ-treated culture. The cancer cells at the surface of the sphere were mostly in G2/M phase, and the cancer cells in the center of colonies were in G0/G1 phase. In 3D Gelform® culture, cells grew along the structures of the Gelform®. The control culture had approximately 45% of cells in G2/M phase. In contrast, the cells in LQ-treated culture were mostly in G0/G1 phase (&amp;gt;80%). The cells in control group migrated to 250∼300 μm deep in the Gelfoam®, but only 150∼200 μm deep in LQ-treated culture. FUCCI-HeLa cells in different culture systems demonstrated the efficacy of LQ on the cell cycle and migration. Citation Format: Lei Zhang, Chengyu Wu, Shuya Yano, Robert M. Hoffman. Chinese Medicine formulation LQ inhibits FUCCI-expressing HeLa cells at the G0/G1 phase in 2D and 3D culture and invasion with Gelfoam® 3D culture. [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 702. doi:10.1158/1538-7445.AM2013-702
ANTIBODY AND AGGLUTININ IN PNEUMOCOCCUS PNEUMONIA
Authors: Frederick T. Lord, George E. Nesche
Journal: The Journal of Experimental Medicine (1929)

1. Protective substances and agglutinins were not demonstrated in the blood of patients with pneumonia untreated with serum before the fall in the temperature by crisis or lysis. 2. Protective substances and agglutinins were frequently demonstrated in serum treated patients during the course of the disease. 3. Protective substances and agglutinins were usually present at the time of the temperature fall in patients untreated with serum and persisted for days or weeks thereafter. 4. Protective substances have an important bearing on the outcome. A large proportion of those with protection recover and a large proportion without it die. 5. Agglutinin and antibody may appear simultaneously or one may precede or be present without the other. 6. Tests for agglutinin are unreliable as a control of dosage of specific serum.
Multiphasic Screening for Preschool Children
Authors: Hamilton B. Brown
Journal: JAMA (1972)

Two pediatric screening clinics staffed by students and community volunteers were conducted in low-income, Spanish-American neighborhoods in Albuquerque, NM. The program was designed to examine preschool children by means of history, physical examination, hematocrit, urinalysis, and psychological tests. Three hundred and fifty-two children were examined. Abnormalities in the results of laboratory tests or physical examination were identified in 59 (17%). Information on the results of further evaluation of suspected abnormalities is incomplete but suggests that approximately 5% of the children had chronic physical impairment and that 7% had significant emotional or mental impairment.
Direct In Vivo Observation of Subendocardial Arteriolar Response During Reactive Hyperemia
Authors: Toyotaka Yada, Osamu Hiramatsu, Akihiro Kimura, Hiroyuki Tachibana, Yoko Chiba, Songfang Lu, Masami Goto, Yasuo Ogasawara, Katsuhiko Tsujioka, Fumihiko Kajiya
Journal: Circulation Research (1995)

Abstract To study the vasodilatory capacity of subendocardial (ENDO) arterioles, we evaluated the reactive hyperemic responses of ENDO as well as subepicardial (EPI) arterioles in 40 dogs by our needle-probe intravital microscope. We also examined the individual and combined effects of an ATP-sensitive K + channel blocker (glibenclamide, 200 μg/kg), an inhibitor of nitric oxide synthase ( N G -monomethyl- l -arginine [L-NMMA], 2 μmol/min, 20 minutes), and an adenosine-receptor antagonist (8-phenyltheophylline [8PT], 0.75 μmol/min, 15 minutes). The percent increase in end-diastolic diameter of ENDO arterioles was larger ( P &lt;.01) than that of EPI arterioles during reactive hyperemia, especially for the arterioles larger than 120 μm ( P &lt;.01). The diastolic-to-systolic vascular pulsation amplitude at the peak flow was greater in ENDO than EPI arterioles (25% versus 6%, P &lt;.05). Compared with control conditions, the presence of both glibenclamide and L-NMMA suppressed the vasodilation responses of ENDO arterioles ( P &lt;.01 for both) and EPI arterioles ( P &lt;.05 for both). The effect of L-NMMA was greater in ENDO arterioles ( P &lt;.01), but that of glibenclamide was not different between ENDO and EPI arterioles. 8PT influenced the hyperemic response, although statistical significance was found only in the flow response. The effect of combined infusion of L-NMMA and glibenclamide with or without 8PT was greater than that of individual infusions in both ENDO and EPI arterioles. Conclusions are as follows: (1) The vasodilatory response of ENDO arterioles was even larger than that of EPI arterioles. Thus, the smaller flow reserve of ENDO arterioles may be caused by other factors, including the greater effects of myocardial compression and nitric oxide on the ENDO arterioles. (2) The vascular responses of ENDO and EPI arterioles were modulated by both endothelium-independent and -dependent vasodilative factors, and the effect of each factor including adenosine was associated with the effects of others.
Abstract 3291: Upregulation of Insulin Receptor Substrate-2 (IRS-2) expression by hypoxia
Authors: Katerina Mardilovich, Leslie M. Shaw
Journal: Cancer Research (2010)

Abstract Insulin Receptor Substrate-2 (IRS-2) belongs to the IRS family of cytoplasmic adaptor proteins that mediate signaling from cell surface receptors, including growth factor, cytokine and integrin receptors. Many of these receptors have been implicated in cancer. Although the IRS proteins are highly homologous in structure and have some complementary functions, growing evidence supports that the IRS proteins have unique roles in cancer. IRS-1 has been shown to promote tumor cell proliferation, while IRS-2 has been positively associated with tumor cell motility and invasion. Previously, our lab demonstrated that Polyoma Middle T-derived Irs-2−/− mouse mammary tumors are significantly less metastatic, and Irs-1−/− tumors significantly more metastatic, than their wild-type counterparts. In recent studies, we observed that IRS-2 expression increases in response to hypoxia in both metastatic mouse mammary tumor cells and poorly differentiated ER-negative metastatic human breast carcinoma cells. In contrast, IRS-1 expression does not increase in response to hypoxia, supporting the notion of their non-overlapping functions. Hypoxia promotes the adaptation and resistance of cancer cells to chemo- and radiation therapy, and also promotes tumor cell survival, invasion and metastasis by selecting for aggressive tumor cells that can survive under stressful low oxygen conditions. We have also shown that IRS-2 upregulation in response to hypoxia promotes tumor cell viability and invasion, selecting for tumor cells with increased metastatic potential. To understand how IRS-2 is regulated by hypoxia, we identified a minimal 200 bp region of the IRS-2 promoter located 700 bp upstream from the translation start site that is hypoxia-responsive. Mutation of an E-box binding site within this region that has been previously implicated in regulating IRS-2 in response to hormone stimulation inhibits hypoxic upregulation of IRS-2. We are currently investigating the factors that bind to this E-box to regulate IRS-2 expression. In addition, we have established that HIF is required for IRS-2 upregulation in hypoxic environments, and we are investigating if HIF acts in a direct or indirect manner to regulate IRS-2 expression. Identifying the mechanism by which IRS-2 expression is regulated by hypoxia is essential for developing novel methods to inhibit IRS-2 expression to suppress metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3291.
Sympathetic modulation of hypoxic pulmonary vasoconstriction in intact dogs
Authors: S Brimioulle
Journal: Cardiovascular Research (1997)

Background: The effects of the sympathetic nervous system on hypoxic pulmonary vasoconstriction (HPV) have been reported variably. We studied the effects of adrenergic receptor blockade and epidural blockade on HPV in 32 pentobarbital-anaesthetised intact dogs. Methods: Pulmonary arterial flow–pressure relationships were determined in hyperoxia and hypoxia, at baseline and after α-blockade (phentolamine 2 mg/kg + 50 μg·kg−1·h−1), β-blockade (propranolol 2 mg/kg), αβ-blockade, epidural blockade (lignocaine 20 mg/kg), and αβ- plus epidural blockade. Results: At reference flow of 3.5 l·min−1·m−2, the mean hypoxic response (hypoxia-induced increase in transpulmonary pressure gradient, each n=8) changed from 6.0±0.9 to 3.5±1.0 mmHg after α-blockade, from 5.8±0.9 to 7.3±0.7 mmHg after β-blockade, from 4.1±0.8 to 9.0±1.4 mmHg after αβ-blockade, and from 3.4±1.0 to 4.3±0.9 mmHg after epidural blockade (all P<0.05), and was not affected by epidural blockade after αβ-blockade. Conclusions: In pentobarbital-anaesthetised dogs, (1) HPV is attenuated by α- and enhanced by β-, αβ- and epidural blockade, and (2) epidural blockade has no significant adrenergic-unrelated effect on the pulmonary vasculature.
Treatment of Pulmonary Embolic Disease
Authors: Duncan P. Thomas
Journal: New England Journal of Medicine (1965)

THE evidence continues to accumulate that pulmonary embolic disease represents a major cause of death, especially among patients in hospitals. Smith, Dexter and Dammin,1 in autopsy studies at the Peter Bent Brigham Hospital, Boston, found pulmonary embolism to be the single most common cause of death. Freiman2 found evidence of old or recent pulmonary emboli in 64 per cent of a group of consecutive patients autopsied at the Beth Israel Hospital, Boston. Morrell, Truelove and Barr,3 impressed by an apparent fivefold increase in the number of patients given the diagnosis of pulmonary emboli at the United Oxford Hospitals in the . . .
Intestinal free trypsin concentrations fall only transiently when rats are fed raw soya flour.
Authors: R G Morgan
Journal: Gut (1987)

Raw soya flour (RSF) is thought to cause pancreatic hypertrophy in rats because trypsin inhibitor in the flour binds trypsin in the gut lumen and this lowering of free trypsin concentrations leads to the release of cholecystokinin (CCK). Intestinal enzyme concentrations were therefore studied in rats fed RSF for from one hour to 400 days to determine whether free trypsin concentrations were depressed during the period of pancreatic growth (up to six to eight weeks after starting RSF). Intestinal levels of enzymes were raised from one hour after starting the diet up to 400 days, indicating that stimulation of pancreatic secretion continued for as long as this diet was fed. Free trypsin concentrations were, however depressed only for the first 12 hours. It seems unlikely, therefore, that lowered free trypsin concentrations alone stimulate the release of CCK in these animals.
Relative incidence of agranulocytosis and aplastic anemia
Authors: David W. Kaufman, Judith P. Kelly, Surapol Issaragrisil, Joan‐Ramon Laporte, Theresa Anderson, Micha Levy, Samuel Shapiro, Neal S. Young
Journal: American Journal of Hematology (2005)

Agranulocytosis and aplastic anemia are both rare, life-threatening blood dyscrasias. Agranulocytosis is mainly caused by medicines, whereas the etiology of aplastic anemia is largely unexplained. In two epidemiologic studies using the same methods, we observed a striking inverse relationship between the incidence of the two diseases in different regions, including five countries in Europe, and Israel and Thailand. The annual incidence of agranulocytosis ranged from 1.1 to 4.9 cases per million, and that of aplastic anemia, from 0.7 to 4.1 per million; the inverse correlation was consistent among the regions (R2 = 0.74). There is no clear explanation for this previously unreported pattern, but it seems unlikely to be due to methodology.