tbuckley/cabot-search huggingface dataset:
The Pharmacological Chaperone 1-Deoxygalactonojirimycin Reduces Tissue Globotriaosylceramide Levels in a Mouse Model of Fabry Disease
Authors: Richie Khanna, Rebecca Soska, Yi Lun, Jessie Feng, Michelle Frascella, Brandy Young, Nastry Brignol, Lee Pellegrino, Sheela A Sitaraman, Robert J Desnick, Elfrida R Benjamin, David J Lockhart, Kenneth J Valenzano
Journal: Molecular Therapy (2009)

Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency in α-galactosidase A (α-Gal A) activity and subsequent accumulation of the substrate globotriaosylceramide (GL-3), which contributes to disease pathology. The pharmacological chaperone (PC) DGJ (1-deoxygalactonojirimycin) binds and stabilizes α-Gal A, increasing enzyme levels in cultured cells and in vivo. The ability of DGJ to reduce GL-3 in vivo was investigated using transgenic (Tg) mice that express a mutant form of human α-Gal A (R301Q) on a knockout background (Tg/KO), which leads to GL-3 accumulation in disease-relevant tissues. Four-week daily oral administration of DGJ to Tg/KO mice resulted in significant and dose-dependent increases in α-Gal A activity, with concomitant GL-3 reduction in skin, heart, kidney, brain, and plasma; 24-week administration resulted in even greater reductions. Compared to daily administration, less frequent DGJ administration, including repeated cycles of 4 days with DGJ followed by 3 days without or every other day with DGJ, resulted in even greater GL-3 reductions that were comparable to those obtained with Fabrazyme. Collectively, these data indicate that oral administration of DGJ increases mutant α-Gal A activity and reduces GL-3 in disease-relevant tissues in Tg/KO mice, and thus merits further evaluation as a treatment for Fabry disease. Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency in α-galactosidase A (α-Gal A) activity and subsequent accumulation of the substrate globotriaosylceramide (GL-3), which contributes to disease pathology. The pharmacological chaperone (PC) DGJ (1-deoxygalactonojirimycin) binds and stabilizes α-Gal A, increasing enzyme levels in cultured cells and in vivo. The ability of DGJ to reduce GL-3 in vivo was investigated using transgenic (Tg) mice that express a mutant form of human α-Gal A (R301Q) on a knockout background (Tg/KO), which leads to GL-3 accumulation in disease-relevant tissues. Four-week daily oral administration of DGJ to Tg/KO mice resulted in significant and dose-dependent increases in α-Gal A activity, with concomitant GL-3 reduction in skin, heart, kidney, brain, and plasma; 24-week administration resulted in even greater reductions. Compared to daily administration, less frequent DGJ administration, including repeated cycles of 4 days with DGJ followed by 3 days without or every other day with DGJ, resulted in even greater GL-3 reductions that were comparable to those obtained with Fabrazyme. Collectively, these data indicate that oral administration of DGJ increases mutant α-Gal A activity and reduces GL-3 in disease-relevant tissues in Tg/KO mice, and thus merits further evaluation as a treatment for Fabry disease.
Abstract 4820: Whole methylome explorations of paired tumor and non-tumor clinical samples using HELP
Authors: Nandita Mullapudi, Miao Shi, Masako Suzuki, Simon Spivack
Journal: Cancer Research (2011)

Abstract Introduction: Gene silencing by promoter methylation is common in carcinogenesis. In lung cancer, hypermethylation of specific gene promoters has been found to occur during the earliest histologic stages of the cancer. Thus far surveys of methylation in lung tumors have focused on specific gene panels (5 – 10 genes). A few large scale studies have reported selection of longer gene lists or focused on larger sets of CpG islands. Methods: We have adapted an approach to survey genome-wide methylation events in tumor and adjacent non-tumor tissue from clinical lung resection samples using the HELP (HpaII tiny fragment Enrichment by Ligation mediated PCR) assay. This assay, based on the generation of restriction enzyme libraries generated by methylation sensitive (HpaII) and methylation insensitive (MspI) isoschizomers yields information on 1.2 million HpaII fragments throughout the genome. Each HpaII fragment corresponds to two CpG sites. The assay lends itself to low starting amounts of DNA (3 ug) and robust assessment of methylation status by comparing ratios of HpaII- generated- fragments to MspI- generated fragments co-hybridized to a Nimbelgen custom high-density microarray. Summary of results: In a pilot set of three paired tumor and non-tumor tissue samples, we identified 1504 fragments (corresponding to two CpG sites each) that were hypermethylated in tumor versus non-tumor in all three pairs. Of these, 165 fragments were located within gene promoters. In the opposite direction, 2907 fragments were found to be hypermethylated in non-tumor versus tumor. Of these, 81 were located within gene promoters. We could identify both known and novel regions of the genome as well as specific gene-promoters that are hypermethylated in tumor versus non-tumor. We will discuss selected methylation events in further detail. Conclusion: The HELP assay is a powerful approach to interrogate methylation status of individual HpaII fragments across the whole genome, offering a large sample size of 1.2 million HpaII fragments. We are able to discover individual methylation events common across different clinical specimens and are currently expanding our sample set, and planning correlations with transcriptome-wide studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4820. doi:10.1158/1538-7445.AM2011-4820
Mass Screening for Untreated Atrial Fibrillation
Authors: Emma Svennberg, Johan Engdahl, Faris Al-Khalili, Leif Friberg, Viveka Frykman, Mårten Rosenqvist
Journal: Circulation (2015)

Background— The aims of the present study were to define the prevalence of untreated atrial fibrillation (AF) in a systematic screening program using intermittent ECG recordings among 75- to 76-year-old individuals and to study the feasibility of initiating protective oral anticoagulant (OAC) treatment. Methods and Results— Half of the 75- to 76-year-old population in 2 Swedish regions were invited to a screening program for AF. Participants without a previous diagnosis of AF underwent intermittent ECG recordings over 2 weeks. If AF was detected, participants were offered OAC. During the 28-month inclusion period, 13 331 inhabitants were invited. Of these, 7173 (53.8%) participated. Of the participants, 218 (3.0%; 95% confidence interval [CI], 2.7–3.5) were found to have previously unknown AF, and of these, AF was found in 37 (0.5% of the screened population) on their first ECG. The use of intermittent ECGs increased new AF detection 4-fold. A previous diagnosis of AF was known in 9.3% (n=666; 95% CI, 8.6–10.0). Total AF prevalence in the screened population was 12.3%. Of participants with known AF, 149 (2.1%; 95% CI, 1.8–2.4) had no OAC treatment. In total, 5.1% (95% CI, 4.6–5.7) of the screened population had untreated AF; screening resulted in initiation of OAC treatment in 3.7% (95% CI, 3.3–4.2) of the screened population. More than 90% of the participants with previously undiagnosed AF accepted initiation of OAC treatment. Conclusions— Mass screening for AF in a 75- to 76-year-old population identifies a significant proportion of participants with untreated AF. Initiation of stroke prophylactic treatment was highly successful in individuals with newly diagnosed AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01593553.
Chemical constituents and ACE inhibitory activity of desert plant Suaeda physophora Pall.
Authors: Ruizhi Men, Ning Li, Yachao Xing, Yingzhan Tang, Chengyu Tan, Fantong Meng, Juan Zhang, Hui Ni, Xiaoguang Jia
Journal: Acta Pharmaceutica Sinica B (2013)

Suaeda physophora Pall. is a kind of desert plant mostly growing in saline habitats in Xinjiang Uygur Autonomous Region. In order to have a better utilization of halophytes, a screening for ACE inhibitors from halophytes growing in Xinjiang was carried out. The result showed that the 70% EtOH extract and n-BuOH extract of S. physophora Pall. possessed significant ACE inhibitory activities. So we focused on its biochemical constituents firstly. One new quinazoline alkaloid, namely Suaedine (1), along with six known compounds (2–7) was isolated from the aerial parts of S. physophora Pall. The structure of the new quinazoline alkaloid was established by one- and two-dimensional nuclear magnetic resonance, optical rotation and mass spectrometry analysis. The flavonoid compounds (2–4) and phenolic compound (5) exhibited significant ACE activities. It was the first time to focus on the chemical constituents and bioactivities of this plant.
ELECTROSURGERY IN THYROIDECTOMY
Authors: HARRY E. MOCK
Journal: JAMA (1930)

Electrosurgery, sometimes referred to as "surgical diathermy" or the "radio-knife," has been used with increasing frequency during the last decade in the treatment of malignant conditions. The use of the actual cautery, of the electric cautery and of the form of electrical surgery known as "fulguration" in far advanced cases of cancer, and even as the operation of choice in early operable cancer by some surgeons, has been a recognized procedure for several decades. The chief advantage of this method of attack lay in the blocking or sealing of the lymphatics and smaller blood vessels, thus aiding in the prevention of metastases or the escape of carcinomatous cells into other parts of the body during the actual process of cutting into or around the malignant growth. Other advantages noted were the better hemostasis obtained by this method of operating, the freedom from pain after operation, and the absence of shock.
Nystagmus in Otherwise Normal Coal-miners
Authors: R. C. Browne, I. F. Beck
Journal: BMJ (1954)

For years the popular opinion of coal-miners' nystagmus has been that it is a psychological disease and that the men are hysterical, anxious, obsessional, pathologically truculent, or, indeed, doubtfully genuine (Culpin, 1932). Moreover, Halliday (1948) has implied that the disease is  psychosocial. On the other hand, a previous study (Browne et al., 1950) suggested that miners who develop the disease are very much like those who do not. In the first comparison the men were certified in 1942, and in the second, which is described in this paper, in 1950, so that any reproducibility of the main results after a period of eight years and in different groups of men may lend some weight to the original conclusions. The problem in this disease is to. apportion the cause between the physical conditions of the miner's work and the psychological and social setting of his life.
Treatment of Impotence: A Coitus-training Apparatus
Authors: J. Loewenstein
Journal: BMJ (1941)

ache in the mornings.He fainted the day after discharge and was readmitted with no abnormal signs but symptoms of headache and depressioni.After a period of three weeks' convalescence he seemed.to be well again.Treatment It was only natural to give sulphapyridine to cases showing meningeal symptoms.-If the cerebrospinal fluid is not clear there can be little justification for withholding a drug which may be life-saving.Only the first three cases in which the fluid was not clear received the drug, 9, 8, and 6 grammes being given in the twenty-four hours.Vomit- ing, headache, and depression were made worse and recovery was delayed.Certainly those patients not receiv- ing sulphapyridine recovered more quickly.Eventually treatment was mainly symptomatic-aspirin and phenacetin, with copious glucose and fruit drinks.A wash-out of the stomach on the third day with bicarbonate and an enema seemed to give much relief.CommentsMumps is a virus infectiorn probably spreading via the blood stream and therefore able to affect any part of the body, with a predilection for the parotid gland.In the epidemic described the number of cases of mumps with complications was high.The percentage of all cases of patients developing meningeal symptoms in the epidemic was difficult to judge, but of those admitted to hospital 30% had signs and symptoms of meningeal involvement.It is possible that the particular virus was of a neurotrophic type.The meningeal symptoms have been described as due to the parotid gland compressing the internal jugular vein.This can be discounted because not all cases have a parotitis.In the cases described no polymorphonuclear leucocytes were seen in the cerebrospinal fluid; it is there- fore to be expected that sulphonamides will not alter the course of the disease.A guinea-pig received some of the cerebrospinal fluid from Case 5 intracerebrally: no rise of temperature and no apparent ill effects ensued.
Ubiquitination of red blood cell α‐spectrin does not affect heterodimer formation
Authors: Mahnoush H. Riahi, David G. Kakhniashvili, Steven R. Goodman
Journal: American Journal of Hematology (2005)

Abstract Erythrocyte α‐spectrin is ubiquitinated in repeats α20/α21, which also represents the nucleation site for contact with the β subunit which leads to heterodimer formation by a zippering mechanism. In this study we have determined the second‐order rate constant for association of ubiquitinated α′‐spectrin, nonubiquitinated α‐spectrin, and β‐spectrin into the α′β or αβ heterodimer. The rate constant for incorporation of monomers into heterodimers at 37°C were (5.181 ± 0.001) × 10 5 M −1 sec −1 for total α‐spectrin (α + α′), (5.121 ± 0.001) × 10 5 M −1 sec −1 for α′‐spectrin, and (5.178 ± 0.003) × 10 5 M −1 sec −1 for β‐spectrin. We conclude that ubiquitination of α‐spectrin does not regulate heterodimer formation. Am. J. Hematol. 78:281–287, 2005. © 2005 Wiley‐Liss, Inc.
Pulmonary response of fifth component of complement-sufficient and -deficient mice to hyperoxia.
Authors: D A Parrish, B C Mitchell, P M Henson, G L Larsen
Journal: Journal of Clinical Investigation (1984)

The fifth component of complement, C5, can form fragments that cause neutrophil chemotaxis, oxygen radical production, and lysosomal enzyme release. The purpose of this study was to determine if C5 and these fragments contribute to the inflammation seen in pulmonary oxygen toxicity as defined by histology and analysis of bronchoalveolar lavage fluid (BALF). In addition, the role of C5 in producing mortality in the animals was addressed. Pairs of C5 deficient (C5-) and C5 sufficient (C5+) mice, 6 mo or older, were placed in a chamber and challenged with 95% oxygen at ambient pressure. A significant difference in mortality was observed after 200 h of exposure, i.e., 90% mortality in C5+ mice vs. 25% mortality in C5- mice (P less than 0.001). This difference in mortality was not seen when C5- mice were transfused with plasma that contained C5 derived from C5+ mice. Morphometric analysis of histologic sections with light microscopy revealed earlier pathologic changes in C5+ mice that was characterized by increased cellularity due in part to neutrophil influx into the alveolar-capillary wall. Transmission electron microscopy also confirmed an earlier inflammatory response in the C5+ mice with evidence of injury to alveolar epithelial cells, interstitial edema, and an increase in the cellular component of the interstitium. Analysis of BALF also demonstrated earlier abnormalities in C5+ mice, which included a significantly greater percentage of neutrophils in the C5+ mice at 117 h. Similar studies in younger mice of these strains again showed earlier neutrophil accumulation in C5+ mice, but the time course of the injury was more protracted. This study shows that the presence of C5 is associated with a greater mortality and an earlier influx of neutrophils into murine lungs. However, in the absence of C5, neutrophils will still immigrate into the lung and hyperoxic damage will occur at a later time point, which demonstrates the inherent redundancy of the inflammatory process.
Pericardial tamponade preceding cutaneous involvement in systemic sclerosis.
Authors: C Perez-Bocanegra, V Fonollosa, C P Simeon, J Candell, R Solans, A Gomez, M Vilardell
Journal: Annals of the Rheumatic Diseases (1995)

HLA-DR and DQ antigen frequencies observed in SLE patients and controls from Singapore Antigen SLE Controls (n = 26) (n = 77) n % n 30 7 25 32-5*X2= 0 99; odds ratio 2-0; 95% confidence interval 0-51 to 7-83; p = 009.also a non-significant increase in DR8.4However, our most striking finding was the absence of a DR2 association with SLE, as this had been found in the studies from Hong Kong and Korea4 5 and in a further study from Kuala Lumpur, Malaysia.6One possible explanation for these differences could be genetic admixture in the Singapore Chinese population, as there has been some intermarriage with Malays, Indians, and Europeans since the seven- teenth century.In contrast, Hong Kong Chinese rarely marry non-Chinese.This could explain the presence in the Singapore SLE patients of the typical white population SLE susceptibility haplotype carrying DR3 and DQ2.Another explanation could be ethnic heterogeneity among the southern Chinese.In Singapore, for example, approximately 75% of the Chinese migrated from Furjian Province, whereas 90% or more of the Hong Kong Chinese came from Guangdong Province.Unfortunately, the HIA distributions in these populations are not well characterised, but there may be significant differences which could have implications for the relative frequencies of MHC haplotypes (particularly DR2) predisposing to SLE in these populations.
Focus: Brussels: A little glimpse of ethics for the union
Authors: R Watson
Journal: BMJ (1994)

The business of ethics is not something one naturally associates with the European Union. The union conjures up images of political, economic, and social discussion, leaving intellectual debate on ethics to others. But that image is not entirely accurate: for the past two years a high powered group of advisers has been giving the European Commission the benefit of its collective wisdom on the ethical implications of biotechnology. It is now about to assume a much more public profile.

The guiding force behind the group's creation was Jacques Delors, the commission president. He signalled his intention in a speech at Strasbourg five years ago. As he said then: “The ethical dimension is once again coming to the fore, and we must step up the debate about these fundamental issues which concern the very essence of human life and society.” …
Artificial Atrial and Ventricular Pacing in the Treatment of Arrhythmias
Authors: Douglas P. Zipes, Andrew G. Wallace, Will C. Sealy, Walter L. Floyd
Journal: Annals of Internal Medicine (1969)

Five patients with various types of arrhythmias refractory to standard therapeutic agents are presented, and the therapeutic approach to the control of these arrhythmias is outlined. The possible electrophysiologic mechanisms operative are discussed in detail. The most important aspect of artificial pacing is the prevention of arrhythmias that are incompatible with life: ventricular asystole and ventricular fibrillation. Important additional benefits of pacing include the control of less threatening but symptomatic tachyarrhythmias and bradyarrhythmias and the preservation of the best hemodynamic and electrophysiologic relationships possible. Pacing allows the concomitant use of drugs to control tachyarrhythmias without fear of suppressing intrinsic impulse formation and producing asystole. Because of the varied modes of pacing available, it is imperative that each patient be evaluated carefully and that a type of pacing be selected that best serves his needs.
LONG LATENCY PRECEDES OVERT SEROCONVERSION IN SEXUALLY TRANSMITTED HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION
Authors: Annamari Ranki, Minerva Krohn, Jean-Pierre Allain, Genoveffa Franchini, Sirkka-Liisa Valle, Jaakko Antonen, Michael Leuther, Kai Krohn
Journal: The Lancet (1987)
Helicobacter pylori: the African enigma.
Authors: C Holcombe
Journal: Gut (1992)

H-elicobacter pylori: the African enigma Data on Helicobacter pylori infection in Africa are at odds in several aspects with those published in the west.Gastric H pyloni infection is common, almost ubiquitous in Africa, but the pattern of infection, age of acquisition, environmen- tal, dietary, and genetic influences are different from those in the west.These differences alter the pathological role and clinical relevance of the organism in Africa where, apart from gastritis, there is no established correlation between H pyloni infection and upper gastrointestinal disease.
XmnIGγ-polymorphism in six unrelated Pakistani families with Inv/DelGγ(Aγδβ)° δβ-thalassemia
Authors: Suhaib Ahmed, Masood Anwar
Journal: American Journal of Hematology (2005)

The XmnI Gγ-polymorphism (C–T polymorphism at position −158 to the Gγ-globin gene) was studied in 13 individuals from six unrelated Pakistani families with δβ-thalassemia. All of the subjects had the Asian-Indian Inv/Del Gγ(Aγδβ)° that included six heterozygotes, six homozygotes, and one compound heterozygote of δβ- and β-thalassemia. All seven δβ-thalassemia heterozygotes (including one compound heterozygote) had the −/+ genotype, whereas all six of the homozygotes had the +/+ genotype. The results strongly suggest a tight linkage between the XmnI Gγ-polymorphism and the Asian-Indian Inv/Del Gγ(Aγδβ)°. The finding could explain the unusually well-preserved capacity to produce fetal hemoglobin in δβ-thalassemia. Am. J. Hematol. 80:303–305, 2005. © 2005 Wiley-Liss, Inc.
Danazol and benign intracranial hypertension.
Authors: A Shah, T Roberts, I N McQueen, J G Graham, K Walker
Journal: BMJ (1987)

10% of maternal deaths, and the reported mortality is as high as 80% in some series.2Amniotic fluid embolism may occur after diagnostic amniocentesis, but this is uncommon.It is more likely to occur after hypertonic saline or dextrose is injected into the amniotic fluid.'In our patient exchange transfusion allowed rapid removal of red cell debris and haemoglobin from the circulation and provided red cells and clotting factors in fresh plasma.ABO incompatibility between fetal and maternal blood groups appears to have contributed to the severity ofour patient's condition; this was similar to the reaction that would be expected after transfusion of ABO incompatible blood.The complete disappearance of a high titre of anti-B immediately after the suspected embolism gives indirect evidence that the rapid deterioration was due to amniotic fluid embolism.Amniotic fluid is known to contain fetal blood group substances,4 and the findings above may be relevant to experiments in which amniotic fluid was injected into animals in an attempt to define the pathogenesis.5We believe that exchange transfusion helped to change the course of events and contributed to a successful outcome in this patient.
Liposome-mediated transfer of nitric oxide synthase gene improves renal function in ureteral obstruction in rats1
Authors: Keiichi Ito, Jie Chen, Jonathan J. Khodadadian, Surya V. Seshan, Christian Eaton, Xinyu Zhao, E. Darracott Vaughan, Michael Lipkowitz, Dix P. Poppas, Diane Felsen
Journal: Kidney International (2004)
Hypersensitivity to pollen of <i>Olea europaea</i> in Israel
Authors: C. Geller‐Bernstein, G. Arad, N. Keynan, C. Lahoz, B. Cardaba, V. Waisel
Journal: Allergy (1996)

The incidence of skin‐tested sensitivity to olive pollen allergens among subjects with suspected atopic respiratory allergy was investigated in various populations of Israelis. This incidence was correlated with the olive cultivars, with the abundance of trees in the patients' neighborhoods, and with the history of exposure of the studied populations to olive pollen. Positive skin reactions to olive pollen, among atopic patients of the Jewish population, is rather high where olive trees are abundant (66%), and lower (29%) where trees are scarce (P&lt;0.003). Sensitization was significantly lower ( P&lt; 0.003) among a population of Israeli atopic Arabs (16%), though these Arabs have lived in an olive‐rich area for several generations.