tbuckley/cabot-search huggingface dataset:
Movement of Genes in Nucleus May Someday Aid Diagnosis
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (2010)

When researchers realized a decade ago that genes inhabit a specific space within a cell’s nucleus and that they sometimes change location during differentiation and in certain diseases, they began to contemplate why. Tom Misteli, Ph.D., and his group at the National Cancer Institute are now asking whether they can exploit evidence of gene movement as a diagnostic tool. In a preliminary study comparing 14 invasive breast cancer tissue samples with 11 healthy breast tissue samples, the researchers found that several genes have a different physical position in the nucleus in invasive breast cancer. One gene, HES5, known to affect pathways involved in cancer, allowed identifi cation of invasive breast cancer in more than 90% of cases. The fi ndings were published in the December 14, 2009, Journal of Cell Biology . Today pathologists look through a microscope in search of distinctive changes in shape and size of the cell nucleus as signs of cancer. But the Misteli group’s approach is different because it’s quantitative and spatial. They use fl uorescence in situ hybridization to label specifi c genes in an intact nucleus. Using little tissue, just 100 – 200 cells, they can compare gene position in biopsy tissue against a standardized normal. “To the best of my knowledge, we are the only group trying to utilize the position of genes for diagnostic purposes,” said Karen Meaburn, Ph.D., in Misteli’s lab in NCI’s Center for Cancer Research. The approach makes sense to Mark T. Groudine, M.D., Ph.D., who studies gene positioning during differentiation of hematopoietic stem cells, which shifts as the precursor cells become red blood cells or white blood cells. “This may be a simple way of trying to determine if cells are normal or cancerous based on the positioning of chromosomes or genes,” says Groudine, deputy director of the Fred Hutchinson Cancer Research Center in Seattle. “It’s a very nice model.” “What’s so exciting about Karen’s paper is it’s a large number of genes and she did it in tumor biopsies,” says Joanna M. Bridger, Ph.D., deputy director of the Centre for Cell and Chromosome Biology at Brunel University in West London. “The data are so nice that she can make that correlation with diagnosis.” Meaburn did her doctoral studies in Bridger’s lab.
Physiological antagonism between endogenous CCK and opioid: Clinical perspectives in the management of pain
Authors: Florence Noble, Rafaël Maldonado, Bernard P. Roques
Journal: Behavioral and Brain Sciences (1997)

Numerous mediators are involved in both the control and the transmission of nociceptive messages, and several lines of research have been developed in the management of pain. Complete enkephalin- degrading enzyme inhibitors, which produce naloxone-reversible analgesia in all tests where morphine has been found to be active, remains the most promising way. CCK compounds, especially the CCK B antagonists also may be interesting drugs. Indeed, they are able to strongly potentiate the antinociceptive effects of the opioids. [dickenson, wiesenfeld-hallin et al.]
Progressive Anterior Ablation in the Coronary Sinus Region
Authors: Andrew D. Krahn, George J. Klein, Raymond Yee, Magdy N. Basta, John K. Lee
Journal: Circulation (1997)

Background AV node modification is an emerging approach to rate control in patients with medically refractory atrial fibrillation. The mechanism of benefit of this procedure is not completely understood. Methods and Results Twenty-two patients (age, 65±11 years; 16 women) with medically refractory paroxysmal atrial fibrillation referred for complete AV node ablation underwent serial ablations beginning at the level of the coronary sinus os progressing in a superior and anterior direction toward the His bundle. Serial atrial extrastimulus testing was performed to determine the effect of the progressive posteroseptal ablation in the region of the coronary sinus on the AV node antegrade refractory curve. Two of 22 patients had antegrade dual AV node pathways before ablation. Three patterns of response to serial ablation were noted. In 10 patients (45%), loss of the terminal portion of the AV node antegrade refractory curve occurred without evidence of fast pathway injury. In 7 patients (32%) the curve was shifted upward and to the left, consistent with nonspecific AV node damage. In 5 patients (23%), no effect could be attained before induction of complete AV block at superior and anterior ablation sites. Clinical variables and site of ablation did not predict response to serial ablations. Conclusions These data suggest that the mechanism of benefit of AV node modification in this population may be through elimination of “slow pathway” tissue in half of patients and nonspecific injury in the remainder. Modification without complete AV block may not be possible in a minority of patients, as the response to progressive ablation appears to be “all or none” conduction.
Response to Comment on: van Dijk et al. Exercise Therapy in Type 2 Diabetes: Is Daily Exercise Required to Optimize Glycemic Control? Diabetes Care 2012;35:948–954
Authors: Jan-Willem van Dijk, Luc J.C. van Loon
Journal: Diabetes Care (2013)

We thank Thosar and Wallace (1) for their interest and constructive comment related to our recent work published in Diabetes Care (2). As this was the first study that investigated the impact of the frequency of exercise (within a fixed volume) on glycemic control, we specifically designed a short-term intervention study during which glycemic control was assessed over 48 h with exercise and dietary conditions being strictly standardized. The short-term nature of our study allowed for the assessment of the effects of exercise per se, without changes in dietary intake and habitual physical activity, or changes in body weight and/or composition. As …
An absence of alcohol policy
Authors: D. Cameron, J. Chick, D. Raistrick, M. Rake, T. Spratley, A. Thorley, J. Werner
Journal: BMJ (1983)

<h3>Abstract</h3> We present a novel way to enhance the information content of fluorescence imaging by encoding information in the microscope point-spread function (PSF). In contrast to methods that modify the shape of the PSF itself, our approach encodes the additional information via the creation of faithful copies of the original PSF. Our method is compatible with operation over a broad wavelength range, other PSF engineering modalities, and existing analysis tools. We demonstrate this approach by developing the ‘Circulator’, an optical add-on made of off-the-shelf components that encodes the emission band of the fluorophore into the PSF. The device creates four copies of the original PSF at well-defined relative orientations and positions, where the presence or intensity of each spot indicates the emission color of the fluorophore. Using this device, simultaneous multicolor super-resolution and single-molecule microscopy can be performed using the full field of view of a single camera, resulting in a pronounced increase in experimental throughput. We demonstrate our approach in simultaneous three-color super-resolution imaging with single-molecule localization microscopy (SMLM) and super-resolution optical fluctuation imaging (SOFI).
Do general practitioners miss dementia in elderly patients?
Authors: D. W. O'Connor, P. A. Pollitt, J. B. Hyde, C. P. Brook, B. B. Reiss, M. Roth
Journal: BMJ (1988)

Cocaine-driven changes in the modulation of neurotransmission by neuromodulators are poorly understood. The ventral pallidum (VP) is a key structure in the reward system, in which GABA neurotransmission is regulated by opioid neuropeptides, including dynorphin. However, it is not known whether dynorphin acts differently on different cell types in the VP and whether its effects are altered by withdrawal from cocaine. Here, we trained wild-type, D1-Cre, A2A-Cre, or vGluT2-Cre:Ai9 male and female mice in a cocaine conditioned place preference protocol followed by 2 weeks of abstinence, and then recorded GABAergic synaptic input evoked either electrically or optogenetically onto identified VP neurons before and after applying dynorphin. We found that after cocaine CPP and abstinence dynorphin attenuated inhibitory input to VP<sub>GABA</sub> neurons through a postsynaptic mechanism. This effect was absent in saline mice. Furthermore, this effect was seen specifically on the inputs from nucleus accumbens medium spiny neurons expressing either the D1 or the D2 dopamine receptor. Unlike its effect on VP<sub>GABA</sub> neurons, dynorphin surprisingly potentiated the inhibitory input on VP<sub>vGluT2</sub> neurons, but this effect was abolished after cocaine CPP and abstinence. Thus, dynorphin has contrasting influences on GABA input to VP<sub>GABA</sub> and VP<sub>vGluT2</sub> neurons and these influences are affected differentially by cocaine CPP and abstinence. Collectively, our data suggest a role for dynorphin in withdrawal through its actions in the VP. As VP<sub>GABA</sub> and VP<sub>vGluT2</sub> neurons have contrasting effects on drug-seeking behavior, our data may indicate a complex role for dynorphin in withdrawal from cocaine. <b>SIGNIFICANCE STATEMENT</b> The ventral pallidum consists mainly of GABAergic reward-promoting neurons, but it also encloses a subgroup of aversion-promoting glutamatergic neurons. Dynorphin, an opioid neuropeptide abundant in the ventral pallidum, shows differential modulation of GABA input to GABAergic and glutamatergic pallidal neurons and may therefore affect both the rewarding and aversive aspects of withdrawal. Indeed, abstinence after repeated exposure to cocaine alters dynorphin actions in a cell-type-specific manner; after abstinence dynorphin suppresses the inhibitory drive on the "rewarding" GABAergic neurons but ceases to modulate the inhibitory drive on the "aversive" glutamatergic neurons. This reflects a complex role for dynorphin in cocaine reward and abstinence.
Critical role of the neutrophil-associated high-affinity receptor for IgE in the pathogenesis of experimental cerebral malaria
Authors: Adeline Porcherie, Cedric Mathieu, Roger Peronet, Elke Schneider, Julien Claver, Pierre-Henri Commere, Hélène Kiefer-Biasizzo, Hajime Karasuyama, Geneviève Milon, Michel Dy, Jean-Pierre Kinet, Jacques Louis, Ulrich Blank, Salaheddine Mécheri
Journal: The Journal of Experimental Medicine (2011)

The role of the IgE-FcεRI complex in malaria severity in Plasmodium falciparum-hosting patients is unknown. We demonstrate that mice genetically deficient for the high-affinity receptor for IgE (FcεRIα-KO) or for IgE (IgE-KO) are less susceptible to experimental cerebral malaria (ECM) after infection with Plasmodium berghei (PbANKA). Mast cells and basophils, which are the classical IgE-expressing effector cells, are not involved in disease as mast cell-deficient and basophil-depleted mice developed a disease similar to wild-type mice. However, we show the emergence of an FcεRI(+) neutrophil population, which is not observed in mice hosting a non-ECM-inducing PbNK65 parasite strain. Depletion of this FcεRI(+) neutrophil population prevents ECM, whereas transfer of this population into FcεRIα-KO mice restores ECM susceptibility. FcεRI(+) neutrophils preferentially home to the brain and induce elevated levels of proinflammatory cytokines. These data define a new pathogenic mechanism of ECM and implicate an FcεRI-expressing neutrophil subpopulation in malaria disease severity.
Effects of quinapril, a new angiotensin converting enzyme inhibitor, on left ventricular failure and survival in the cardiomyopathic hamster. Hemodynamic, morphological, and biochemical correlates.
Authors: S J Haleen, R E Weishaar, R W Overhiser, R F Bousley, J A Keiser, S R Rapundalo, D G Taylor
Journal: Circulation Research (1991)

The effect of chronic therapy with quinapril on the temporal progression of left ventricular failure and survival was assessed in the CHF 146 cardiomyopathic (CM) hamster, which is an idiopathic model of congestive heart failure. Age-matched Golden Syrian (GS) hamsters served as normal controls. Quinapril was administered in the drinking water at average daily doses of 10.2, 112.4, and 222.4 mg/kg/day. In untreated CM hamsters, in vitro left ventricular performance progressively deteriorated with increasing age beginning at roughly 180 days. This decline in left ventricular performance was accompanied by a decrease in coronary flow and an increase in left ventricular volume. Administration of quinapril from 180 to 300 days of age prevented the decline of in vitro left ventricular contractile performance and coronary flow and also reduced the age-dependent increases in left ventricular volume. The cardioprotective effects of quinapril were observed at doses of 112.4 and 222.4 mg/kg/day but not at 10.2 mg/kg/day. Lung angiotensin converting enzyme activity was significantly inhibited by quinapril in GS and CM hamsters at 240 and 300 days of age at all dose levels. In contrast, significant inhibition of ventricular angiotensin converting enzyme activity was observed consistently at doses of 112.4 and 222.4 mg/kg/day quinapril but not at 10.2 mg/kg/day. In the survival protocol, CM and GS hamsters were treated with vehicle or quinapril (100 mg/kg/day) from 180 to 522 days of age. During the initial 210 days of treatment (from 180 to 390 days of age) 78.3% of the vehicle-treated CM hamsters died compared with 27.7% of quinapril-treated CM hamsters. Quinapril increased the median survival time of CM hamsters by 32.9% (112 days). It is concluded that chronic quinapril therapy exerts a significant cardioprotective effect and also increases survival.
Fibroblasts Can Be Genetically Modified to Produce Excitable Cells Capable of Electrical Coupling
Authors: Eddy Kizana, Samantha L. Ginn, David G. Allen, David L. Ross, Ian E. Alexander
Journal: Circulation (2005)

Cardiac conduction occurs in an electrical syncytium of excitable cells connected by gap junctions. Disruption of these electrophysiological properties causes conduction slowing or block. Depending on the location of affected cells within the heart, this has the potential to result in clinical syndromes such as atrioventricular block. With a view to developing gene therapy strategies for repairing cardiac conduction defects, we sought to establish whether the phenotype of fibroblasts can be modified by gene transfer to produce cells capable of electrical excitation and coupling.High-titer lentiviral vectors encoding MyoD, a myogenic transcription factor, and connexin43, a gap junction protein, were produced by established methods. Human dermal fibroblasts (HDFs) were efficiently (>80%) transduced at a multiplicity of infection of 50. HDFs transduced with the MyoD-encoding vector underwent myogenic conversion, as evidenced by myotube formation and detection of muscle-specific proteins. Importantly, calcium transients indicative of membrane excitability were observed in MyoD-induced myotubes after loading with a calcium-sensitive dye and electrical stimulation. Transients from adjacent myotubes displayed different excitation thresholds, indicating an absence of coupling between cells, consistent with skeletal muscle biology. In contrast, simultaneous transduction of HDFs with MyoD and connexin43-encoding vectors resulted in the appearance of transients in adjacent myotubes with identical thresholds, indicative of electrical coupling. Notably, dye transfer studies confirmed gap junctional intercellular communication.Fibroblasts can be genetically modified to produce excitable cells capable of electrical coupling. These observations strengthen the prospect of developing gene-based strategies for repairing cardiac conduction defects.
Recognition and characterization of stage-specific oocyst/sporozoite antigens of Toxoplasma gondii by human antisera.
Authors: L H Kasper, P L Ware
Journal: Journal of Clinical Investigation (1985)

Human infection with Toxoplasma gondii is presumed due to the ingestion of either tissue cysts containing bradyzoites or oocyst/sporozoites that are excreted in the feces of infected cats. The incidence of human infection in the general population by either of these routes is unknown. We have previously described unique stage-specific oocyst/sporozoite antigens identified by murine hybridoma monoclonal antibodies. We obtained acute and convalescent antitoxoplasma antisera from patients in an epidemiologically well-documented outbreak of oocyst-transmitted infection associated with the ingestion of contaminated water. An enzyme-linked immunosorbent assay comparing equal numbers of tachyzoites (invasive stage) and oocyst/sporozoite (excreted stage) indicated that these antisera recognized antigens from both life forms. Absorption of pooled antisera with purified oocyst/sporozoites reduced both the antioocyst immunoglobulin G (IgG) and immunoglobulin M (IgM) titer but had only minimal effect on the antitachyzoite titer. Absorption of the antisera with tachyzoites reduced the IgG and IgM antioocyst and antitachyzoite titer. A sodium dodecyl sulfate-polyacrylamide gel analysis of radioiodinated oocyst/sporozoites shows that the principal stage-specific surface proteins of the oocyst/sporozoite have approximate Mr of 67,000 and 25,000. Periodic acid and silver stain of purified oocyst/sporozoite identified bands of similar molecular weight not present in the tachyzoite preparation. Western blot analysis of purified parasites assayed with human antioocyst antisera identified specific oocyst/sporozoite antigens not present on the tachyzoites. At least two major stage-specific oocyst/sporozoite antigens of approximate Mr of 67,000 and 190,000 were identified by the infected patients' antisera and not by the normal controls. Reaction to these oocyst/sporozoite antigens was seen primarily in the IgM fraction of the acute phase and the IgG fraction of convalescent phase antisera. Neither absorption of the antisera with tachyzoites nor periodate treatment of the oocyst/sporozoites reduced the antibody recognition of these stage-specific antigens. These data suggest that individuals infected by a presumed oocyst-transmitted route develop antibodies against unique stage-specific oocyst/sporozoite antigens.
Thrombotic Thrombocytopenic Purpura in Pregnancy
Authors: Walter Solomon
Journal: JAMA (1963)

THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) is being diagnosed with increasing frequency. Five cases have been reported in which the disease occurred as a complication of pregnancy.1-4We are here presenting a synopsis of these cases and are adding a sixth case together with a discussion of diagnosis and management.  Report of a Case  On Jan 20, 1961, a 28-yr-old pregnant woman, Gravida 6, Para 4, whose expected date of confinement was Feb 20, came to The Bronx Hospital in active labor. Fifteen minutes after admission a 4 lb 6 oz (2.0 kg) girl was delivered spontaneously. Intrapartum bleeding was estimated at less than 150 cc. The only notable signs at this time were pallor (Table 1) and a blood pressure of 140/90 mm Hg. A blood transfusion had to be discontinued after 800 cc because of a chill and vomiting. Rectal temperature was 100 F (37.8 C) and pulse rate
Ulcerative colitis: sclerosing cholangitis today, cancer tomorrow?
Authors: ULRIKA BROOMÉ, R W CHAPMAN
Journal: Gut (1997)

<h3>BACKGROUND:</h3> It is unclear whether intrauterine exposure to maternal diabetes is associated with risk factors for cardiovascular disease and related end points in adulthood. We examined this potential association in a population-based birth cohort followed up to age 35 years. <h3>METHODS:</h3> We performed a cohort study of offspring born between 1979 and 2005 (<i>n</i> = 293 546) and followed until March 2015 in Manitoba, Canada, using registry-based administrative data. The primary exposures were intrauterine exposure to gestational diabetes and type 2 diabetes mellitus. The primary outcome was a composite measure of incident cardiovascular disease events, and the secondary outcome was a composite of risk factors for cardiovascular disease in offspring followed up to age 35 years. <h3>RESULTS:</h3> The cohort provided 3 628 576 person-years of data (mean age at latest follow-up 20.5 [standard deviation 6.4] years, 49.3% female); 2765 (0.9%) of the offspring experienced a cardiovascular disease end point, and 12 673 (4.3%) experienced a cardiovascular disease risk factor. After propensity score matching, the hazard for cardiovascular disease end points was elevated in offspring exposed to gestational diabetes (adjusted hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.12–1.79) but not type 2 diabetes (adjusted HR 1.40, 95% CI 0.98–2.01). A similar association was observed for cardiovascular disease risk factors (gestational diabetes: adjusted HR 1.92, 95% CI 1.75–2.11; type 2 diabetes: adjusted HR 3.40, 95% CI 3.00–3.85). <h3>INTERPRETATION:</h3> Intrauterine exposure to maternal diabetes was associated with higher morbidity and risk related to cardiovascular disease among offspring up to 35 years of age.
Myocardial Infarction Due to Postirradiation Fibrosis of the Coronary Arteries
Authors: Malin R. Dollinger
Journal: JAMA (1966)

COMPLICATIONS of radiation therapy, which are more severe and disabling than the primary disease, may develop in patients with Hodgkin's disease. The major disability in a patient who survived for 18 years after diagnosis was due to an extreme degree of postirradiation fibrosis, resulting in elephantiasis of the legs, and coronary artery occlusion and acute myocardial infarction secondary to radiation-induced coronary artery fibrosis. To our knowledge, this latter complication of radiation therapy has not been previously described in detail, only two cases having been briefly discussed by Pearson.<sup>1</sup> <h3>Report of a Case</h3> A diagnosis of Hodgkin's disease was made in this patient at the age of 23 (1943) by biopsy of enlarged right inguinal lymph nodes. Over the next three years, he received radiation therapy to the axillary, cervical, inguinal, and abdominal areas. Elephantiasis and chronic cellulitis of the legs and scrotum developed, which was not improved after a
Advances in Rheumatic Fever, 1940-1961
Authors: B. M. Ansell
Journal: Annals of the Rheumatic Diseases (1964)

factors in the population have shown interesting differ- ences which may well throw light on the aetiology of rheumatoid arthritis, but other forms of rheumatism are not neglected.Of particular interest are contribu- tions on the less frequent causes of generalized osteo- arthrosis, such as ochronosis, gout, chondrocalcinosis, and Kashin-Beck's disease.