tbuckley/cabot-search huggingface dataset:
Rapid and highly efficient inducible cardiac gene knockout in adult mice using AAV-mediated expression of Cre recombinase
Authors: Stanislas Werfel, Andreas Jungmann, Lorenz Lehmann, Jan Ksienzyk, Raffi Bekeredjian, Ziya Kaya, Barbara Leuchs, Alfred Nordheim, Johannes Backs, Stefan Engelhardt, Hugo A. Katus, Oliver J. Müller
Journal: Cardiovascular Research (2014)

AimsInducible gene targeting in mice using the Cre/LoxP system has become a valuable tool to analyse the roles of specific genes in the adult heart. However, the commonly used Myh6-MerCreMer system requires time-consuming breeding schedules and is potentially associated with cardiac side effects, which may result in transient cardiac dysfunction. The aim of our study was to establish a rapid and simple system for cardiac gene inactivation in conditional knockout mice by gene transfer of a Cre recombinase gene using adeno-associated viral vectors of serotype 9 (AAV9).
Hepatic Uptake of Technetium-99m Diisopropyl Iminodiacetic Acid (DISIDA) is Not Impaired by Very High Serum Bilirubin Levels
Authors: SUSAN A. ASCHER, SALIL D. SARKAR, WILLIAM B. SPIVAK
Journal: Clinical Nuclear Medicine (1988)

The hepatic clearance of Tc-99m labeled iminodiacetic acid (IDA) compounds is believed to be impaired in patients with severe hyperbilirubinemia. Competitive inhibition of hepatocyte uptake of IDA by bilirubin has been demonstrated in vitro, but not by clinical scintigraphy. We present a patient with Crigler-Najjar syndrome without evidence of hepatobiliary damage, who demonstrated normal uptake and excretion of Tc-99m DISIDA despite a serum indirect bilirubin level in excess of 30 mg/dl. It is therefore suggested that a markedly elevated serum bilirubin level per se does not inhibit hepatic uptake of Tc-IDA and does not preclude clinically useful scintigraphic examination.
THE EXTENDED RADICAL MASTECTOMY
Authors: Warren Cole
Journal: JAMA (1964)

A communication in this issue (p 96) reports improved results after an extended radical mastectomy of the Urban type. This extended operation resulted from the initial work of R. S. Handley in London, and clinical application by Urban and others. As recorded by Sugarbaker in this recent study, the 5-year survival rate of 160 patients after the extended radical mastectomy was 70% during the period between 1951 and 1957, compared to a survival rate of 55% in 95 patients having conventional radical mastectomy between 1947 and 1951. Due to lay and professional education, patients with cancer of the breast in the 1951-1957 period might be expected to have come to the physician earlier than those in the 1947-1951 period. However, the percentage of patients with positive axillary nodes was only slightly lower in the later period, 53% as compared with 55% between 1947 and 1951. Though one surgeon performed all
Changing Prescribing Practices Through Individual Continuing Education-Reply
Authors: Phil R. Manning
Journal: JAMA (1987)

<h3>In Reply.—</h3> We appreciate the thoughtful comments of Drs Soumerai and Avorn. They have pointed out one of the difficulties of studies such as ours that depend on the continued cooperation of volunteer physicians. The loss of physicians from the study is one example of this kind of difficulty, and Drs Soumerai and Avorn rightly call attention to the limitations of tests of statistical significance in this situation. We do not agree, however, with their assertion that the findings of this study are in sharp disagreement with other work in the field. Basically, we demonstrated that when an educational program is individualized, whether done in person (as with their work) or by a written response (as with ours), physicians can and will change their behaviors. When printed materials are sent without involvement of the prescribers, change is unlikely to occur.<sup>1,2</sup> These comments should not divert our attention from the
Accuracy of Immunization Histories Provided by Adults Accompanying Preschool Children to a Pediatric Emergency Department
Authors: Karen P. Goldstein
Journal: JAMA (1993)

Because some have advocated the use of emergency departments to administer delayed childhood immunizations, we evaluated the accuracy of immunization histories obtained in this setting by comparison with medical records of inner-city health care facilities.Questionnaires were orally administered to adults accompanying children to the emergency department. Individual medical records were reviewed.Pediatric emergency department at Wyler Children's Hospital, University of Chicago and 68 inner-city primary care clinics.Children aged 3 to 65 months registering for medical care. Of the sample, 98% were African American; 75% were Medicaid recipients.Adults' knowledge of immunization histories, immunization cards, and medical records compared with American Academy of Pediatrics/Immunization Practices Advisory Committee recommendations.Of the accompanying adults, 64% stated that their child's general immunization status was "up-to-date"; 65% of these had clinic records confirming that status. Only 8% of specific regimens stated by these adults accurately matched those found in clinic records. Moreover, 45% of adults accompanying children at least 16 months and older provided inaccurate information regarding previous receipt of measles immunization.Information provided by accompanying adults (from recall or from immunization cards) is inadequate to determine accurately which preschoolers in the pediatric emergency department are delayed in immunizations.
Abstract 3791: Sulphoraphane inhibits STAT3 and its related genes in Du 145 cancer cells
Authors: Wonil Koh, Kwangseok Ahn, Soojin Jeong, Taerin Kwon, Jihyun kim, Jimin Shin, Sunmi Yun, Deokbeom Jung, Jihoon Jung, Eunok Lee, Hyojeong Lee, Hyojung Lee, Junxuan Lu, Sung Hoon Kim
Journal: Cancer Research (2010)

Abstract Sulforaphane is a naturally occurring isothiocyanate compound mainly found in cruciferous vegetables. Sulforaphane has demonstrated cancer chemopreventive activities in a number of organ sites, including prostate. Mechanistic investigations have shown that SFN induces caspase-mediated apoptosis that is mediated through a rapid intracellular ROS generation. Since STAT3 signaling is crucial for cancer cell survival and ROS has been linked to inactivation of this transcriptional factor, we hypothesized that STAT3 may be an important target for SFN. Here, we investigated the effect of sulforaphane on the regulation of STAT3 in association of ROS in Du145 prostate cancer cells. We first confirmed that sulforaphane induced apoptosis by activation of caspase 8, 9, and 3, PARP cleavage and increase of TUNEL positive cells in Du145 cells, which were preceded for many hours by the increase of intracellular ROS, peaking at 30 minutes of exposure. We demonstrate for the first time that sulforaphane suppressed constitutive STAT3 activation and DNA-binding of STAT3 in a time- and dose-dependent manner in Du145 cells. These actions were also found in U266 multiple myeloma cells and U937 lymphoma cells. In addition, sulforaphane down-regulated the expression of STAT3-related genes such as bcl-2, bcl-xL, survivin, cyclin D1, and VEGF in Du145 cells. Furthermore, sulforaphane cross-linked JAK2, the upstream kinase of STAT3, in a time- and dose-dependent manner. Thiol-reducing agent dithiothreitol (DTT) reversed the inactivation of STAT3 and JAK2 induced by sulforaphane. Interestingly, N-acetyl cysteine (NAC), which leads to increased intracellular GSH synthesis, reversed the molecular patterns of PARP cleavage and inactivation of JAK2 and STAT3 induced by sulphoraphane. Taken together, these findings suggest that sulforaphane exposure leads to a rapid generation of ROS in Du145 cells and inhibition of JAK2/STAT3 pathway, followed by caspase-mediated apoptosis. Our data suggest that the JAK2/STAT3 pathway may be a novel target of SFN contributing to apoptosis. 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 3791.
Diltiazem prevents hypertrophy progression, preserves systolic function, and normalises myocardial oxygen utilisation in the spontaneously hypertensive rat
Authors: J. F TUBAU, J. WIKMAN-COFFELT, B. M MASSIE, J. SZLACHCIC, W. W PARMLEY, R. SIEVERS, S. HENDERSON
Journal: Cardiovascular Research (1987)

The effects of diltiazem, a calcium channel blocker, and methyldopa, an adrenergic blocker, on left ventricular hypertrophy and left ventricular function were assessed in spontaneously hypertensive rats and Wistar-Kyoto controls. Diltiazem (30 mg.kg-1/day), methyldopa (400 mg.kg-1/day), or placebo were given with water for six months. Left ventricular function was studied in 12 month old animals using an isovolumetrically contracting heart preparation by measuring maximum developed pressure and myocardial oxygen consumption. Systolic blood pressure was reduced by both drugs but more so by methyldopa. Despite its lesser antihypertensive effect, diltiazem reduced heart to body weight ratios in the spontaneously hypertensive rat to a similar degree as methyldopa (3.4(0.2) and 3.4(0.1) compared with placebo 3.7(0.2), p less than 0.05). Maximum developed pressure increased with methyldopa and diltiazem compared with placebo (188(11) and 200(11) vs 166(11) mmHg, p less than 0.05). Myocardial oxygen consumption was lower in the spontaneously hypertensive rat receiving placebo than in the controls (22.8(3.2) vs 28.3(3.8) ml.min-1.100 g-1, p less than 0.05) and was significantly increased by diltiazem but not by methyldopa (27.9(0.4) vs 24.5(0.6) ml.min-1.100 g-1, p less than 0.05 and NS respectively vs the spontaneously hypertensive rat receiving placebo). Diltiazem and methyldopa normalised the isomyosin composition in the spontaneously hypertensive rat. Myocardial concentrations of energy related metabolites obtained at maximum developed pressure were not different between spontaneously hypertensive rats receiving placebo and controls. However, both diltiazem and methyldopa treated spontaneously hypertensive rats showed a significant reduction in adenosine triphosphate and phosphocreatine and a rise in inorganic phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)
Remarks on Dr. Kolle's Review of my Article--"Professor Kitasato's Anticholera Serum."
Authors: A. Nakagawa
Journal: BMJ (1897)

ANTICHOLERA SERUM1.a," 'L 337 tions, it must be accepted as a lamentable but unavoidable eequenee of the disease.Tthen, again, to us it seemed probable that the immediate re- sult of forcible rectification might be paralysis, or at least paresis, temporary or long continued; and arguing on the analogy of what has sometimes occui red after reposition of limbs subsequently to tuberculous arthritis, we felt it was possible that so novel a proceeding in the spine might by foltowed either by suppuration or by an acute dissemination of tubercle.But when we come to reflect on our experience in -dealing with a large number of these articular cases, we could not altogether recall more than three or four cases in which it could be distinctly affirmed that forcible rectification and acute dissemination of tubercle stood in the relationship of cause and effect.Nor has our combined experience been small.
Dynamics of insulin secretion and the clinical implications for obesity and diabetes
Authors: Susumu Seino, Tadao Shibasaki, Kohtaro Minami
Journal: Journal of Clinical Investigation (2011)

Insulin secretion is a highly dynamic process regulated by various factors including nutrients, hormones, and neuronal inputs. The dynamics of insulin secretion can be studied at different levels: the single β cell, pancreatic islet, whole pancreas, and the intact organism. Studies have begun to analyze cellular and molecular mechanisms underlying dynamics of insulin secretion. This review focuses on our current understanding of the dynamics of insulin secretion in vitro and in vivo and discusses their clinical relevance.
Studies of the receptor for phage A25 in group A streptococci: the role of peptidoglycan in reversible adsorption.
Authors: P P Cleary, L W Wannamaker, M Fisher, N Laible
Journal: The Journal of Experimental Medicine (1977)

Irreversible adsorption of a virulent phage, phage A25, to heat-killed streptococci, groups A, G, and A variant, has been achieved. Adsorption reflected the observed host range for phage A25 in that heat-killed group B cells were not able to inactivate the phage. Broken cells, cell walls, and peptidoglycan prepared from a group A strain K56 failed to adsorb the phage irreversibly, but retained the potential to carry out reversible adsorption. Experimental data including electron microscopy have demonstrated the specificity of reversible adsorption and have identified the peptidoglycan as a necessary cellular component of the receptor. The sensitivity of whole cells and purified peptidoglycan to muralytic enzymes suggests that the cell wall and peptidoglycan must be intact for optimal adsorption. In general the results are explained by postulating that adsorption of A25 phage particles to group A cells occurs by a two-step process; the first step involves recognition and reversible binding of the phage tail to the cell wall peptidoglycan, the second step is an irreversible reaction catalyzed by a yet unidentified cellular component which is destroyed when cells are ruptured.
Delta-9-Tetrahydrocannabinol in Cancer Chemotherapy: Research Problems and Issues
Authors: Michael P. Carey, Thomas G. Burish, Dean E. Brenner
Journal: Annals of Internal Medicine (1983)

A critical review of the literature assessing the antiemetic efficacy of delta-9-tetrahydrocannabinol (THC) in patients receiving cancer chemotherapy showed considerable inconsistency in results. The equivocal nature of these results partly reflects the difficulty of doing research on antiemetic therapies, but also can be attributed to differences in the adequacy and nature of the research designs, procedures, and assessment instruments that have been used. Several factors were also identified that are seldom studied but may be important in determining whether THC will be effective: patient variables, such as chemotherapy regimen and age; pharmacologic variables, such as drug tolerance, dose, schedule, toxicity, route of administration, and drug interactions; and environmental variables associated with administration setting. The need to differentiate pharmacologically induced from conditioned nausea and vomiting was also pointed out. We believe that THC does have antiemetic efficacy, but the lack of controlled research does not allow precise knowledge of its true effectiveness and toxicity. Well-controlled trials are needed to help answer some of these questions.
POLIOMYELITIS AS A COMPLEX INFECTION
Authors: Gilbert Dalldorf, Heribert Weigand
Journal: The Journal of Experimental Medicine (1958)

Young cynomolgus monkeys inoculated intracerebrally with an attenuated Type 1 polio virus and, after 5 days, with a monkey adapted Coxsackie A-14 virus frequently became paralyzed. Neither virus alone was capable of inducing paralysis. Similar results were observed when the AB IV strain of Coxsackie A-7 was substituted for the A-14 virus. In this case the 2nd inoculation was made intramuscularly. Paralytic poliomyelitis may at times represent the summation of two infections, the total of motor neuron destruction by two independent and noninterfering enteroviruses.
The Meal Test in Clinical Electrocardiography
Authors: ERNST SIMONSON, C. A. MCKINLAY
Journal: Circulation (1950)

The fact that all ordinary meal induces definite changes in the electrocardiogram suggested the possible utility of a meal test as a mild and convenient form of stress in clinical work. Comparison of normal persons and cardiac patients revealed frequent significant electrocardiographic differences in the response to a meal. This was especially notable in patients with proved or suspected coronary insufficiency. It appeared that the incidence of abnormal responses to the meal increased with the clinical degree of cardiac involvement The response of the T wave was most frequently aberrant in patients.
Blood Pressure in Intracerebral Hemorrhage — How Low Should We Go?
Authors: Jennifer A. Frontera
Journal: New England Journal of Medicine (2013)

Intracerebral hemorrhage is one of the most devastating forms of stroke. The median 1-month case fatality rate is 40%, and only 12 to 39% of patients achieve functional independence.1 Although previous trials of therapies for patients with this condition have not shown a benefit with respect to outcome,2,3 targeted blood-pressure management after an intracerebral hemorrhage has been both a promising and a contentious area of recent study. Early elevations of blood pressure are common after an intracerebral hemorrhage, and many have debated whether this response is adaptive (to maintain perfusion to an ischemic penumbra surrounding the hematoma) or potentially . . .
Premature senescence of T-cell subsets in axial spondyloarthritis
Authors: Johannes Fessler, Andrea Raicht, Rusmir Husic, Anja Ficjan, Christina Duftner, Wolfgang Schwinger, Christian Dejaco, Michael Schirmer
Journal: Annals of the Rheumatic Diseases (2015)

Objective To investigate the possible occurrence of early thymic failure and premature senescence of naïve and memory T-cells in patients with axial spondyloarthritis (aSpA). Methods Prospective, cross-sectional study of consecutive patients with aSpA (n=51), rheumatoid arthritis (RA, n=51) and healthy controls (HCs, n=50). Demographic, clinical and laboratory parameters were collected in all patients and we isolated naïve (CD45RA + ) and memory (CD45RO + ) CD4 + and CD8 + T-cell subsets by MACS technology. T-cell receptor rearrangement excision circle (TREC) and telomere length were measured by real-time PCR. We used TRECs as a surrogate for thymus function and telomere length as an indicator of cellular senescence. Telomerase activity was analysed with the Telomeric Repeat Amplification Protocols. Results We observed a premature decline of thymic output in patients with aSpA and patients with RA compared with HCs as indicated by a reduction of TREC levels in naive T-cells (aSpA: age adjusted regression coefficient (reg coeff ) for CD4 + CD45RA + T-cells −2.566, p=0.023; RA reg coeff =−2.844, p=0.008). Telomere length of all CD4 + and CD8 + T-cell subsets was reduced in young patients with aSpA compared with HCs, whereas data for patients with RA were comparable with HCs. Telomerase activity was inversely correlated with telomere length in HCs (correlation coefficient (cor coeff )=−0.532, p&lt;0.001) but not in patients with aSpA (cor coeff =−0.056, p=0.697) and RA (cor coeff =−0.003, p=0.982). Conclusions Our data indicate an age-inappropriate shrinkage of thymic output, an inappropriate shortening of telomeres in young patients with aSpA and an impaired telomerase enzyme in patients with aSpA and RA.
Pituitary Cytokine and Growth Factor Expression and Action
Authors: David Ray, Shlomo Melmed
Journal: Endocrine Reviews (1997)

The complex range of pituitary regulatory mechanisms reviewed here underlies the critical function of the pituitary in sustaining all higher life forms. Thus, the ultimate net secretion of pituitary hormones is determined by signal integration from all three tiers of pituitary control. It is clear from our current knowledge that the trophic hormone cells of the anterior pituitary are uniquely specialized to respond to these signals. Unravelling their diversity and complexity will shed light upon the normal function of the master gland. Understanding these control mechanisms will lead to novel diagnosis and therapy of disordered pituitary function (357).
An Address ON COMPRESSED AIR ILLNESS AND EXPERIMENTAL RESEARCH: Delivered before the Dublin Branch of the Medical Research Society, January 25th, 1912
Authors: L. E. Hill
Journal: BMJ (1912)

_B __9_ indeed a martyrology.In the last few years I have operated in almost all cases that have come to me, for I have felt that it was well worth the while of any patient to face the risk of operation rather than to suffer the agony which
Low hippocampal PI(4,5)P2 contributes to reduced cognition in old mice as a result of loss of MARCKS
Authors: Laura Trovò, Tariq Ahmed, Zsuzsanna Callaerts-Vegh, Andrea Buzzi, Claudia Bagni, Marinee Chuah, Thierry VandenDriessche, Rudi D'Hooge, Detlef Balschun, Carlos G Dotti
Journal: Nature Neuroscience (2013)
Gender differences in sleep disordered breathing in a community-based sample.
Authors: S Redline, K Kump, P V Tishler, I Browner, V Ferrette
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Gender differences in the relative frequency of sleep-disordered breathing (SDB) have been observed in surveys of patient groups referred for clinical evaluation compared with population surveys. In this study, we assessed the associations of gender, SDB, and symptoms of SDB in 389 participants (16 to 84 yr of age) in an ongoing genetic-epidemiologic study of sleep apnea. Subjects included index probands with laboratory-confirmed obstructive sleep apnea syndrome (laboratory sample, n = 36) and their family members and neighbors (the community sample). SDB was assessed with overnight in-home monitoring of airflow, oximetry, heart rate, and chest wall impedance, and symptoms were assessed with standardized questionnaires. In the entire sample, SDB, defined as a respiratory disturbance index [RDI] > or = 15, was more prevalent among males (38%) than among females (15%) (p < 0.05). Males predominated by a ratio of 8:1 in the laboratory sample (31 males, five females). In contrast, the proportion of males to females with SDB was only 2:1 in the community sample, in which an RDI > or = 15 was observed among 26% of males and 13% of females. In the laboratory sample, females tended to be younger and were significantly heavier than males. However, in the community sample, females with SDB were older than male apneic subjects (63.4 +/- 13.9 versus 47.2 +/- 15.6 years, mean +/- SD; p < 0.01), and included a majority of postmenopausal women (75%). No differences in body mass index were noted between males and females with SDB recruited from the community.(ABSTRACT TRUNCATED AT 250 WORDS)
Absence of branched chain acyl-transferase as a cause of maple syrup urine disease.
Authors: D J Danner, N Armstrong, S C Heffelfinger, E T Sewell, J H Priest, L J Elsas
Journal: Journal of Clinical Investigation (1985)

Decreased function of human mitochondrial branched chain alpha-ketoacid dehydrogenase complex results in branched chain ketoacidemia or maple syrup urine disease. Activity of this multienzyme complex varies from 0 to approximately 15% of wild type branched chain alpha-ketoacid dehydrogenase complex activity within the population of homozygous affected individuals. We used the technique of Western Blotting with antibodies against purified bovine liver branched chain alpha-ketoacid dehydrogenase complex to screen mitochondrial proteins from cultured human fibroblasts for immunocrossreactive proteins. This method probes the physical structure of the proteins forming this multienzyme complex. One patient with branched chain ketoacidemia lacked an immunoreactive transacylase protein. This protein catalyzes the transfer of the branched chain acyl group from the decarboxylase to reduced coenzyme A. Kinetic analysis of the enzyme activity in cell lysates from this patient confirmed that the complex would not utilize coenzyme A. Thus, we have defined a structural basis for an impaired multienzyme complex of mitochondria in man.