tbuckley/cabot-search huggingface dataset:
Regional Brain Morphometry and Impulsivity in Adolescents Following Prenatal Exposure to Cocaine and Tobacco
Authors: Jie Liu, Barry M. Lester, Nurunisa Neyzi, Stephen J. Sheinkopf, Luis Gracia, Minal Kekatpure, Barry E. Kosofsky
Journal: JAMA Pediatrics (2013)

Animal studies have suggested that prenatal cocaine exposure (PCE) deleteriously influences the developing nervous system, in part attributable to its site of action in blocking the function of monoamine reuptake transporters, increasing synaptic levels of serotonin and dopamine.To examine the brain morphologic features and associated impulsive behaviors in adolescents following prenatal exposure to cocaine and/or tobacco.Magnetic resonance imaging data and behavioral measures were collected from adolescents followed up longitudinally in the Maternal Lifestyle Study.A hospital-based research center.A total of 40 adolescent participants aged 13 to 15 years were recruited, 20 without PCE and 20 with PCE; a subset of each group additionally had tobacco exposure. Participants were selected and matched based on head circumference at birth, gestational age, maternal alcohol use, age, sex, race/ethnicity, IQ, family poverty, and socioeconomic status.Subcortical volumetric measures of the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens; cortical thickness measures of the dorsolateral prefrontal cortex and ventral medial prefrontal cortex; and impulsivity assessed by Conners' Continuous Performance Test and the Sensation Seeking Scale for Children.After controlling for covariates, cortical thickness of the right dorsolateral prefrontal cortex was significantly thinner in adolescents following PCE (P = .03), whereas the pallidum volume was smaller in adolescents following prenatal tobacco exposure (P = .03). Impulsivity was correlated with thalamic volume following either PCE (P = .05) or prenatal tobacco exposure (P = .04).Prenatal cocaine or tobacco exposure can differentially affect structural brain maturation during adolescence and underlie enhanced susceptibility to impulsivity. Additional studies with larger sample sizes are warranted.
INTESTINAL ANTISEPSIS IN SURGERY
Authors: Edgar J. Poth
Journal: JAMA (1953)

The modern concepts of intestinal antisepsis have developed during the past 12 years. Initially, certain sulfonamides, which were poorly absorbed from the gastrointestinal tract, were found to act locally to alter the bacterial flora. These compounds had relatively narrow antimicrobial spectrums, had little effect against the gram-positive organisms, and acted primarily as bacteriostatic agents against the gram-negative bacteria found in the gastrointestinal tract of man. While many of the sulfonamides have some activity, it was not until succinylsulfathiazole (Sulfasuxidine) was used by Knotts, Lee, Inui and myself<sup>1</sup>that the gram-negative flora of the bowel could be altered significantly and consistently. Many sulfonamides were investigated, but ultimately only three could be used as practical intestinal antiseptics. They were, in the order discovered, succinylsulfathiazole,<sup>2</sup>phthalylsulfathiazole (Sulfathalidine),<sup>3</sup>and phthalylsulfacetamide (Thalamyd).<sup>4</sup>Of these three, succinylsulfathiazole was the most promising and satisfactory, because it not only altered the gram-negative flora of
Vasopeptidase inhibition prevents nephropathy in Zucker diabetic fatty rats
Authors: S SCHAFER
Journal: Cardiovascular Research (2003)

Blocking the renin-angiotensin system is an established therapeutic principle in diabetic nephropathy. We investigated whether inhibition of both neutral endopeptidase and ACE (vasopeptidase inhibition) can prevent functional and morphological features of nephropathy in the Zucker diabetic fatty (ZDF) rat, an animal model of type II diabetes.Homozygous (fa/fa) ZDF rats (each n=15) aged 10 weeks were treated with placebo, ramipril (1 mg/kg/day in drinking water), or the vasopeptidase inhibitor AVE7688 (45 mg/kg/day in chow). Metabolic parameters and renal function (metabolic cages) were assessed at baseline (age 10 weeks), and at age 17, 27, and 37 weeks. Twenty heterozygous animals (fa/-) served as lean, nondiabetic controls. At age 37 weeks, the animals were sacrificed and the kidneys analyzed histopathologically.Overt diabetes mellitus (blood glucose >20 mmol/l) was established at age 17 weeks in all homozygous ZDF rats. In the placebo group, urinary protein excretion increased progressively from 8+/-1 (baseline) to 342+/-56 mg/kg/day (week 37) whereas diabetes and proteinuria were absent in the lean control group. Ramipril tended to reduce albuminuria and morphological damage (p=ns) but AVE7688 virtually prevented albuminuria (33+/-12 mg/kg/day, p<0.05 vs. ZDF placebo) and drastically reduced the incidence and severity of glomerulosclerosis and tubulointerstitial damage.In ZDF rats, development of diabetes mellitus is accompanied by functional and morphological kidney damage that resembles human diabetic nephropathy. Diabetic nephropathy can be prevented by chronic vasopeptidase inhibition.
Receptor guanylyl cyclases.
Authors: S K Wong, D L Garbers
Journal: Journal of Clinical Investigation (1992)

Three different guanylyl cyclase cell receptors are known, but others will likely be discovered within the next few years. The general function of these receptors appear to relate to the regulation of fluid volume or fluid movement. New receptors, or possibly the currently known receptors, therefore, may be discovered in areas of the body where fluid volume regulation is important. Such fluids whose volume or composition might be regulated by guanylyl cyclase receptors include synovial fluid, uterine/oviductal luminal fluid, follicular fluid, aqueous humor, cerebral spinal fluid, seminiferous tubule luminal fluid, epididymal luminal fluid, seminal plasma, and airway luminal fluid. The function of the heterodimeric forms of guanylyl cyclase appear to relate to a primary regulation of nitric oxide (or similar molecules) concentrations, which are in turn regulated by a Ca2+/calmodulin-sensitive nitric oxide synthase.
Different functions of the platelet-derived growth factor-alpha and -beta receptors for the migration and proliferation of cultured baboon smooth muscle cells.
Authors: N Koyama, C E Hart, A W Clowes
Journal: Circulation Research (1994)

Migration of medial smooth muscle cells (SMCs) and their proliferation in the intima contribute to thickening of injured and atherosclerotic vessels. These events have been proposed to be regulated in part by platelet-derived growth factor (PDGF). Two separate PDGF receptors have been identified, PDGF-R alpha and PDGF-R beta. To study the functions of PDGF-R alpha and PDGF-R beta in vascular SMCs, neutralizing monoclonal antibodies (mAbs) specific for each of the two receptors were used. These antibodies allowed us to evaluate the role of each receptor for PDGF-induced proliferation and migration of cultured baboon SMCs. Both PDGF-AA and PDGF-BB stimulated SMC growth, with PDGF-BB being more potent than PDGF-AA. Studies with anti-PDGF-R alpha and anti-PDGF-R beta mAbs revealed that both PDGF receptors promoted the stimulatory signals for proliferation. In contrast, PDGF-BB stimulated SMC migration, whereas PDGF-AA had no stimulatory activity on its own. Additionally, PDGF-AA was able to suppress migration induced by PDGF-BB or fibronectin in modified Boyden's chamber assay. When PDGF-BB-induced migration was separated into chemotactic and chemokinetic activities, only the chemotactic component was inhibited by PDGF-AA. The suppression of SMC migration by PDGF-AA was eliminated by anti-PDGF-R alpha mAb. In addition, PDGF-BB, in the presence of anti-PDGF-R beta, bound only to PDGF-R alpha and caused suppression of SMC migration induced by fibronectin. These results suggest that when activated by ligand binding, both PDGF-R alpha and PDGF-R beta stimulate proliferation. In contrast, only activation of PDGF-R beta stimulates migration, whereas ligand binding to PDGF-R alpha leads to inhibition of cell migration. These observations provide support for the conclusion that PDGF-R alpha and PDGF-R beta may play different roles in SMC function and may be involved in different regulatory mechanisms during vascular remodeling.
Persistence of natural mineral fibers in human lungs: an overview.
Authors: A Churg, J L Wright
Journal: Environmental Health Perspectives (1994)

Virtually all available data on persistence of naturally occurring mineral fibers in human lungs have been derived from studies of asbestos fiber loads. These studies indicate that, although both amphibole and chrysotile asbestos fibers are found in the lungs of the general population and exposed workers, amphibole fibers are universally present in disproportionately large and chrysotile fibers in disproportionately small amounts compared to their known abundance in the original inhaled dusts. Why this should be remains unclear. Most reports have shown that fiber accumulation is proportional to measured exposure for amphiboles, but this is not generally true for chrysotile. Very little information is available on actual fiber clearance rates from human lungs. For amosite and crocidolite, estimated clearance half-times are measured in years to decades, whereas for chrysotile the available, rather indirect, data suggest that the vast majority of fibers are cleared within months, although some fibers may be sequestered and very slowly cleared. Overall these studies suggest that the differences between amphibole and chrysotile fiber burdens in man reflect much faster clearance of chrysotile fibers, rather than a failure of chrysotile deposition. A variety of other naturally occurring fibers are commonly found in human lungs, but there are no data on their rates of accumulation or disappearance.
Abstract 2957: Mutations of Cyclin D1 / beta-catenin are coexistent with mutations in Ras-PI3K pathway genes in endometrial cancer
Authors: Yuji Ikeda, Katsutoshi Oda, Shunsuke Nakagawa, Keiko Shoji, Tomoko Kashiyama, Shumpei Ishikawa, Shogo Yamamoto, Michihiro Tanikawa, Osamu Hiraike, Hiroyuki Aburatani, Tetsu Yano, Yuji Taketani
Journal: Cancer Research (2011)

Abstract Introduction: Mutant beta-catenin is translocated to nucleus, and induces Cyclin D1 expression. Cyclin D1 cooperates with CDK4/6 to accelerate cell cycle from G1 to S phase. In addition to canonical Wnt signaling pathway, beta-catenin is regulated by GSK-3beta, which is phosphorylated and downregulated by Akt. Endometrial carcinoma is the only tumor type, in which CyclinD1 mutations have been reported. Mutations of beta-catenin and Ras-PI3K pathway genes (such as K-Ras, PTEN and PIK3CA) are also well-known in endometrial cancer. In this study, we analyzed alterations of Cyclin D1 and beta-catenin, and addressed the relationship between these alterations and the Ras-PI3K activating mutations in endometrial cancer. Materials and methods: We extracted DNA from 91 primary endometrial carcinomas (under informed consent) and 13 endometrial carcinoma cell lines. Mutations of CCND1 (Cyclin D1), CTNNB1 (beta-catenin), K-Ras, PTEN and PIK3CA were analyzed by PCR-direct sequencing. In 24 cliniclal samples, Single Nucleotide Polymorphism (SNP) typing arrays (50K) were performed to evaluate copy number alterations in 11q13.3 for CCND1, 3p22.1 for CTNNB1, 12p12.1 for K-Ras, 10q23.3 for PTEN and 3q26.3 for PIK3CA. Result: Alterations of Cyclin D1 were detected in three clinical samples; mutations in two (2%) and amplification in one (4%) samples. Mutations of beta-catenin were detected in nine clinical samples (10%) and four cell lines (31%). No overlapping alterations were observed in Cyclin D1 and beta catenin. All the tumors with alterations in Cyclin D1 or beta-catenin coexist with mutations in the Ras-PI3K pathway genes (K-Ras, PTEN and PIK3CA). All the three patients with Cyclin D1 alterations were poor prognostic, whereas all the nine patients with beta-catenin mutations were alive without recurrence. Conclusion: Our data suggest that tumors with mutations in beta-catenin or Cyclin D1 could more efficiently accelerate cell cycle by cooperating with the coexistent alterations in the Ras-PI3K pathway genes. Furthermore, Cyclin D1 mutation might be associated with tumor aggressiveness and poor prognosis in endometrial cancer. 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 2957. doi:10.1158/1538-7445.AM2011-2957
An epidemiological method applied to practices to measure the representativeness of their prescribing characteristics.
Authors: D M Fleming
Journal: BMJ (1984)

The standardised report of the Prescription Pricing Authority, which is concerned with the prescribing characteristics of practices, was used as an epidemiological tool to evaluate the prescribing representativeness of practices. Study practices were compared with average prescribing results from family practitioner committees, which are specific for the geographical district and month sampled. The method was applied in 40 practices, representing 120 doctors who had been recruited to the third morbidity study in general practice. In these practices 488 items per 1000 people had been prescribed compared with 548 items per 1000 people from the matched values of family practitioner committees. There was a parallel reduction in the net ingredient cost of items per 1000 people--1414 pounds for the practices compared with 1600 pounds for the family practitioner committees. These differences were highly significant. The average net ingredient cost was the same for both groups. Study practices were biased towards reduced prescribing costs for drugs used to treat infections, respiratory diseases, disorders of the nervous system, skin disease, rheumatic disorders, and gastrointestinal problems. The comparison and its interpretation provide a model that may be used by individual practices to evaluate their own prescribing reports.
Hyposensitisation with house dust mite vaccine in bronchial asthma.
Authors: J O Warner, J F Price
Journal: BMJ (1976)

prescribed, as "we are already too far down that path to turn back."In "an issue in which there is more emotion than reason" we would make a plea for continued evaluation of therapy.If acceptable studies do not provide evidence of the superiority of oestrogens over placebo then we should stop prescribing them.
Fluvastatin, a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor, Attenuates Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction
Authors: Shunji Hayashidani, Hiroyuki Tsutsui, Tetsuya Shiomi, Nobuhiro Suematsu, Shintaro Kinugawa, Tomomi Ide, Jing Wen, Akira Takeshita
Journal: Circulation (2002)

Background — Short-term administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, has been shown to attenuate ischemia-reperfusion injury. However, the effects of long-term administration of statins on left ventricular (LV) remodeling and failure after myocardial infarction remain unknown. Methods and Results — Mice were subjected to coronary artery ligation and were treated for 4 weeks with vehicle or fluvastatin (10 mg/kg per day PO). Fluvastatin increased survival (61% versus 86%; P &lt;0.05) without affecting the infarct size (52±2% versus 49±3%; P =NS). Fluvastatin not only attenuated LV dilatation but also decreased LV end-diastolic pressure and lung weight. Furthermore, it reduced cardiac myocyte hypertrophy and interstitial fibrosis of the noninfarcted LV and also improved LV ejection performance. LV matrix metalloproteinase (MMP)-2 and MMP-13 were increased in myocardial infarction, which was attenuated in fluvastatin-treated mice. Conclusions — Fluvastatin increased survival in a murine model of postinfarct heart failure, which was associated with the amelioration of LV structural remodeling and contractile failure. Moreover, these effects were associated with the attenuation of increased MMP activity. Thus, long-term treatment with fluvastatin might be beneficial also in patients with heart failure and might improve their long-term survival.
Overview of New Technologies for Lower Extremity Revascularization
Authors: Jason H. Rogers, John R. Laird
Journal: Circulation (2007)

Lower extremity peripheral arterial occlusive disease poses a unique challenge to traditional angioplasty-based endovascular therapies. The diffuse nature of lower extremity atherosclerotic disease, the presence of chronic total occlusions, poor distal runoff, and the presence of critical limb ischemia all have contributed to the disappointing results of balloon angioplasty for complex infrainguinal arterial disease. These challenges have spawned the development of a host of new technologies in an attempt to improve the safety and effectiveness of percutaneous revascularization for lower extremity peripheral arterial occlusive disease. This review summarizes the recent advances in available technologies, including novel angioplasty balloons; nitinol stents, stent grafts, and drug-eluting stents; excisional, laser, and rotational atherectomy devices; devices for crossing total occlusions; true-lumen reentry devices; thrombectomy catheters; and embolic protection devices.
Editorial: Relicensure and recertification
Authors: M. L. Herns
Journal: JAMA (1974)

A commitment to the maintenance of professional competence by a continuing educational process is nothing new to medicine. It has been the motivating force for the formation of professional societies including the American Medical Association, for the launching of an imposing number of professional journals as well as the development of postgraduate programs, both by professional societies and by educational institutions. The attendance at meetings, continuing education courses, and refresher seminars all indicate wide interest by many practitioners in remaining currently informed about new developments in medicine. Individual motivation has been augmented by organizational requirements for participation in postgraduate training. The first such program was launched by the American Academy of General Practice (now the American Academy of Family Practice). More recently, nine state medical associations have adopted systems requiring the acquisition of educational credits as a condition for continued membership. Other encouragement has been offered by such accolades as
Mass B.C.G. Vaccination in Malta
Authors: V. Zammit-Tabona
Journal: BMJ (1952)

Between March and June 1950, a Norwegian medical team, together with four Maltese medical teams (which the Norwegians trained), carried out a survey of the tuberculin reaction of the section of the population of Malta aged 1-18 years, and vaccinated with B.C.G. the " negative " reactors.The campaign, the first of its kind in Malta, was held on an entirely voluntary basis, and wa § carried out under the auspices of the I.T.C. under the direction of Dr. A. Weidemann, of Norway, and myself.The tuberculin and B.C.G. vaccine used were prepared at the State Serum Institute in Copen- hagen; while the costs were borne mainly by the I.T.C. but in part also by the Government of Malta.Altogether 48,319 children and youths aged 1-18 years came for testing.The result of 42,986 of these tests is known, while 36,320 were vaccinated with B.C.G.Of 6,009 persons over 18 years who were tuberculin- tested, 2,361 were vaccinated during the campaign.This report also includes the results obtained in this group.
T.V. Programme on Heart Disease
Authors: E. Ll. Lloyd
Journal: BMJ (1974)

Basal 2 4 6 80.01 2 4 6 80-1 Heart rate (beats/min) Tremor (relative amplitude) 120 5-1 " ~~B 0.01 0-1 B 001 0.1 L-Isoprenaline sulphate (uqg/kq/min) ( loq scale)Effects of increasing intravenous doses of isoprenaline in eight patients with obstructive lung disease not previously treated with adrenergic betastimulating drugs (I) and effects after one, two, and three months' treatment with terbutaline (II, III, and IV).end of the first isoprenaline infusion.This was much less pronounced after one, two, and three months' terbutaline treatment.The rise in pulse rate was also somewhat less during treatment.From these preliminary findings it seems that resistance does not develop in the bronchial muscles after this dose of terbutaline, while there is an obvious development of resistance to isoprenaline-induced muscular tremor.This accords with clinical experience.We shall observe further isoprenaline dose-response curves after six, nine, and 12 months' treatment with terbu- taline to avoid seasonal variations in bronchial obstruction and finally after giving terbutaline in very large doses for several days.
Parental diabetes and birth weight of offspring: intergenerational cohort study
Authors: E. Hypponen
Journal: BMJ (2003)

According to the fetal insulin hypothesis, shared genetic factors lead to suboptimal prenatal growth and to insulin resistance in the parent's later life. 1 If this is true, we expect non-insulin dependent diabetes in parents to be associated with lower birth weight among their offspring.Some evidence supports an inverse association between birth weight of offspring and paternal diabetes. 2 3The association between fetal macrosomia and a mother's diabetes during pregnancy has been established, 4 however this is likely to be caused by acute metabolic effects.We used data from the large cohort study of British births in 1958 to evaluate whether a father's non-insulin dependent diabetes or a mother's diabetes starting after childbirth is associated with the birth weight of their offspring.
Abstract 2090: Mutational analysis in circulating tumor cells (CTC):ScreenCell MB Filtration Unit and ICE COLD-PCR
Authors: Katherine A. Richardson, Grant Wu, Yanan Kuang, Lilin Wang, Benjamin Legendre, Rui Lin, Yanggu Shi, Phil Eastlake, Yvon Cayre, Pasi Janne, Robert Distel
Journal: Cancer Research (2012)

Abstract The aim of this study was to validate the use of the ScreenCell® MB Filtration Unit for detection of mutations in Circulating Tumor Cells. This device allows physicians to easily isolate any CTCs using a simple blood draw which can be performed at a local doctor's office. This is especially important when trying to analyze CTCs in elderly patient populations and in regions where the large medical centers are far away. Once isolated, the filter containing the CTCs can be sent to a laboratory for DNA isolation and the mutation analysis. Mutational analysis using ICE COLD-PCR can then be performed without the use of expensive or specialized equipment. The mutation was characterized using standard Sanger DNA sequencing with a detection limit of 0.5 - 0.1% mutant sequence in the wild-type background. Results will be presented from a mock experiment where PC9 cells (EGFR exon 19 deletion: p.E746_A750del) or H1975 cells (EGFR exon 21: p.L858R) were spiked into blood and then these mock CTCs were collected on the ScreenCell Molecular Filter Device. Following DNA isolation, the mutations were easily detected at the lowest number of cells spiked in to the blood samples (10 cells). Additional data from CTCs collected from NSCLC patients detected the L858R point mutation, an exon 19 E746_A750del mutation, and an exon 19 E746_S752delinsV. Mutations in these same samples could not be detected in DNA sequencing following standard PCR amplification. These data show that the ScreenCell MB Filtration Unit coupled to mutational analysis using ICE COLD-PCR can be an easy, cost-effective method for collection and analysis of CTCs in patient blood samples. Moreover, the device is simple enough to be used in any doctor's office. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2090. doi:1538-7445.AM2012-2090