tbuckley/cabot-search huggingface dataset:
Strong Asymmetric Mutation Bias in Endosymbiont Genomes Coincide with Loss of Genes for Replication Restart Pathways
Authors: Lisa Klasson, Siv G. E. Andersson
Journal: Molecular Biology and Evolution (2006)

A large majority of bacterial genomes show strand asymmetry, such that G and T preferentially accumulate on the leading strand. The mechanisms are unknown, but cytosine deaminations are thought to play an important role. Here, we have examined DNA strand asymmetry in three strains of the aphid endosymbiont Buchnera aphidicola. These are phylogenetically related, have similar genomic GC contents, and conserved gene order structures, yet B. aphidicola (Bp) shows a fourfold higher replication-induced strand bias than B. aphidicola (Sg) and (Ap). We rule out an increase in the overall substitution frequency as the major cause of the stronger strand bias in B. aphidicola (Bp). Instead, the results suggest that the higher GC skew in this species is caused by a different spectrum of mutations, including a relatively higher frequency of C to T mutations on the leading strand and/or of G to A mutations on the lagging strand. A comparative analysis of 20 γ-proteobacterial genomes revealed that endosymbiont genomes lacking recA and other genes involved in replication restart processes, such as priA, which codes for primosomal helicase PriA, displayed the strongest strand bias. We hypothesize that cytosine deaminations accumulate during single-strand exposure at arrested replication forks and that inefficient restart mechanisms may lead to high DNA strand asymmetry in bacterial genomes.
Disruption of tissue-type plasminogen activator gene in mice reduces renal interstitial fibrosis in obstructive nephropathy
Authors: Junwei Yang, Ryan W. Shultz, Wendy M. Mars, Rodney E. Wegner, Yingjian Li, Chunsun Dai, Kari Nejak, Youhua Liu
Journal: Journal of Clinical Investigation (2002)

Tissue-type plasminogen activator (tPA) is one of the major components in the matrix proteolytic network whose role in the pathogenesis of renal interstitial fibrosis remains largely unknown. Here, we demonstrate that ablation of tPA attenuated renal interstitial fibrotic lesions in obstructive nephropathy. Mice lacking tPA developed less morphological injury and displayed a reduced deposition of interstitial collagen III and fibronectin as well as total tissue collagen in the kidneys after sustained ureteral obstruction, when compared with their wild-type counterparts. Deficiency of tPA selectively blocked tubular epithelial-to-myofibroblast transition (EMT), but did not affect myofibroblastic activation from interstitial fibroblasts. A marked decrease in matrix metalloproteinase-9 (MMP-9) induction was found in the obstructed kidneys of tPA–/– mice, which led to a dramatic preservation of the structural and functional integrity of tubular basement membrane (TBM). In vitro, tPA induced MMP-9 gene expression and protein secretion in renal interstitial fibroblasts. Thus, increased tPA is detrimental in renal interstitial fibrogenesis through a cascade of events that lead to MMP-9 induction, TBM destruction, and promotion of EMT. Our findings establish a crucial and definite importance of EMT in the pathogenesis of renal interstitial fibrosis at the whole-animal level.
Intracellular ABC transporter A3 confers multidrug resistance in leukemia cells by lysosomal drug sequestration
Authors: B Chapuy, R Koch, U Radunski, S Corsham, N Cheong, N Inagaki, N Ban, D Wenzel, D Reinhardt, A Zapf, S Schweyer, F Kosari, W Klapper, L Truemper, G G Wulf
Journal: Leukemia (2008)
ENTEROSPASM SIMULATING GALLBLADDER DISEASE
Authors: None ZACHARY
Journal: JAMA (1924)

Medical literature is full of reports and discussions on the frequency of missed diagnoses of cholelithiasis and cholecystitis. It is only lately that we have learned to recognize gallbladder affections long before the typical syndrome has developed, and every one is eager to report cases that remained unrecognized for a number of years. It is fruitless, however, to search the literature for reported instances in which the diagnosis of gallbladder disease was made, though none existed. This, perhaps, can be explained by the fact that, unless the case comes to the operating table or to necropsy, it is very difficult to disprove that a gallbladder condition was really present. It used to be a matter of considerable amazement to us to find many more cases of gallstones and definitely pathologic gallbladders in the dissecting room and at necropsy than was ever suspected during life. Today, the frequency of missed diagnoses
2-Chloro-2′-deoxyadenosine inhibits DNA repair synthesis and potentiates UVC cytotoxicity in chronic lymphocytic leukemia B lymphocytes
Authors: E Van Den Neste, S Cardoen, B Husson, J-F Rosier, A Delacauw, A Ferrant, G Van den Berghe, F Bontemps
Journal: Leukemia (2002)
Is anaesthetist dentist's agent?
Authors: A. M. Danziger
Journal: BMJ (1967)

JBOURff recognized sense.The criteria of Tow and Cheng for hysterectomy, applied to our series, twould result in fewer hysterectomies being performed.Hysterectomy should be reserved, as they themselves assert, for selected cases and not used in childless women who do not need it or in patients with advanced disease ,who die as a consequence of it.Far more important than a contrived argument about hysterectomy is the problem ,of ensuring the effective follow-up of all mole cases, so that patients who need treatment receive it before the chance of recovery is lost.Patients still die because the follow- -up methods available are inadequate or not even used.A reliable centralized follow-up system could now be devised with the technology available in the United King- 4om.There is a case for making hydatidiform mole a notifiable disease.-Iam, etc., ,Fulham Hospital, K. D. BAGSHAWE.London W.6.Trephine Biopsy of the Lung SIR,-
Expert attacks decision in US to stop use of bevacizumab for eye condition
Authors: N. Hawkes
Journal: BMJ (2011)

A decision by the US Department of Veterans Affairs to stop using the anticancer drug bevacizumab (marketed as Avastin) to treat wet age related macular degeneration after reports of infections apparently caused by contaminated syringes was criticised as unnecessary by a leading specialist in the eye disease.

Bevacizumab is unlicensed in the United States for treating age related macular degeneration but has been widely used because it is much cheaper and has the same mode of action as the licensed drug ranibizumab (Lucentis). At the end of August the US Food and Drug Administration reported a cluster of infections in the Miami area linked to a pharmacy in Hollywood, Florida, which had repackaged bevacizumab into syringes suitable for injection into the eye.

Patients from two Veterans Affairs hospitals—one in Nashville, Tennessee, and the other in the San Fernando valley, Los Angeles—are also reported to have become infected after injections of bevacizumab. Many lost their remaining sight; and the family of one man treated in …
A DEPARTMENT OF PHYSICAL THERAPY
Authors: NORMAN E. TITUS
Journal: JAMA (1926)

Beekman Street Hospital was reorganized in the spring of 1924. When the new staff decided to devote more attention to the care of industrial patients, it was believed necessary that they should receive physical therapy. I was asked to organize and take charge of the new department. The original space allotted for the department was about 1,100 square feet, and this was sufficient for about nine months, when plans had to be made to enlarge it. At present even the new department of 1,900 square feet is proving to be too small. When space is considered in planning a department of physical therapy, it always would be wise to make the minimum 2,000 square feet, even in a small hospital of 100 beds. It is particularly difficult to expand a department, as the wiring and arrangement of apparatus should be planned originally to last for a long time. The apparatus
934. Initial Results of the Treatment of a Cardiomyopathy in Myopathic Hamsters by IGF-1 Based on Plasmid DNA Gene Transfer
Authors: Armelle Serose, André Salmon, Marc Y. Fiszman, Yves Y. Fromes
Journal: Molecular Therapy (2005)

Dilated cardiomyopathies (DCM) are due to progressive dilatation of the cardiac cavities and thinning of the ventricular walls and lead unavoidably to heart failure. They remain a major cause for heart transplantation; therefore, obtaining efficient treatments for DCM remains a challenge. We have taken advantage of the hamster strain CHF147 that displays a progressive cardiomyopathy leading to heart failure in order to test whether stimulation of a hypertrophic response could delay the process of dilatation. Six month-old CHF147 hamsters were treated with recombinant IGF-1 at low dose and for a limited time. We analyzed structure and function of the cardiac muscle at 5 weeks after initiation of the treatment. Our previous results have validated the use of recombinant IGF-1 protein (rIGF-1). However, as systemic administration of IGF-1 protein may lead of extra-cardiac side effects, we have tested the efficiency of direct intramyocardial injections of a plasmid DNA containing an IGF-1 coding cDNA (pIGF1) and we compared this new approach to the efficacy of systemic administration of rIGF-1.
A STUDY WITH NORETHANDROLONE (NILEVAR) IN A MENTAL HOSPITAL ON PATIENTS WITH BOWEL AND BLADDER INCONTINENCE
Authors: SOL SHERMAN
Journal: American Journal of Psychiatry (1960)

Norethandrolone was effective in controlling bowel and bladder incontinence in 10 of 13 patients who had been hospitalized for periods of from 6 months to 29 years. The most severely incontinent patients at the hospital were chosen for this study. Upon conclusion of the study the improvement in 6 patients was excellent, in 1 good, in 3 fair improvement, in 2 it was unchanged, and one patient was dropped from the study because he refused to take the medication. A daily dose of 30 mg. by mouth was effective in most instances. No side effects were noted at any time during norethandrolone therapy. The mechanism by which norethandrolone exerts its anabolic action is not fully understood, and further studies in this area are planned. The results of this study are in agreement with those of Vaisberg and his co-workers and Vlavianos and his associates.
Analysis of the Electrocardiograms Obtained from 1000 Young Healthy Aviators
Authors: JOHN M. PACKARD, JOHN S. GRAETTINGER, ASHTON GRAYBIEL
Journal: Circulation (1954)

Ninety-six per cent of the original subjects were traced after a period of 10 to 12 years; 202 were dead, and data obtained on re-examination were complete for 639. Except in one case of myocardial infarction, subjects with "borderline" or frank electrocardiographic abnormalities showed no symptoms of the development of heart disease. It is argued that the borderline abnormalities, considered as a group, must have little pathologic significance; otherwise, out of the relatively large number of subjects in this group, some would have exhibited symptoms. Although heart disease did not develop in any of the subjects with frank electrocardiographic abnormalities, such as bundle-branch block, the same argument does not hold with equal force because of the small number of cases in that group.
The Patient With Multiple Alloantibodies
Authors: Peter D. Issitt
Journal: JAMA (1982)

<h3>To the Editor.—</h3> A recent report by Patten and Conti inThe Journal(1982;247:209) described collection of 10 units of blood in a 17-week period from a woman who was said to be the only compatible donor for the patient, her sister. The data given leave doubts as to whether the heroic efforts on the part of the donor were really necessary. First, a week after infusion of 3 units of blood, the patient suffered a delayed hemolytic transfusion reaction. Her serum was found to contain anti-C, anti-E, anti-Jk<sup>b</sup>and an antibody of "uncertain specificity" that reacted with an antigen of high incidence. This last antibody was believed to be the "most likely cause" of the reaction, but no data on which this conclusion was based are given. Did the anti-Jk<sup>b</sup>play any role in the reaction? Antibodies in the Kidd system have many times caused delayed transfusion
Polymyxin B and Colistin
Authors: Nathaniel M. Nord, Paul D. Hoeprich
Journal: New England Journal of Medicine (1964)

GRAM-negative bacilli, in particular pseudomonas species, are of increasing concern to the clinician as infectious and therapeutic problems.1 , 2 Accordingly, polymyxin B has grown to singular importance as its utility to the treatment of systemic infections caused by pseudomonas species has been appreciated and exploited.In 1961 colistin was introduced as an agent that supposedly retained the antibacterial merit of polymyxin B in a polypeptide compound of lesser inherent nephrotoxic liability. From the outset, the striking pharmacologic and chemical similarities of colistin to the entire polymyxin group of antibiotics, including polymyxin B, were recognized.3 4 5 6 However, critical comparison of these agents, taking . . .
The role of structure in the disposition of halogenated aromatic xenobiotics.
Authors: L S Birnbaum
Journal: Environmental Health Perspectives (1985)

Halogenated aromatic xenobiotics such as the chlorinated and brominated biphenyls, naphthalenes, dibenzodioxins, and dibenzofurans are widespread environmental contaminants. The number, position, and nature of the halogen atoms as well as the structure of the aromatic rings influence the disposition of these chemicals in living systems. Absorption is governed primarily by the physical properties of lipophilicity and solubility. Distribution through the blood occurs by nonspecific binding to plasma proteins and cellular components. Liver and adipose tissue are the major depots. Metabolism is a prerequisite for excretion. The highly substituted isomers tend to be resistant to metabolism. The route of excretion shifts from urine to feces with increasing size and number of halogen atoms. Although pharmacokinetic modeling has allowed some predictions to be made from one compound to another or across species, more information on metabolism is required in order to improve the ability to predict the disposition in humans of this class of toxic environmental pollutants.
The Effects of 5-Lipoxygenase Inhibition by Zileuton on Platelet-activating-factor-induced Pulmonary Abnormalities in Mild Asthma
Authors: FEDERICO P. GÓMEZ, RAQUEL IGLESIA, JOSEP ROCA, JOAN A. BARBERÁ, K. FAN CHUNG, ROBERT RODRIGUEZ-ROISIN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Platelet-activating factor (PAF) has been implicated in the pathogenesis of asthma. We investigated whether PAF-induced neutropenia and lung function disturbances are secondary to activation of the 5-lipoxygenase (5-LO) pathway with the consequent liberation of leukotrienes. The effect of a selective 5-LO inhibitor (zileuton) was examined in 10 mildly asthmatic patients (24 ± 1 [mean ± SE] yr; FEV1 = 94 ± 4% predicted) before and after PAF inhalation, in a randomized, double-blind, placebo-controlled, crossover fashion. Patients were studied at baseline, 3 h after an oral single dose of zileuton (600 mg) or placebo, and then at 5 min, 15 min, and 45 min after PAF (18 μ g) inhalation. Compared with vehicle, premedication with zileuton reduced both PAF-induced neutropenia at 5 min (by 43%) (p < 0.005) and the subsequent rebound neutrophilia at 15 min and 45 min (by 50% and 47%, respectively) (p < 0.025 each). In addition, at 5 min after PAF inhalation, zileuton attenuated increases in respiratory system resistance (Rrs) (by 39%) (p < 0.01) and in the alveolar–arterial Po 2 difference (A–a)Po 2 (by 40%) (p < 0.05), and the decrease in PaO2 (by 27%) (p < 0.005). The protective effect of zileuton against PAF-induced ventilation–perfusion (V˙ a/Q˙) defects was shown by a parallel improvement (decrease) in an overall marker of V˙ a/Q˙ inequality (dispersion of retention minus excretion of inert gases corrected for dead space; DISP R-E *) (by 43%) 5 min after administration of PAF (p < 0.01). These findings indicate that PAF-induced systemic and pulmonary effects in patients with mild asthma are effectively mediated by the ongoing release of leukotrienes.
EXPERIMENTALLY PRODUCED GENUINE EPITHELIAL METAPLASIA IN THE STOMACHAND THE RELATIONS OF EPITHELIAL METAPLASIA TO CARCINOMA, AS DEMONSTRATED BY CASES REPORTED IN THE LITERATURE.
Authors: GUSTAV FüTTERER
Journal: JAMA (1904)

As the observations on epithelial metaplasia to be reported in this paper were made in a series of experiments on the stomach of rabbits, undertaken for the purpose of studying the relations between mechanical irritation and development of carcinoma, I think it necessary to state this fact, merely to show under what circumstances the findings were made. My views concerning the rôle which mechanical irritations play in the etiology of carcinoma, and how those views have been formed, have been fully explained in former writings, and I can, therefore, refer the reader to them, in order to prevent repetitions, which would make this article too extensive.<sup>1</sup> Some observations of importance have been made which I do not report, because they need corroboration, but they certainly encourage further efforts along the same lines.
Medical secretaries have a key role in helping patients navigate the NHS
Authors: H. Ward, S. Day
Journal: BMJ (2013)

We agree that much communication can be done directly by doctors, but Spence underestimates the role that medical secretaries play.1 Consultants’ secretaries are not merely typists and diary managers. They can play a key role in helping patients navigate the complex bureaucracy of the NHS.

Recent interviews that we conducted on patient experience of cancer …
Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor
Authors: Chiaki Takahashi, Bernardo Contreras, Tsuyoshi Iwanaga, Yujiro Takegami, Anke Bakker, Roderick T Bronson, Makoto Noda, Massimo Loda, Jennifer L Hunt, Mark E Ewen
Journal: Nature Genetics (2005)
Regulation of the Immune Response by Idiotypic-Antiidiotypic Interactions
Authors: Raif S. Geha
Journal: New England Journal of Medicine (1981)

THE antigen specificity of the antibody is determined by the variable (V) sequences of the hundred or so amino acid residues at the amino-terminal end of each of the heavy (H) and light (L) polypeptide chains of the antibody molecule (Fig. 1); the remaining constant amino acid sequences from the constant (C) domains determine the class of antibodies to which the molecule belongs.Two types of heterogeneity are present among antibody molecules. Heterogeneity I distinguishes about 20 classes of molecules in their C domains (isotypes) and distinguishes within each class a limited number of differences resulting from genetic polymorphism within . . .
Progress on health inequalities disappointing despite extra funding
Authors: H. Mooney
Journal: BMJ (2010)

Primary care trusts and local authorities are being swamped with too much policy and guidance aimed at finding ways to reduce health inequalities while the health gap between rich and poor continues to widen, the spending watchdog has said.

A report from the Audit Commission concludes that despite billions of pounds of investment health inequalities remain.

In 2009-10, the commission estimates that the NHS allocated £21bn (€23bn; $31bn) to primary care trusts to reflect differences in health inequalities. But despite this spend there has been a widening gap between the poor and the better off.

The report …
Prognostic Implications of p53 Nuclear Overexpression and High Proliferation Index of Ki-67 in Adult Soft-Tissue Sarcomas
Authors: Marija Drobnjak, Esther Latres, Daphna Pollack, Martin Karpeh, Maria Dudas, James M. Woodruff, Murray F. Brennan, Carlos Cordon-Cardo
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Prognostic Implications of p53 Nuclear Overexpression and High Proliferation Index of Ki-67 in Adult Soft-Tissue Sarcomas Get access Marija Drobnjak, Marija Drobnjak Search for other works by this author on: Oxford Academic PubMed Google Scholar Esther Latres, Esther Latres Search for other works by this author on: Oxford Academic PubMed Google Scholar Daphna Pollack, Daphna Pollack Search for other works by this author on: Oxford Academic PubMed Google Scholar Martin Karpeh, Martin Karpeh Search for other works by this author on: Oxford Academic PubMed Google Scholar Maria Dudas, Maria Dudas Search for other works by this author on: Oxford Academic PubMed Google Scholar James M. Woodruff, James M. Woodruff Search for other works by this author on: Oxford Academic PubMed Google Scholar Murray F. Brennan, Murray F. Brennan Search for other works by this author on: Oxford Academic PubMed Google Scholar Carlos Cordon-Cardo Carlos Cordon-Cardo Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 7, 6 April 1994, Pages 549–554, https://doi.org/10.1093/jnci/86.7.549 Published: 06 April 1994 Article history Received: 22 June 1993 Revision received: 14 December 1993 Accepted: 10 January 1994 Published: 06 April 1994
Administration of Wine and Grape Juice Inhibits In Vivo Platelet Activity and Thrombosis in Stenosed Canine Coronary Arteries
Authors: Heather S. Demrow, Peter R. Slane, John D. Folts
Journal: Circulation (1995)

Background Moderate daily consumption of alcoholic beverages is a negative risk factor for the development of atherosclerosis and coronary artery disease (CAD), especially in France and other Mediterranean areas where red wine is regularly consumed with meals. Platelets contribute to the development of atherosclerosis, CAD, and acute arterial thrombus formation. Methods and Results Anesthetized dogs were prepared with the Folts model of mechanically stenosed coronary arteries and intimal damage. Periodic acute platelet-mediated thrombus formation occurred, causing cyclic flow reductions (CFRs) in coronary blood flow. The CFRs were eliminated by the administration of 1.62±1.12 mL/kg red wine intravenously (IV) and 4.0 mL/kg intragastrically (IG). The CFRs were abolished by 2.04±1.42 mL/kg of grape juice IV and 10 mL/kg IG. White wine did not have significant results in eliminating the CFRs, either IV (2.0 mL/kg) or IG (4.0 mL/kg), decreasing the slopes of the CFRs only slightly. Conclusions Pure ethanol has been shown to inhibit platelet aggregation in vitro, ex vivo, and in vivo, although a blood alcohol content (BAC) of ≥0.2 g/dL is usually required. The BAC of dogs administered the red wine–saline solution intravenously was 0.028 g/dL, much less than is usually necessary for platelet inhibition with pure ethanol. Because red wine and grape juice, but not white wine, abolished the CFRs, this suggests there are compounds present in red wine and grape juice that are not present or are present in a lower concentration in white wine. Wine and grape juice contain a wide variety of naturally occurring compounds, including fungicides, tannins, anthocyanins, and phenolic flavonoids (including flavonols and flavones). These compounds have shown platelet inhibition in vitro by a variety of proposed mechanisms. Perhaps the biological activity of these compounds can explain the platelet-inhibitory properties of red wine and grape juice that are observed without high levels of ethanol.