tbuckley/cabot-search huggingface dataset:
Nature of Species Differences in the Medial Distribution of Aortic Vasa Vasorum in Mammals
Authors: HARVEY WOLINSKY, SEYMOUR GLAGOV
Journal: Circulation Research (1967)

Thoracic aortic segments of 12 mammalian species were fixed while distended at normal physiological pressures after the vasa vasorum were filled by a perfusion mixture containing gelatin and carbon. Mammals whose aortas had 29 or fewer medial lamellar units had no demonstrable intramural vascular channels; those whose aortas had more than 29 medial lamellar units, had medial vasa. Aortas with medial vasa vasorum always had a subintimal medial zone devoid of vasa vasorum. In growing animals the width of this avascular zone increased with age; in adults, the width increased slightly with increasing species body weight. However, the number of lamellar units in the avascular zone was independent of both age and species and equal to 29.0 ± 2.5. All of the species with intramural aortic vasa vasorum as adults had 29 or more aortic medial lamellar units at birth; none of the species which had 29 or fewer lamellar units at birth had more than 29 lamellar units at maturity. In aortas with medial vasa vasorum, widening of the avascular zone during growth appeared to be due only to the uniform thickening of each of the approximately 29 lamellar units already present at birth; the vascularized outer zone widened both by enlargement of its lamellar units and the addition of new lamellar units. Species differences in medial distribution of vasa vasorum are due primarily to differences in thickness of the vascularized outer zone.
Breast Cancer Risk by Breast Density, Menopause, and Postmenopausal Hormone Therapy Use
Authors: Karla Kerlikowske, Andrea J. Cook, Diana S.M. Buist, Steve R. Cummings, Celine Vachon, Pamela Vacek, Diana L. Miglioretti
Journal: Journal of Clinical Oncology (2010)

Purpose We determined whether the association between breast density and breast cancer risk and cancer severity differs according to menopausal status and postmenopausal hormone therapy (HT) use. Methods We collected data on 587,369 women who underwent 1,349,027 screening mammography examinations; 14,090 women were diagnosed with breast cancer. We calculated 5-year breast cancer risk from a survival model for subgroups of women classified by their Breast Imaging Reporting and Data System (BIRADS) breast density, age, menopausal status, and current HT use, assuming a body mass index of 25 kg/m 2 . Odds of advanced (ie, IIb, III, IV) versus early (ie, I, IIa) stage invasive cancer was calculated according to BIRADS density. Results Breast cancer risk was low among women with low density (BIRADS-1): women age 55 to 59 years, 5-year risk was 0.8% (95% CI, 0.6 to 0.9%) for non-HT users and 0.9% (95% CI, 0.7% to 1.1%) for estrogen and estrogen plus progestin users. Breast cancer risk was high among women with very high density (BIRADS-4), particularly estrogen plus progestin users: women age 55 to 59 years, 5-year risk was 2.4% (95% CI, 2.0% to 2.8%) for non-HT users, 3.0% (95% CI, 2.6% to 3.5%) for estrogen users, and 4.2% (95% CI, 3.7% to 4.6%) for estrogen plus progestin users. Advanced-stage breast cancer risk was increased 1.7-fold for postmenopausal HT users who had very high density (BIRADS-4) compared to those with average density (BIRADS-2). Conclusion Postmenopausal women with high breast density are at increased risk of breast cancer and should be aware of the added risk of taking HT, especially estrogen plus progestin.
ON CERTAIN SPONTANEOUS CHICKEN TUMORS AS MANIFESTATIONS OF A SINGLE DISEASE
Authors: Peyton Rous
Journal: The Journal of Experimental Medicine (1914)

Two spontaneous chicken tumors, unlike in several important respects, have given rise on transplantation to neoplasms of identical character. The spontaneous growth, No. 18, situated in the gizzard, was a spindle-celled sarcoma rifted with blood sinuses into which it extended, with result in what may be described as an intracanalicular pattern. The metastases, which were in the voluntary muscles, showed the same peculiar structure. Tumor 38, occurring in the subcutaneous tissue of the groin, was a solid, spindle-celled sarcoma of rather close texture, with few blood vessels. Here and there were small areas of softening, and at its center was a large degeneration cyst with ragged walls, containing a clear fluid. There were no metastases. The transplantation tumors from both growths have been characterized by slow growth, tendency to metastasize to the skeletal muscles without involvement of the lungs, and a structure which at one time is that of a very regular spindle-celled sarcoma containing many bands and ribbons of collagen, and at another that of a sarcoma rifted with blood sinuses like the spontaneous tumor No. 18. At present the two strains are practically indistinguishable in appearance and general behavior. Both are caused by filterable agents. The agent causing No. 38, unlike that causing No. 18, retains its activity in tumor tissue which has been dried or glycerinated; and in a Berkefeld filtrate it is much the more active in causing tumors. These differences can hardly be thought of as constituting a fundamental distinction between agents which, to judge from their effects, are almost undoubtedly different strains of a single disease cause. That chicken tumors of markedly different type have different filterable agents as their cause has been proved by experiments already reported. The present findings make it probable that, within certain limits, tumors of rather various character may be dependent upon a single agent. This assumption greatly simplifies the etiological problem. But the truth of the assumption for other instances than those described in the present article can only be determined by the study and comparison in many hosts of the disease-complexes of which each spontaneous chicken tumor is to be considered as an individual expression.
The Cost-effectiveness of Counseling Smokers to Quit
Authors: Steven R. Cummings
Journal: JAMA (1989)

Cigarette smoking is the most important preventable cause of death in the United States. Surveys of patients, however, suggest that many physicians do not routinely counsel smokers to quit. Because physicians may not consider counseling against smoking to be as worthwhile as other medical practices, we examined its cost-effectiveness. We based our estimates of the effectiveness of physician counseling on published reports of randomized trials and our estimates of its cost on average charges for physician office visits. Our results indicate that the cost-effectiveness of brief advice during routine office visits ranges from $705 to $988 per year of life saved for men and from $1204 to $2058 for women. Follow-up visits about smoking appear to be similarly cost-effective. Physician counseling against smoking, therefore, is at least as cost-effective as several other preventive medical practices and should be a routine part of health care for patients who smoke. (<i>JAMA</i>1989;261:75-79)
Referral criteria in early rheumatoid arthritis
Authors: V. Quincey, R Hull, D Sinclair
Journal: Journal of the Royal Society of Medicine (2004)

Dr Suresh (September 2004 JRSM1) highlights the importance of early referral in a patient with suspected rheumatoid arthritis or RA-like polyarthritis. As he indicates, the diagnosis is a clinical one and absence of rheumatoid factor (RF) is not informative. Unfortunately, there is reason to think some general practitioners delay referral when the serology is negative. Sinclair and Hull,2 looked at the reasons general practitioners request RF assays and the effect of the result on their subsequent action. The requests were generally backed by appropriate clinical signs of RA; however, 32% of responders believed that a negative RF excluded RA, even in a patient who fulfilled the American Rheumatism Association4 classification criteria. Referrals were made to a consultant rheumatologist in 52% of patients with a positive RF, but 66% of patients with a negative RF would not be referred. In only 1.2–2.5% of instances were patients referred for specialist review on clinical grounds alone. Seronegative RA should account for about 25% of total cases. With 60% of cases seronegative at presentation,5 the above data suggest that a sizeable number of RA patients are being missed. Should RF be removed from the decision-making process? If general practitioners relied wholly on clinical criteria and the RF test was restricted to rheumatologists only, we could expect a large increase in consultant referrals.
AXON RETRACTION AND DEGENERATION IN DEVELOPMENT AND DISEASE
Authors: Liqun Luo, Dennis D.M. O'Leary
Journal: Annual Review of Neuroscience (2005)

The selective elimination of axons, dendrites, axon and dendrite branches, and synapses, without loss of the parent neurons, occurs during normal development of the nervous system as well as in response to injury or disease in the adult. The widespread developmental phenomena of exuberant axonal projections and synaptic connections require both small-scale and large-scale axon pruning to generate precise adult connectivity, and they provide a mechanism for neural plasticity in the developing and adult nervous system, as well as a mechanism to evolve differences between species in a projection system. Such pruning is also required to remove axonal connections damaged in the adult, to stabilize the affected neural circuits, and to initiate their repair. Pruning occurs through either retraction or degeneration. Here we review examples of these phenomena and consider potential cellular and molecular mechanisms that underlie axon retraction and degeneration and how they might relate to each other in development and disease.
Functional and Biochemical Analysis of Endothelial (Dys)function and NO/cGMP Signaling in Human Blood Vessels With and Without Nitroglycerin Pretreatment
Authors: Eberhard Schulz, Nikolaus Tsilimingas, Ruth Rinze, Beate Reiter, Maria Wendt, Mathias Oelze, Silke Woelken-Weckmüller, Ulrich Walter, Hermann Reichenspurner, Thomas Meinertz, Thomas Münzel
Journal: Circulation (2002)

In experimental animal models, long-term in vivo treatment with nitroglycerin (NTG) induces both endothelial dysfunction and tolerance to nitrates. However, it is still controversial whether nitrate tolerance in humans is associated with both endothelial dysfunction and impaired vascular response to nitrovasodilator-derived NO.Patients undergoing elective bypass surgery were randomized to receive 48 hours of continuous NTG infusion (NTG group) or no nitrate therapy (control group). Segments of surgically removed arteria mammaria, vena saphena, and arteria radialis not required for the bypass procedure were used to examine (1) the vascular responsiveness to NTG and the endothelium-dependent vasodilator acetylcholine; (2) the expression of the NO target, the soluble guanylyl cyclase; (3) the expression of the soluble guanylyl cyclase/cGMP effector target, the cGMP-dependent protein kinase (cGK); and (4) the cGK activity as assessed by the phosphorylation state of its vascular substrate, the vasodilator-stimulated phosphoprotein at serine(239) (P-VASP). NTG treatment caused a marked degree of nitrate tolerance in all 3 vessel types studied and a significant cross-tolerance to the endothelium-dependent vasodilator acetylcholine in A. mammaria and A. radialis. Although soluble guanylyl cyclase, cGK-I, and VASP expression levels were not modified by NTG treatment, a marked decrease of P-VASP, a surrogate parameter for in-vivo cGK-I activity, was observed.We conclude that long-term NTG treatment induces endothelial dysfunction and impaired vascular NO/cGMP signaling in humans, which can be monitored by measuring P-VASP levels.
MOLECULAR MECHANISM OF 7TM RECEPTOR ACTIVATION—A GLOBAL TOGGLE SWITCH MODEL
Authors: Thue W. Schwartz, Thomas M. Frimurer, Birgitte Holst, Mette M. Rosenkilde, Christian E. Elling
Journal: The Annual Review of Pharmacology and Toxicology (2006)

The multitude of chemically highly different agonists for 7TM receptors apparently do not share a common binding mode or active site but nevertheless act through induction of a common molecular activation mechanism. A global toggle switch model is proposed for this activation mechanism to reconcile the accumulated biophysical data supporting an outward rigid-body movement of the intracellular segments, as well as the recent data derived from activating metal ion sites and tethered ligands, which suggests an opposite, inward movement of the extracellular segments of the transmembrane helices. According to this model, a vertical see-saw movement of TM-VI-and to some degree TM-VII-around a pivot corresponding to the highly conserved prolines will occur during receptor activation, which may involve the outer segment of TM-V in an as yet unclear fashion. Small-molecule agonists can stabilize such a proposed active conformation, where the extracellular segments of TM-VI and -VII are bent inward toward TM-III, by acting as molecular glue deep in the main ligand-binding pocket between the helices, whereas larger agonists, peptides, and proteins can stabilize a similar active conformation by acting as Velcro at the extracellular ends of the helices and the connecting loops.
Effects of PHEX Antisense in Human Osteoblast Cells
Authors: Nengjen Remi Shih, Oak D. Jo, Norimoto Yanagawa
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. X-linked hypophosphatemia (XLH) is an X-linked dominant disorder that is characterized by rachitic bone disease and hypophosphatemia due to renal phosphate transport defect. The candidate gene for XLH, PHEX, has recently been identified and found to share high homology with endopeptidases. PHEX is expressed in various tissues, including bones, and the available evidence today indicates that bones can release abnormal humoral factors that affect bone mineralization and proximal tubule phosphate transport in XLH. It was, therefore, hypothesized that the inactivating mutations of PHEX in bone may lead to the release of humoral factors and contribute to the phenotypic expression of the disease. To test this possibility, clones of MG-63 cells, a human osteoblast cell line, were produced and stably transfected with PHEX-antisense vectors, resulting in a decrease in PHEX expression at mRNA and protein levels. It was found that these antisense-transfected cells had impaired mineralization, with a decrease in 45Ca incorporation and calcification nodule formation. It was also found that the conditioned culture media collected from these antisense-transfected cells exhibited inhibitory activities on 45Ca incorporation by the nontransfected MG-63 cells and 32P uptake by the opossum kidney proximal tubular cells. The results of the study, therefore, provide strong evidence that supports the link between PHEX mutations and the pathogenesis of XLH.
Vaginal Colonization with<i>Staphylococcus aureus</i>in Healthy Women
Authors: MARY E. GUINAN
Journal: Annals of Internal Medicine (1982)

Four studies assessed the frequency of vaginal Staphylococcus aureus colonization in healthy women and associated risk factors. An association was found between S. aureus vaginal colonization and colonization at the labia minora and the anterior nares. Significant risk factors associated with an increased risk of vaginal S. aureus in at least one study were a history of genital herpes simplex infection, insertion of tampons without an applicator, and the use of Rely (Procter & Gamble) tampons. The use of systemic antibiotics within 2 weeks of the vaginal culture decreased the risk of recovery of S. aureus. The overall frequency of vaginal S. aureus in the 808 women in the four studies was 9.2%.
Large CSF Volume Not Attributable to Ventricular Volume in Schizotypal Personality Disorder
Authors: Chandlee C. Dickey, Martha E. Shenton, Yoshio Hirayasu, Iris Fischer, Martina M. Voglmaier, Margaret A. Niznikiewicz, Larry J. Seidman, Stephanie Fraone, Robert W. McCarley
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The purpose of this study was to determine whether schizotypal personality disorder, which has the same genetic diathesis as schizophrenia, manifests abnormalities in whole-brain and CSF volumes. METHOD: Sixteen right-handed and neuroleptic-naive men with schizotypal personality disorder were recruited from the community and were age-matched to 14 healthy comparison subjects. Magnetic resonance images were obtained from the subjects and automatically parcellated into CSF, gray matter, and white matter. Subsequent manual editing separated cortical from noncortical gray matter. Lateral ventricles and temporal horns were also delineated. RESULTS: The men with schizotypal personality disorder had larger CSF volumes than the comparison subjects; the difference was not attributable to larger lateral ventricles. The cortical gray matter was somewhat smaller in the men with schizotypal personality disorder, but the difference was not statistically significant. CONCLUSIONS: Consistent with many studies of schizophrenia, this examination of schizotypal personality disorder indicated abnormalities in brain CSF volumes.
The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults
Authors: Rosanna Coppo, Stéphan Troyanov, Roberta Camilla, Ronald J. Hogg, Daniel C. Cattran, H. Terence Cook, John Feehally, Ian S.D. Roberts, Alessandro Amore, Charles E. Alpers, Jonathan Barratt, Francois Berthoux, Stephen Bonsib, Jan A. Bruijn, Vivette D'Agati, Giuseppe D'Amico, Steven N. Emancipator, Francesco Emma, Franco Ferrario, Fernando C. Fervenza, Sandrine Florquin, Agnes B. Fogo, Colin C. Geddes, Hermann J. Groene, Mark Haas, Andrew M. Herzenberg, Prue A. Hill, Stephen I. Hsu, J. Charles Jennette, Kensuke Joh, Bruce A. Julian, Tetsuya Kawamura, Fernand M. Lai, Lei S. Li, Philip K. Li, Zhi H. Liu, Sergio Mezzano, F. Paolo Schena, Yasuhiko Tomino, Patrick D. Walker, Haiyan Wang, Jan J. Weening, Norishige Yoshikawa, Hong Zhang
Journal: Kidney International (2010)
Induction of necrosis but not apoptosis after anoxia and reoxygenation in isolated adult cardiomyocytes of rat
Authors: G Taimor, H Lorenz, B Hofstaetter, K.-D Schlüter, H.M Piper
Journal: Cardiovascular Research (1999)

Objectives: Apoptosis is one feature of myocardial damage after ischemia–reperfusion, but the causes for its induction are unclear. The present study was undertaken to investigate whether apoptosis in cardiomyocytes is directly initiated by their sub-lethal injury that results from ischemia–reperfusion. Methods: Ischemia was simulated on isolated ventricular cardiomyocytes of adult rats by anoxia in a glucose free medium, pH 6.4. Induction of apoptosis was detected by (1) DNA laddering of genomic DNA, (2) TUNEL positive cells (terminal deoxynucleotidyl transferase-mediated-UTP nick end labelling) and (3) annexinV–fluorescein isothiocyanate (annexinV–FITC) binding to cells under exclusion of propidium iodide. Necrotic cells were identified by (1) staining with both annexinV–FITC and propidium iodide, (2) unspecific DNA degradation and (3) enzyme release. Results: Simulated ischemia caused a >75% loss of high-energy phosphates within 2 h, which was reversible upon reoxygenation at pH 7.4. Even after 18 h of simulated ischemia, creatine phosphate contents recovered to 55.2±7.3% of control within 1 h. Apoptosis could be induced by UV irradiation (80 J/m2), H2O2 and the NO-donor N2-acetyl-S-nitroso-d,l-penicillinaminamide. In contrast to this, simulated ischemia and reoxygenation could not induce apoptosis in the cells, but with prolonged ischemia more cells became necrotic. After 18 hours of simulated ischemia and 4 h of reoxygenation 41.2±10.2% myocytes were necrotic (vs. 6.3±4.4% of control) and only 1.7±0.5% (vs. 8.7±4.6% of control) were apoptotic. The percentage of necrotic cells correlated with an increase in lactate dehydrogenase release from 9.9±0.6% (of total activity) of normoxic controls to 37.9±5.1% after 18 h of simulated ischemia and 12 h of reoxygenation. Conclusions: Simulated ischemia-reoxygenation causes necrosis of isolated cardiomyocytes but is not sufficient for induction of apoptosis.
Investigating the Role of Nucleotide-Binding Oligomerization Domain–Like Receptors in Bacterial Lung Infection
Authors: Mary Leissinger, Ritwij Kulkarni, Rachel L. Zemans, Gregory P. Downey, Samithamby Jeyaseelan
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Lower respiratory tract infections (LRTIs) are a persistent and pervasive public health problem worldwide. Pneumonia and other LRTIs will be among the leading causes of death in adults, and pneumonia is the single largest cause of death in children. LRTIs are also an important cause of acute lung injury and acute exacerbations of chronic obstructive pulmonary disease. Because innate immunity is the first line of defense against pathogens, understanding the role of innate immunity in the pulmonary system is of paramount importance. Pattern recognition molecules (PRMs) that recognize microbial-associated molecular patterns are an integral component of the innate immune system and are located in both cell membranes and cytosol. Toll-like receptors and nucleotide-binding oligomerization domain-like receptors (NLRs) are the major sensors at the forefront of pathogen recognition. Although Toll-like receptors have been extensively studied in host immunity, NLRs have diverse and important roles in immune and inflammatory responses, ranging from antimicrobial properties to adaptive immune responses. The lung contains NLR-expressing immune cells such as leukocytes and nonimmune cells such as epithelial cells that are in constant and close contact with invading microbes. This pulmonary perspective addresses our current understanding of the structure and function of NLR family members, highlighting advances and gaps in knowledge, with a specific focus on immune responses in the respiratory tract during bacterial infection. Further advances in exploring cellular and molecular responses to bacterial pathogens are critical to develop improved strategies to treat and prevent devastating infectious diseases of the lung.
Bronchial Nitric Oxide Flux May Be Better Associated with Inducible Nitric Oxide Synthase Promoter Methylation
Authors: Julie Kuriakose, Maria José Rosa, Matthew Perzanowski, Rachel Miller
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

therapeutic target" for pharmacologic interventions in IPF.Thus, at our current state of knowledge, we believe that it is a reasonable approach to try to identify mediators and pathways that are crucially involved in this fatal disease and that might serve as targets for therapeutic interventions.We also believe that, in the end, effective treatment of IPF is likely to require a combination of therapies targeting multiple mediators/signaling pathways.
Malignant hypertension and hypertensive emergencies.
Authors: C Kitiyakara, N J Guzman
Journal: Journal of the American Society of Nephrology (1998)

Hypertensive emergencies and urgencies are important causes of morbidity and mortality. Malignant hypertension is a hypertensive urgency characterized by grade III/IV retinopathy and widespread endothelial damage. Control of BP is essential in the treatment of these disorders. The effects of hypertension on target organ function need to be balanced against the risks of excessive BP lowering. In hypertensive emergencies, BP should be lowered within minutes with parenteral agents to prevent critical end-organ damage. In hypertensive urgencies, BP can be lowered more slowly over several hours, often with oral agents, to avoid a detrimental fall in BP. The absolute indications for treatment and the optimal therapy depend on the underlying condition.