tbuckley/cabot-search huggingface dataset:
Prognostic Implications of Abnormalities in Renal Function in Patients With Acute Coronary Syndromes
Authors: Jassim Al Suwaidi, Donal N. Reddan, Kathryn Williams, Karen S. Pieper, Robert A. Harrington, Robert M. Califf, Christopher B. Granger, E. Magnus Ohman, David R. Holmes
Journal: Circulation (2002)

Background— Outcomes in patients with mild to moderate renal function (RF) abnormalities presenting with acute coronary syndromes (ACS) are not well defined. Methods and Results— A convenience sample of 4 ACS trial databases including all enrolled patients was assessed to determine 30- and 180-day outcomes. The 4 trials were Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb, GUSTO-III, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON-A). Patients were stratified into ST-segment elevation (STE) and non–ST-segment elevation (NSE) groups and by the presence or absence of abnormal RF (creatinine clearance &lt;70 mL/min). In the STE group, 7670 of 18 621 patients (41%) had abnormal RF. In the NSE group, 8152 of 19 304 (42%) had abnormal RF. Patients with abnormal RF were older, more often female, and more likely to have adverse baseline characteristics. They had higher mortality and higher mortality/nonfatal myocardial infarction (MI) at both 30 and 180 days, regardless of ST-segment status. Creatinine clearance was independently associated with risk of mortality (hazard ratio 0.79 in the STE group and 0.81 in the NSE group) and with risk of mortality/MI (hazard ratio 0.93) in the NSE group at 180 days. Conclusions— Patients presenting with ACS frequently have abnormal RF. Abnormal RF is a marker of adverse baseline clinical characteristics and is independently associated with increased risk of death and death/MI.
Kidney Disease as a Risk Factor for Development of Cardiovascular Disease
Authors: Mark J. Sarnak, Andrew S. Levey, Anton C. Schoolwerth, Josef Coresh, Bruce Culleton, L. Lee Hamm, Peter A. McCullough, Bertram L. Kasiske, Ellie Kelepouris, Michael J. Klag, Patrick Parfrey, Marc Pfeffer, Leopoldo Raij, David J. Spinosa, Peter W. Wilson
Journal: Circulation (2003)

HomeCirculationVol. 108, No. 17Kidney Disease as a Risk Factor for Development of Cardiovascular Disease
JAPANESE PSYCHIATRY AND PSYCHOTHERAPY
Authors: AVROHM JACOBSON, ALBERT N. BERENBERG
Journal: American Journal of Psychiatry (1952)

An attempt is made to give some of the philosophy and methods that underlie present-day Japanese psychiatry. A brief discussion of psychosis is given. The classification of "shinkeishitsu" with its subgroupings of neurasthenic states, obsessive-phobic states, and paroxysmal neurosis is outlined and discussed. Monita's 4-phase therapy for treating "shinkeishitsu" is presented together with statistics compiled by the Kyushu University Medical School department of neuropsychiatry. Cultural factors such as Buddhistic influences, national traditions, and cultural patterns are elaborated where they relate to the classification and treatment of mental diseases in Japan. Symptoms characteristic of "shinkeishitsu" are listed with their frequency of occurrence as they were observed at the Kyushu Medical School Clinic. An attempt is made to explain these symptoms on the basis of cultural and historical factors. Some of the limitations of the Japanese approach to psychotherapy as exemplified by Monita's treatment of "shinkeishitsu" are discussed.
Applications of Monoclonal Antibodies to Neuroscience Research
Authors: Karen L. Valentino, Janet Winter, Louis F. Reichardt
Journal: Annual Review of Neuroscience (1985)

The preceding discussion documents the diverse ways in which monoclonal antibodies have contributed to neuroscience research. They provide highly specific reagents to membrane-associated proteins, such as pumps, channels, receptors, and cell-adhesion molecules, that are useful for purifying these proteins, studying their structures at high resolution, and mapping their distributions. In many cases, the specific reagents were obtained using only partially purified antigens. Monoclonal antibodies to cytoskeletal proteins, organelles, and protein kinases have revealed that specific molecules are concentrated in anatomically distinct regions of the cell. A protein kinase has been shown to be a major postsynaptic constituent in many synapses. Individual proteins, such as actin, tubulin, and calmodulin appear to have different antigenic epitopes shielded in different parts of the cell. Monoclonal antibodies have provided a diversity of cell-type-specific reagents in both vertebrate and invertebrate nervous systems. They seem likely to be useful in identifying functionally related subpopulations of neurons and describing neural cell lineages. They will also serve to identify molecules that are important in regulating cell migration in the cerebellum, in marking cell position in the retina, and directing axon growth. This review also documents many purposes for which monoclonal antibodies are poorly suited or must be used with caution: A monoclonal antibody to a protein does not always reveal every place where that molecule is located. Pre- or post-translational microheterogeneity can expose different epitopes on the protein, such as may occur on the Na+-channel. Other proteins within the cell may shield antigenic sites on proteins such as calmodulin. Monoclonal antibodies can bind to epitopes on unrelated molecules (Nigg et al 1982, Lane & Koprowski 1982). This is revealed in some cases as multiple bands on immunoblots. Some cross-reactivity, however, may have a functional basis. For example, structural homology is clearly the basis for the antigenic epitopes that are shared among the five classes of intermediate filaments (Pruss et al 1981). The epitope that appears to be shared between the muscarinic and alpha 1-adrenergic receptors may be conserved because the two receptors modulate common effectors. The cross-reactivity between these receptors was only recognized because very specific and sensitive assays exist for each. It is quite possible that these same antibodies also bind sites on many other types of receptors. Mapping the distribution of this epitope may therefore have little relationship to the actual distribution of the muscarinic receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
Do movement planning and control represent independent modules?
Authors: Valérie Gaveau, Michel Desmurget
Journal: Behavioral and Brain Sciences (2004)

We address three issues that might be important in evaluating the validity of the planning–control model: (1) It could be artificial to distinguish between control and planning when control involves the re-planning of a new corrective submovement that overlaps with the initial response; (2) experiments involving illusions are not totally compelling; (3) selectively implicating the superior parietal lobe in movement control and the basal ganglia in movement planning, appears questionable.
Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo
Authors: Andre Broermann, Mark Winderlich, Helena Block, Maike Frye, Jan Rossaint, Alexander Zarbock, Giuseppe Cagna, Ruth Linnepe, Dörte Schulte, Astrid Fee Nottebaum, Dietmar Vestweber
Journal: The Journal of Experimental Medicine (2011)

We have recently shown that vascular endothelial protein tyrosine phosphatase (VE-PTP), an endothelial membrane protein, associates with VE-cadherin and is required for optimal VE-cadherin function and endothelial cell contact integrity. The dissociation of VE-PTP from VE-cadherin is triggered by vascular endothelial growth factor (VEGF) and by the binding of leukocytes to endothelial cells in vitro, suggesting that this dissociation is a prerequisite for the destabilization of endothelial cell contacts. Here, we show that VE-cadherin/VE-PTP dissociation also occurs in vivo in response to LPS stimulation of the lung or systemic VEGF stimulation. To show that this dissociation is indeed necessary in vivo for leukocyte extravasation and VEGF-induced vascular permeability, we generated knock-in mice expressing the fusion proteins VE-cadherin-FK 506 binding protein and VE-PTP-FRB* under the control of the endogenous VE-cadherin promoter, thus replacing endogenous VE-cadherin. The additional domains in both fusion proteins allow the heterodimeric complex to be stabilized by a chemical compound (rapalog). We found that intravenous application of the rapalog strongly inhibited VEGF-induced (skin) and LPS-induced (lung) vascular permeability and inhibited neutrophil extravasation in the IL-1β inflamed cremaster and the LPS-inflamed lung. We conclude that the dissociation of VE-PTP from VE-cadherin is indeed required in vivo for the opening of endothelial cell contacts during induction of vascular permeability and leukocyte extravasation.
Treatment and Outcome of 83 Children With Intraspinal Neuroblastoma: The Pediatric Oncology Group Experience
Authors: Howard M. Katzenstein, Paul M. Kent, Wendy B. London, Susan L. Cohn
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To investigate whether the rate of neurologic recovery or the incidence of long-term sequelae differed for children with neuroblastoma (NB) initially treated with chemotherapy versus surgical decompression with laminectomy, we reviewed the Pediatric Oncology Group (POG) experience. PATIENTS AND METHODS: A retrospective review of children diagnosed with intraspinal NB registered on POG NB Biology Protocol 9047 was performed. Survival, neurologic outcome, and orthopedic sequelae were evaluated according to age of the patient at diagnosis, stage of disease, duration and severity of neurologic symptoms, and therapeutic intervention. RESULTS: Between May 1990 and January 1998, 83 children with intraspinal NB were entered onto the study. Five-year survival for this cohort of patients was 71% ± 9%. Forty-three (52%) of the patients had neurologic symptoms at diagnosis. After treatment, six of 15 severely affected patients, who presented with paralysis, completely recovered neurologic function. Two of five patients with moderate deficits, consisting of paresis and bowel/bladder dysfunction, completely recovered neurologic function. Seventeen of 22 assessable children, who had mild symptoms comprised of paresis alone, fully recovered. Seven of 24 assessable patients who had undergone laminectomy developed scoliosis, whereas spinal deformities were only detected in one of 49 assessable patients managed without laminectomy (P = .001). CONCLUSION: The frequency of complete neurologic recovery in children with intraspinal NB inversely correlated with the severity of the presenting neurologic deficits. The rate of neurologic recovery was similar for patients treated with chemotherapy compared to those managed with laminectomy. Fewer orthopedic sequelae were observed in the children managed with chemotherapy than were seen in children managed with laminectomy.
Human Diaphragm Remodeling Associated with Chronic Obstructive Pulmonary Disease
Authors: Sanford Levine, Taitan Nguyen, Larry R. Kaiser, Neal A. Rubinstein, Greg Maislin, Christopher Gregory, Lawrence C. Rome, Gary A. Dudley, Gary C. Sieck, Joseph B. Shrager
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Diaphragm remodeling associated with chronic obstructive pulmonary disease (COPD) consists of a fast-to-slow fiber type transformation as well as adaptations within each fiber type. To try to explain disparate findings in the literature regarding the relationship between fiber type proportions and FEV1, we obtained costal diaphragm biopsies on 40 subjects whose FEV1 ranged from 118 to 16% of the predicted normal value. First, we noted that our exponential regression model indicated that changes in FEV1 can account for 72% of the variation in the proportion of Type I fibers. Second, to assess the impact of COPD on diaphragm force generation, we measured maximal specific force generated by single permeabilized fibers prepared from the diaphragms of two patients with normal pulmonary function tests and two patients with severe COPD. We noted that fibers prepared from the diaphragms of severe COPD patients generated a lower specific force than control fibers (p < 0.001) and Type I fibers generated a lower specific force than Type II fibers (p < 0.001). Our finding of an exponential relationship between the proportion of Type I fibers and FEV1 accounts for discrepancies in the literature. Moreover, our single-fiber results suggest that COPD-associated diaphragm remodeling decreases diaphragmatic force generation by adaptations within each fiber type as well as by fiber type transformations.
HYALURONATE IN NORMAL HUMAN SYNOVIAL FLUID1
Authors: David Hamerman, Hilda Schuster
Journal: Journal of Clinical Investigation (1958)

Studies on hyaluronate in normal human syno- vial fluid have been hindered by the high viscosity and small volume of fluid available.Reports on hyaluronate levels in normal synovial fluid, in which a number of different methods have been used, have shown discordant results (1-4).Several methods were used in the present study to determine the hyaluronate content of normal synovial fluid.Weighing rather than pipetting the small samples of viscous fluid made it possible to measure hyaluronate in 0.25 Gm. of synovial fluid.Hyaluronate was precipitated in mucin clots formed by adding acid or a polyvalent cation to synovial fluid, and was measured indirectly by determining hexosamine in these clots.Since a part of the hexosamine of synovial fluid is not a component of hyaluronate, an important aspect of this work was the demonstration that no non- hyaluronate hexosamine was precipitated in mucin clots, and that no hyaluronate hexosamine re- mained in the supernatant after a mucin clot was formed.Hyaluronate content of synovial fluid was also measured by determining the fall in hexosamine after hyaluronidase digestion and di- alysis of whole synovial fluid.Figures for hyaluronate in synovial fluid as determined by mucin clot technique, and by hyaluronidase digestion and dialysis of synovial fluid agreed, lending confi- dence in the validity of these methods. MATERIALS AND METHODSDeceased subjects were selected who died suddenly after traumatic injury or a vascular accident and who showed no obvious joint disease or systemic illness that might contribute to pathological joint effusions.Synovial fluid was obtained with sterile precautions from both knee joints within six hours after death.Fluids were frozen at -200 C. unless studied within 24 hours, in which case they were stored at 50 C.
Down-regulation of Insulin Receptor by Antibodies against the Type I Insulin-Like Growth Factor Receptor: Implications for Anti–Insulin-Like Growth Factor Therapy in Breast Cancer
Authors: Deepali Sachdev, Rajeeva Singh, Yoko Fujita-Yamaguchi, Douglas Yee
Journal: Cancer Research (2006)

Abstract Insulin-like growth factor-I (IGF-I), IGF-II, and insulin have all been implicated in regulating several aspects of the malignant phenotype via the type I IGF receptor (IGF1R) and insulin receptor (IR). We have previously shown that a chimeric single-chain antibody against IGF1R (scFv-Fc) and a murine antibody EM164 down-regulate IGF1R, making breast cancer cells unresponsive to IGF-I. To determine if IR signaling is affected, we examined regulation of IR in MCF-7 cells after exposure to these antibodies. Surprisingly, both scFv-Fc and EM164 resulted in decreased levels of IR in vitro and in vivo despite their lack of reactivity against IR. Twenty-four-hour pretreatment with EM164 also inhibited insulin-mediated phosphorylation of IR and insulin-stimulated proliferation of MCF-7 cells. Neither scFv-Fc nor EM164 caused down-regulation of IR in cells that express very low levels of IGF1R or no IGF1R. Expression of IGF1R was required for IR down-regulation, which was specific as neither antibody caused down-regulation of β1 integrin or epidermal growth factor receptor. Reagents that disrupt lipid rafts inhibited IR down-regulation by the antibodies, suggesting that IR in close physical proximity to IGF1R in lipid rafts was being endocytosed. Our data show that down-regulation of IR by monoclonal antibodies against IGF1R requires the coexpression of IGF1R and may be due to endocytosis of hybrid IR/IGF1R or holo-IR. Thus, antibodies against IGF1R provide inhibition of both IGF and insulin signaling in cancer cells. (Cancer Res 2006; 66(4): 2391-402)
Azithromycin therapy for neutrophilic airways disease: myth or magic?
Authors: S. F Idris, E. R Chilvers, C. Haworth, D. McKeon, A. M Condliffe
Journal: Thorax (2009)

The anti-inflammatory potential of macrolides was first appreciated with the successful use of erythromycin in the treatment of diffuse panbronchiolitis, a disease principally affecting the Japanese, and characterised by a persistent neutrophilic inflammatory infiltrate of the bronchi. While there are only limited data on the efficacy of other macrolides in treating this condition,1 the observation has generated considerable interest in examining the role of macrolides in other respiratory diseases where chronic airways inflammation is a prominent feature.

Azithromycin (AZM) is a 15-membered macrolactam ring macrolide which, in randomised controlled studies, has demonstrated a beneficial role in the treatment of cystic fibrosis (CF)2–5 despite its lack of direct bactericidal or bacteriostatic activity against Pseudomonas aeruginosa . More recent (albeit smaller) studies have suggested a role for AZM in the treatment of bronchiolitis obliterans syndrome (BOS)6 and asthma,7 with a common finding in both being its ability to reduce airway neutrophilia. Such observations have focused attention on understanding how AZM and other macrolides may modulate host-pathogen interactions in chronic lung infection and their role as an immunomodulatory agent in both respiratory and non-respiratory settings. Clinical studies have usually been designed to study an individual macrolide agent, but it is likely that the findings in such trials represent a “class effect”. Although some in vitro experiments have suggested subtle differences between individual class members, the in vivo significance of these observations is uncertain.

The direct antimicrobial activity of macrolides against Gram-positive bacteria results from inhibition of bacterial protein synthesis. Although AZM has little direct activity against Gram-negative organisms, it has been shown to modulate bacterial virulence factors and thus affect the outcome of chronic infections with organisms such as P aeruginosa . Quorum sensing is a sophisticated mechanism whereby pathogen-derived molecules act as auto-inducers and trigger a …
Methotrexate reduces immunogenicity in adalimumab treated rheumatoid arthritis patients in a dose dependent manner
Authors: Charlotte L Krieckaert, Michael T Nurmohamed, Gerrit Jan Wolbink
Journal: Annals of the Rheumatic Diseases (2012)

Immunogenicity of adalimumab could impair important treatment outcome parameters in patients with rheumatoid arthritis (RA). Patients who developed antiadalimumab antibodies (AAA) during a 3 year time period achieved less often minimal disease activity or remission and treatment failure occurred more often compared with patients without AAA.1 There were remarkable baseline differences: patients developing AAA had more long-standing, severe disease and less often used concomitant medication including lower doses of methotrexate (MTX), compared with patients not developing AAA. In literature, a favourable effect of concomitant MTX use on the immunogenicity of adalimumab for several inflammatory conditions is suggested.2

To investigate which MTX dose is sufficient to reduce immunogenicity, patients of …
Thomas's Operation for Removal of Benign Tumour of the Female Breast
Authors: A. Jamieson
Journal: BMJ (1888)

nine days he left hospital.On October 3rd, 1887, he started work, and whilst bending down to lift a sack, he was struck by a lightning shock of pain, which, starting at the supra-orbital notch, passed along the right side of the head as far as the occiput, and this acute pain occurred almost every time he bent his head down, and often on moving it from side to side.He therefore did his work holding the head in the erect posture, but in spite of this the pain now and again attacked him, and the eye becoming greatly irritable, he was again compelled to seek hospital treat- ment.This time a large iridectomy was performed upwards (October 15th, 1887), but the redness and irritability not subsiding, and the pain continuing, the removal of the eye was determined on.In this decision the patient acquiesced, but his employer ob- jecting, hle now came under my notice, November 8th, 1887.The right eye was very red, irritable, and watering much on exposure to light; V C + 12 D 20%: C + 14 D a few words of Ja 4. Just below the centreof the cornea there was a small cicatrix, and it was easy to see that an adhesion to the iris hlad existed here.A large upward iridectomy pupillary space was occupied by capsular remains.The iris was attachled firmly to these remains below and on the outer side, but it was free orL the innLer side.By means olf careful oblique Line of Incision Glass, actual Size.Glass in Situ.illumination, and whlen the ey'e was turned in celrtain directions, there could be seen lying in tlhe anterior chamber, in the sinus be- tween the cornea and iris, and not imbedded in the latter, a piece of glass, wvhich appeared to be quite a quarter of an inch long, and was of considerable breadth.The position of the glass was not
Diabetes mellitus, plasma glucose and lung function in a cross-sectional population study
Authors: P Lange, S Groth, J Kastrup, J Mortensen, M Appleyard, J Nyboe, G Jensen, P Schnohr
Journal: European Respiratory Journal (1989)

To assess possible associations between diabetes mellitus (DM), plasma glucose, forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), we analysed the results from a cross-sectional study of 11,763 subjects. The subjects were 20 yrs of age or older and were representative of the population of Copenhagen City. Two hundred and eighty four of the participants had DM as assessed by questionnaire. One hundred and seven subjects who did not report having DM had a plasma concentration of glucose higher than or equal to 11.1 mmol.l-1. In all age groups of diabetic subjects there was a slight impairment of lung function. It was more prominent in diabetic subjects treated with insulin than in subjects treated with oral hypoglycaemic agents and/or diet. Even in subjects without known DM, there was a significant association between reduction in lung function and raised plasma glucose concentration. On average, FVC (and FEV1) was reduced by 334 ml (and 239 ml) in diabetic subjects treated with insulin, and by 184 ml (and 117 ml) in diabetic subjects treated with hypoglycaemic agents and/or diet compared to control subjects.