tbuckley/cabot-search huggingface dataset:
Regulation of Stat3 nuclear export
Authors: Samita Bhattacharya, Christian Schindler
Journal: Journal of Clinical Investigation (2003)

Stat3 is the most pleiotropic member of the signal transducer and activator of transcription (STAT) family of transcription factors and mediates pivotal responses for the cytokine family. In resting cells, STATs, including Stat3, reside largely in the cytoplasm. Upon cytokine stimulation, they rapidly translocate to the nucleus, where they promote the expression of target genes. During the subsequent period of signal decay they are re-exported back to the cytoplasm in preparation for the next round of signaling. This process of nuclear export can be blocked by the fungal toxin leptomycin B (LMB). In contrast to what appears to be the case for Stat1, LMB treatment not only blocks the poststimulation export of Stat3 from the nucleus back to the cytoplasm, but also promotes the nuclear accumulation of Stat3 in resting cells. Remarkably, the LMB-dependent nuclear accumulation of Stat3 in resting cells is independent of tyrosine phosphorylation, highlighting the existence of a "basal" signaling pathway. Subsequent studies identified three nuclear export signal (NES) elements. Two of these elements, Stat3306–318 and Stat3404–414, corresponded to those recently identified in Stat1, and a third, Stat3524–535, is novel. Stat3306–318 appears to be important in the rapid nuclear export seen after stimulation (poststimulation export), whereas the Stat3404–414 and Stat3524–535 play a more important role in regulating basal nuclear export. In summary, these studies indicate that the process of Stat3 nuclear export is dependent on multiple NES elements.
Methacholine responsiveness using the raised volume forced expiration technique in infants.
Authors: M J Hayden, S G Devadason, P D Sly, J H Wildhaber, P N LeSouëf
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Infant lung function can be assessed with the tidal volume "squeeze" technique or, over an extended volume range, with the newer raised volume forced expiration technique (RVFET). We assessed methacholine responsiveness in 11 infants, measuring both maximal expiratory flow at functional residual capacity (V.max,FRC)with the tidal volume technique, and forced expiratory volume/time (FEV(t)) with RVFET. We used a standard methodology for the former. FEV(t) was measured by inflating the infant's lungs to 20 cm H2O and forcing expiration using a jacket setup to transmit a pressure of 20 cm H2O to the airway. Lung function was measured at baseline and after methacholine inhalations, increasing from 0.1 g/L to 10 g/L in half log dosage increments (DI). The provocative concentrations (PC) of methacholine leading to a 40% fall in V.max,FRC and a 15 or 20% fall in FEV(t) were calculated. The mean provocative concentration of methacholine required to produce a 40% fall in V.max,FRC was less than that required to produce a 20% fall in FEV0.5 by 0.39 DI (95% CI, -0.60 to 1.38) and less than that required to produce a 20% fall in FEV0.75 by 0.42 DI (95%, CI, -0.54 to 1.39). Similarly, the provocative concentration of methacholine required to produce a 40% fall in V.max,FRC was less than that required to produce a 15% fall in FEV0.5 by 0.14 DI (95% CI, -0.99 to 1.28) or a 15% fall in FEV0.75 by 0.13 DI (95% CI, -0.80 to 1.08), but the differences were small and not significant. Despite these differences the agreement between the two methods was good, and bronchoconstriction was not attenuated by the forced inspiration delivered by the raised volume maneuver. We conclude that the raised volume forced expiration technique is able to detect methacholine-induced bronchoconstriction.
Psychotherapeutic Treatments Evaluated with Two Instruments: Clinical Questionnaire and Semantic Differential
Authors: Jean Bovet, Jacques Spagnoli, Edmond Gilliéron
Journal: Psychotherapy and Psychosomatics (1991)

We evaluated about 100 psychotherapeutic treatments on the Freudian model with two independent instruments: a clinical questionnaire (assessed globally and intuitively) and a semantic differential (processed through various mathematic analyses). The results obtained with the two instruments were compared, and we also compared the semantic evolution of patients with that of normal subjects. Both instruments show an undeniable average improvement among patients. The semantic differential also shows that the various 'zones' tested by the inducive words are neither equally affected by neurosis nor equally modified by treatment.
Immunofluorescent Localization of Antihemophilic Factor Antigen and Fibrinogen in Human Renal Diseases
Authors: John R. Hoyer, Alfred F. Michael, Leon W. Hoyer
Journal: Journal of Clinical Investigation (1974)

Tissue localization of antihemophilic factor (AHF, factor VIII) antigen and fibrinogen by immunofluorescent microscopy was determined in 146 specimens of normal and diseased kidneys. AHF antigen was present in the endothelial cells of glomeruli, peritubular capillaries, arteries, and veins of normal kidneys; a distribution similar to that in other tissues. In scleroderma and malignant hypertension, deposition of AHF antigen and fibrinogen was limited to the markedly thickened endothelial layers of arteries. More extensive intense deposition of both AHF antigen and fibrinogen in glomeruli and in arterial walls were present in hyperacute renal homograft rejection, hemolyticuremic syndrome, postpartum renal failure, and in some cases of acute homograft rejection. In contrast, deposition of fibrinogen was observed in glomerular epithelial cresents in severe proliferative glomerulonephritis, but AHF deposition was not present in these lesions. Glomerular deposition of fibrinogen without increased AHF standing was also detected in renal tissue from patients with anaphylactoid purpura nephritis and in recurrent macroscopic hematuria with focal glomerulonephritis. Increased staining of peritubular capillaries with anti-AHF was seen in diseased kidneys irrespective of etiology. Immunofluorescent localization of AHF, a participant in the intrinsic coagulation pathway, offers a new way by which to analyze the mechanisms responsible for fibrinogen deposition in disease.
Cerebral Commissurotomy
Authors: J. E. Bogen
Journal: JAMA (1965)

THE SIZE and the location of the corpus callosum and anterior commissure suggest an important role in propagation of seizures from one side of the brain to the other. In 1940, Van Wagenen and Herren<sup>1</sup>cut the corpus callosum to various extent in two dozen patients; only one had complete section of both corpus callosum and anterior commissure. The subsequent report by Akelaitis<sup>2</sup>on these patients indicates that a number of them were improved. Complete section of corpus callosum and anterior commissure was therefore offered to an apparently hopeless epileptic having one to three generalized convulsions per week, with best medical control.<sup>3</sup>He has not had a generalized convulsion since that operation (Feb 6, 1962). Furthermore, although deficits in interhemispheric integration could be demonstrated under specialized testing conditions,<sup>4</sup>the patient's well-being and general behavior were improved. Because of his excellent response, five more patients underwent this
Randomized Phase III Trial on Gemcitabine Versus Mytomicin in Recurrent Superficial Bladder Cancer: Evaluation of Efficacy and Tolerance
Authors: Raffaele Addeo, Michele Caraglia, Sergio Bellini, Alberto Abbruzzese, Bruno Vincenzi, Liliana Montella, Antonio Miragliuolo, Rosario Guarrasi, Michele Lanna, Gregorio Cennamo, Vincenzo Faiola, Salvatore Del Prete
Journal: Journal of Clinical Oncology (2009)

Purpose Approximately 30% to 40% patients with a superficial bladder cancer treated with Bacille Calmette-Guerin (BCG) or epirubicin do not respond; of the initial responders, 35% have a relapse within 5 years. We compare the therapeutic efficacy and toxicity of intravescical infusions of gemcitabine (GEM) with mitomycin (MMC) in patients with a recurrent superficial bladder cancer. Patients and Methods Patients with a history of a previously treated, recurrent Ta-T1, G1-G3 bladder transitional cell carcinoma were enrolled in the study. The patients received a 6-week course of GEM infusions or 4-week course of MMC. In both arms, for the initial responders who remained free of recurrences, maintenance therapy consisted of 10 monthly treatments during the first year. Results A total of 120 patients were enrolled and randomly assigned to either the MMC or GEM treatment arm. At the end of the study, 109 patients (55 in MMC and 54 in GEM) were assessable. The median duration of follow-up was 36 months for either arm. In the GEM arm, 39 (72%) of 54 patients remained free of recurrence versus 33 (61%) of 55 in MMC arm. Among patients with recurrences, 10 in the MMC arm and six in the GEM arm also had a progressive disease by stage. The incidence of chemical cystitis in the MMC arm was statistically higher than in the GEM arm (P = .012). Conclusion This study demonstrates that GEM has better efficacy and lower toxicity than MMC; therefore, GEM appears as a logical candidate for intrabladder therapy in patients with refractory transitional cancer.
Introductory Address Delivered at the Medical School of the London Hospital
Authors: A. Clark
Journal: BMJ (1876)

views with which some of them may be regarded, it must be admitted INTRODUCTORY ADDRESS that, in the main, they tend to promote the attainment of the objects for which these institutions exist.But it is not pretendled that those DELIVERED AT changes have yet enabled us to achieve an entire success.It has been THE MEDICAL SCHOOL OF THE LONDON ~~felt and confessed that there is still room to make our education more THE MEDICAL SCHOOL OF THE LONDON ~~efficient and complete, and to adjust our ample meanis wvith more ex- actitude to the varying wants and capabilities of individual students. HOSPITAL,WVe have, therelfore, effected recently an important and crucial change At the O.Pening of the Session, 1876177.in the constitution of the College.Upon conditions which need not now be specified, because they cannot now be here discussed, its By A ND R EW C LA RK, M
Juvenile elastoma and osteopoikilosis (the Buschke-Ollendorff syndrome)
Authors: J. G.L. MORRISON, E. WILSON JONES, D. M. MACDONALD
Journal: British Journal of Dermatology (1977)

Sixteen patients from seven different families with the Buschke-Ollendorff syndrome have been studied. Osteopoikilosis was found in two-thirds of the patients radiologically examined and all but two had skin involvement. The predominant clinical pattern consisted of grouped skin coloured papules and discs that were distributed asymmetrically and which usually had presented at an early age. The skin lesions showed the characteristic histological changes of juvenile elastoma which, it is suggested, is the specific dermatological abnormality of the Buschke-Ollendorff syndrome.
Milestones in the biology and pharmacology of histamine H<sub>1</sub>-receptor antagonists
Authors: Gianni Marone
Journal: Allergy (1997)

Daniele Bovet's pioneering discovery that a series of compounds possessing anti‐histamine activity reduced the symptoms of anaphylaxis provided the proof that histamine plays a pivotal role as a mediator of allergic reactions. Basophils and mast cells are the major sources of histamine in man and they are thus one of the primary effector cells of allergic inflammation. Some H 1 ‐receptor antagonists posseses a variety of antiinflammatory activity to H 1 ‐ ‐ antagonism in vitro and in vivo . This promising area should be explored further and much remains to be done in the evaluation of the immunodulatory effects of anti‐histamines.
A Surgical Curtain Call
Authors: Alexander J. Walt
Journal: JAMA (1991)

In early 1952, Margot Fonteyn was recovering from a leg injury that had threatened her career. Already famous at 33, she felt her future uncertain as she fought her way back through physiotherapy and exercise. Fonteyn, after her recent close contact with surgeons, was fascinated by the many aspects of their work and the manner in which they trained for their careers. She understood intuitively the linkage between their daily grind, which she saw as equivalent to her repetitious exercises at the barre, and their preparations for major performances with death as the audience, which tested their stamina, inner resources, surgical choreography, and confidence born of training. She was convinced that surgery could not be dissociated from theater and a sense of grace. I was a resident when I met Margot Fonteyn on a foggy Sunday afternoon in what was still a depressed postwar London. How we both arrived at
Factors Affecting the Incidence and Severity of Poliomyelitis
Authors: William J. Dougherty, Stanley N. Faro
Journal: New England Journal of Medicine (1959)

THE incidence of poliomyelitis in New Jersey has varied widely over nearly half a century. In 1916 more than 4000 cases were reported within the State, with a death rate of 40.3 per 100,000. Other major epidemics occurred in 1931, 1945 and 1949. On the other extreme, there have been twelve years since 1916 in which attack rates of 2.0 per 100,000 and lower were recorded, associated with a death rate of 0.5 and lower. In 1957, 81 cases occurred, with no deaths, the only year since 1916 in which no fatal cases were reported.In 1958, however, there was . . .
Telomere Repeat Binding Factor 2 Interacts with Base Excision Repair Proteins and Stimulates DNA Synthesis by DNA Polymerase β
Authors: Meltem Muftuoglu, Heng Kuan Wong, Syed Z. Imam, David M. Wilson, Vilhelm A. Bohr, Patricia L. Opresko
Journal: Cancer Research (2006)

The ends of linear chromosomes are capped and protected by protein-DNA complexes termed telomeres. Consequences of telomere dysfunction include genomic instability that can contribute to neoplastic transformation and progression. Telomere binding proteins interact with numerous proteins involved in DNA repair, underscoring the importance of regulating DNA repair pathways at telomeres. Telomeric DNA is particularly susceptible to oxidative damage, and such damage is repaired primarily via the base excision repair (BER) pathway. Using a screen for potential interactions between telomere repeat binding factor 2 (TRF2) and proteins involved in BER of oxidized bases in vitro, we found that TRF2 physically bound DNA polymerase beta (Pol beta) and flap endonuclease 1 (FEN-1). The interactions with endogenous proteins in human cell extracts were confirmed by coimmunoprecipitation experiments. The primary binding sites for both Pol beta and FEN-1 mapped to the TRF2 NH2-terminal and COOH-terminal domains. We further tested the ability of TRF2 to modulate BER protein partners individually on a variety of substrates in vitro. TRF2 stimulated Pol beta primer extension DNA synthesis on telomeric and nontelomeric primer/template substrates, resulting in up to a 75% increase in the proportion of longer products. TRF2 also stimulated Pol beta strand displacement DNA synthesis in reconstituted BER reactions and increased the percent of long-patch BER intermediates on both telomeric and nontelomeric substrates. Potential roles of TRF2 in cooperation with BER proteins for DNA repair pathways at telomeres, as well as other genomic regions, are discussed.
Predictors of success after isolation of pulmonary veins for atrial fibrillation
Authors: Hakan Oral, Bradley P. Knight, Hiroshi Tada, Aman Chugh, Sohail Hassan, Christoph Scharf, Radmira Greenstein, Mehmet Ozaydin, Frank Pelosi, S.Adam Strickberger, Fred Morady
Journal: Journal of the American College of Cardiology (2002)
Adherence to asthma therapy in the preschool child
Authors: C. S. Rand
Journal: Allergy (2002)

Preschool children's adherence to asthma therapy is often sub‐optimal and can result in decreased quality of life for children and parents, as well as an increased risk for dangerous asthma exacerbations. Asthma management for the preschool child presents some unique challenges to adherence to therapy, including the child's limited ability to communicate, multiple caregivers responsible for medications, and parental concerns about medications. Parent beliefs, characteristics of the regimen, and family functioning have been associated with adherence levels. Understanding and improving adherence to asthma therapy for the preschool child will necessarily require addressing these age‐specific concerns.
Alteration in the control of mitochondrial respiration by outer mitochondrial membrane and creatine during heart preservation
Authors: L Kay
Journal: Cardiovascular Research (1997)

Objective: This study aimed to evaluate the nature and extent of mitochondrial alterations during heart preservation. Methods: Rat hearts, isolated after cardioplegia in situ, were preserved for 6 or 15 h at 4°C either by immersion in cardioplegic solution or by low-flow perfusion (0.3 ml/min) with cardioplegic solution. The energy state of hearts at the end of preservation was determined by 31P-NMR spectroscopy and functional recovery was evaluated on reperfusion. Variables of mitochondrial respiration (maximal rate of respiration in the presence of ADP=ΔVmax, apparent Km for ADP, effect of creatine) were evaluated on skinned fibers and compared with those determined in controls and in hearts subjected to 1 hour of ischemia at 37°C. Results: Serious mitochondrial alterations were detected in fibers from 15 h immersed hearts: decrease of ΔVmax and of apparent Km for ADP, loss of the stimulatory effect of creatine, and disruption of the outer mitochondrial membrane. The extent of alterations was more accentuated in fibers from normothermic ischemic hearts, in which some damage of the inner mitochondrial membrane also occured. In fibers from hearts preserved for 6 h, no significant changes in mitochondrial variables could be detected. When the hearts were preserved under low-flow perfusion for 15 h, only the stimulatory effect of creatine on respiration was significantly decreased. The extent of the loss of the stimulatory effect of creatine paralleled the accumulation of inorganic phosphate (Pi) during preservation and the decrease in left ventricular function on reperfusion. Conclusions: Alterations related to the outer membrane and the intermembrane space are among the earliest signs of damage to mitochondrial function during heart preservation. These alterations could be attributed to the swelling of mitochondria under the effect of Pi. The determination of mitochondrial parameters in biopsy samples could allow a simple and rapid evaluation of energy-producing and transfer capacities of the myocardium.
Further evidence for recessive inheritance of von willebrand disease with abnormal binding of von willebrand factor to factor VIII
Authors: M. F. Lopez‐Fernandez, M. J. Blanco‐Lopez, M. P. Castiñeira, J. Batlle
Journal: American Journal of Hematology (1992)

Abstract A new family with a bleeding diathesis and FVIII deficiency secondary to abnormal binding of von Willebrand factor (vWF) to factor VIII (FVIII) is described. Two propositi of this family, an 18‐year‐old male and a 33‐year‐old female, both with a history of epistaxis, bruising, bleeding from the gums, epistaxis, hemarthrosis, and hematoma, were analyzed. Also additional members of the same family with no bleeding history were also studied. The propositi showed normal vWF activities, low FVIII activity; one of them had been diagnosed as having hemophilia A and the other was a hemophilia A carrier. Both showed a very poor response to treatment with FVIII concentrates and desmopressin (DDAVP) but a good clinical response to cryoprecipitate. APTT was prolonged and no inhibitory activity was noticeable in their plasmas. Thirty‐five units per kilogram body weight of Hemofil M was infused to both propositi and FVIII reached basal level within 60 minutes of the infusion. No FVIII response at all was observed in the female after intravenous DDAVP administration. However, the male who received the infusion of 35 U/kg body weight of Humate‐P achieved a normal FVIII level that was maintained for 12 hours. Multimeric analysis of vWF was normal in all the members studied. Von Willebrand factor domain for FVIII binding was assayed in the two propositi and in six other members of the same family by using a non‐isotopic and sensitive method, a modification of the one previously described, using the Hemofil M concentrate as exogenous FVIII. The data obtained showed that both propositi had similar binding to that observed by using plasma of a patient with severe von Willebrand disease. Furthermore, five siblings had a decreased binding of vWF to FVIII, when compared with plasma from normal individuals or patients with hemophilia A. We also observed that, for screening purpose, the ratio of bound FVIII/immobilized vWF (at saturation of the anti‐vWF and offering of 1 U/ml of exogenous FVIII) distinguished two levels of abnormality (normal range 0.70–1.15, propositi 0,004–0.007, and remaining members affected 0.25–0.42). The most probable explanation is that the propositi are homozygous or double heterozygous, the other five siblings affected being heterozygous for a recessive vWF defect. This more accessible assay presented here may be of help in routine analysis for diagnosing this type of von Willebrand disease, which has important implications for therapy and genetic counseling. © 1992 Wiley‐Liss, Inc.
The Gastroenterologist: A Review Journal for Practitioners
Authors: Stuart Chen
Journal: JAMA (1995)

Gastroenterology and hepatology are rapidly evolving and expanding fields that cover many diverse human diseases of common occurrence such as peptic ulcer, cholelithiasis, and viral hepatitis. Despite the fact that there are many gastroenterology journals available, practitioners in the field often have difficulty bringing together useful information from them because of the journals' research or review orientation. Described in the foreword of the first issue as "a journal for the future,"<i>The Gastroenterologist</i>presents practical information in a manner designed to assist physicians with patient care and to contribute to their continuing education. The journal is divided into five subject sections representing traditional anatomic divisions: esophageal and gastric diseases; pancreatic and biliary diseases; liver diseases; small intestine, nutrition, and malabsorption; and the colon, particularly relating to inflammatory bowel disease and infectious diseases. Four other sections include new techniques, therapeutic recommendations, grand rounds, and a cover biography. The eight section editors
Mesenchymal Tumor in the Calcaneus With Oncogenic Osteomalacia: A Case Report
Authors: Joyce Chermikoski Ozawa, Ana Flávia Nóbrega de Paiva, José Donato de Próspero, Osmar Monte, Nilza Maria Scalissi, Sérgio Setsuo Maeda
Journal: Journal of Clinical Oncology (2010)