tbuckley/cabot-search huggingface dataset:
Monoamine oxidase B is associated with γ-secretase in cultured neurons and in brain
Authors: Sophia Schedin Weiss, Birgitta Wiehager, Bengt Winblad, Susanne Frykman, Lars Tjernberg
Journal: Molecular Neurodegeneration (2013)

Background Monoamine oxidase B (MAOB) is a mitochondrial outer membrane protein that degrades monoamines such as dopamine. Thus, MAOB inhibitors are used to treat for instance Parkinson’s disease patients. MAOB inhibitors, however, have neuroprotective properties that are independent on the monoamine-degrading capabilities and it is possible that MAOB have additional unrevealed functions. In an affinity pulldown/mass spectrometric screen for potential regulators of APP processing, we found MAOB to be associated with g-secretase in membranes prepared from brain, and data from co-immunoprecipitation experiments supported this finding. siRNA experiments showed that reduced levels of MAOB resulted in reduced Ab production, with only minor effects on the release of Notch intracellular domain (manuscript in preparation). In the present study, we use the proximity ligation assay (PLA), which gives a fluorescent signal when two target proteins are less than 40 nm apart, to study the MAOBg-secretase interaction in primary neurons and brain.
Slow infusion of vincristine in the treatment of idiopathic thrombocytopenic purpura
Authors: Arumugam Manoharan
Journal: American Journal of Hematology (1986)

Abstract Ten patients with idiopathic thrombocytopenic purpura (ITP) were treated wtih vincristine (VCR), given as a slow infusion over a 4‐hr period, at weekly intervals for 4 weeks. The VCR therapy achieved a sustained recovery of platelet count in five patients with ITP of 2 weeks to 5 months duration; a transient recovery was observed in four patients with ITP of 6 months to 5 years duration. Therapy had no effect at all in one patient who had ITP of 10 years duration. Vincristine therapy appears to be therapeutically more beneficial when given as a slow infusion and can achieve sustained recovery of platelet count in patients with ITP of less than six months duration.
A Predictive Instrument to Improve Coronary-Care-Unit Admission Practices in Acute Ischemic Heart Disease
Authors: Michael W. Pozen, Ralph B. D'Agostino, Harry P. Selker, Pamela A. Sytkowski, William B. Hood
Journal: New England Journal of Medicine (1984)

Each year 1.5 million patients are admitted to coronary-care units (CCUs) for suspected acute ischemic heart disease; for half of these, the diagnosis is ultimately "ruled out." In this study, conducted in the emergency rooms of six New England hospitals ranging in type from urban teaching centers to rural nonteaching hospitals, we sought to develop a diagnostic aid to help emergency room physicians reduce the number of their CCU admissions of patients without acute cardiac ischemia. From data on 2801 patients, we developed a predictive instrument for use in a hand-held programmable calculator, which requires only 20 seconds to compute a patient's probability of having acute cardiac ischemia. In a prospective trial that included 2320 patients in the six hospitals, physicians' diagnostic specificity for acute ischemia increased when the probability value determined by the instrument was made available to them. Rates of false-positive diagnosis decreased without any increase in rates of false-negative diagnosis. Among study patients with a final diagnosis of "not acute ischemia," the number of CCU admissions decreased 30 per cent, without any increase in missed diagnoses of ischemia. The proportion of CCU admissions that represented patients without acute ischemia dropped from 44 to 33 per cent. Widespread use of this predictive instrument could reduce the number of CCU admissions in this country by more then 250,000 per year. (N Engl J Med 1984; 310: 1273–8.)
Evaluation of the BTA Tests for the Detection of Bilharzial Related Bladder Cancer: The Cairo Experience
Authors: Hussein M. Khaled, Hussein M. Khaled, Ibrahim Abdel-Salam, Ibrahim Abdel-Salam, Manar Abdel-Gawad, Manar Abdel-Gawad, Ayman Metwally, Ayman Metwally, Salwa El-Demerdash, Salwa El-Demerdash, Mounir El-Didi, Mounir El-Didi, Ahmed Morsi, Ahmed Morsi, Laura Ishak, Laura Ishak
Journal: European Urology (2001)
Dose-dependent inhibition of hepatic fibrosis in mice by a TGF-β soluble receptor: Implications for antifibrotic therapy
Authors: Yutaka Yata, Philip Gotwals, Victor Koteliansky, Don C. Rockey
Journal: Hepatology (2002)

Transforming growth factor (TGF) β isoforms (in particular, TGF-β1) play a central role in the fibrogenic response to injury in many organs, including the liver. Although TGF-β is clearly important in fibrogenesis, a number of issues related to therapeutic antagonism have emerged. For example, the long-term effect of TGF-β antagonism is unknown; furthermore, controversy exists as to appropriate levels of TGF-β inhibition. Therefore, we aimed to examine TGF-β in models of chronic liver injury and to determine whether an in vivo dose-response relationship exists for inhibition of TGF-β. Liver injury was induced in BALB/c mice by administering carbon tetrachloride for 4 or 8 weeks. TGF-β binding was inhibited with a soluble TGF-β type II receptor (STR) construct, administered intraperitoneally over a dose range of 4.0, 1.0, 0.4, or 0.1 mg/kg twice weekly during fibrogenesis. Fibrogenesis was assessed by measurement of type I collagen messenger RNA (mRNA) expression and by quantitative morphometric analysis. In the 4-week study, STR at concentrations of 4.0, 1.0, and 0.1 mg/kg reduced type I collagen mRNA expression by 31%, 49%, and 60% compared with immunoglobulin (Ig) G controls, respectively. In the 8-week study, lower concentrations of STR (0.1 mg/kg) also had the greatest effect on type I collagen mRNA expression. Quantitative morphometrics similarly showed that lower concentrations of STR were the most antifibrogenic. In conclusion, the results confirm the antifibrotic effect of inhibiting TGF-β in chronic hepatic wounding and, moreover, show that its in vivo effect in the mouse is dose dependent. Such findings have major translational implications for therapeutic strategies aimed at TGF-β.
Clinical significance of P46L and R92Q substitutions in the tumour necrosis factor superfamily 1A gene
Authors: N Ravet, S Rouaghe, C Dode, J Bienvenu, J Stirnemann, P Levy, M Delpech, G Grateau
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) has been associated with several mutations in the <i>TNF receptor super family 1A</i> (<i>TNFRSF1A</i>), including most cysteine substitutions. However, the nature of two substitutions, P46L and R92Q, remains a topic of discussion. The aim of this study was to assess the actual role of these two sequence variations in a series of patients with TRAPS. <b>Methods:</b> The main clinical data of 89 patients with TRAPS have been prospectively registered on a standard form. 84 patients or members of families with recurrent episodes of inflammatory symptoms spanning a period of more than 6 months and harbouring a <i>TNFRSF1A</i> mutation were studied. Clinical data have been analysed according to the nature of the mutation—P46L, R92Q or others. <b>Results:</b> P46L is often seen in patients from Maghreb and is associated with a mild phenotype. P46L appears as a polymorphism with a non-specific role in inflammation. R92Q is associated with a variable phenotype and presents as a low-penetrance mutation. Interpreting these results will require a comparison with clinical signs and genetic background.
Epidemiology of Life Events: Life Events and Psychiatric Disorders in the Sesto Fiorentino Study
Authors: Carlo Faravelli, Mario Catena, Alessandra Scarpato, Valdo Ricca
Journal: Psychotherapy and Psychosomatics (2007)

&lt;i&gt;Background:&lt;/i&gt; Although life events have been consistently reported as precipitating factors for most psychiatric disorders, there is no comprehensive investigation of the relationship between severe life events and psychiatric disorders in the general population. &lt;i&gt;Methods:&lt;/i&gt; This is a community-based study of psychiatric disorders among a cohort representative of adults in an Italian town. A total of 2,363 subjects out of 2,500 selected to be representative of the population living in Sesto Fiorentino, central Italy, were interviewed by their own general practitioner using the Mini International Neuropsychiatric Interview. Of the 613 subjects, 609 who resulted positive for any psychiatric disorders and 123 out of a random sample of 130 negatives were re-interviewed by the psychiatrists using the Florence Psychiatric Interview. The Florence Psychiatric Interview was used to explore each distinct psychiatric episode. Life events were recorded in detail by a specific interview. &lt;i&gt;Results:&lt;/i&gt; During the year prior to the onset of the first psychiatric disorder, 35.8% of cases suffered from at least a severe event, compared with 12.2% of non-cases during a comparable period (OR = 4.0, 95% CI = 2.3–7.1). The excess of life events occurred for almost all the diagnostic categories. The same results were reproduced even when only the ‘independent’ life events were considered. The distribution of the events through the 12 months taken into account showed an even distribution of events among non-cases, whereas there was a clear accumulation in the last 3 months prior to the onset of the pathology in the cases. &lt;i&gt;Conclusions:&lt;/i&gt; Life stress is one of the main precipitating factors of psychopathology.
Influence of glucose and insulin administration on the Achilles tendon reflex time.
Authors: M Zachmann
Journal: BMJ (1967)

Whether the changes of the Achilles tendon reflexogram in thyroid disorders and in diabetes mellitus are related to the adrenaline system requires further investigation. SUMMARYIn five normal subjects the Achilles tendon reflex time was prolonged by intravenous glucose and shortened by intravenous insulin administration.The effect of insulin was abolished when it was given after the application of propranolol.
On Superf tation
Authors: A. Henry
Journal: BMJ (1849)

CASES have, from time to time, occurred, which have induced many physiologists to assert the possibility of a woman again conceiving after shIe has become pregnant.The phenomenon thus produced has re- ceived the name of SUPERFETATION; and, although rare, it is worthy of consideration, both from the interest which is attached to it as a physiological occurrence, and from the possibility of its giving rise to medico-legal questions, affecting the reputation or welfare of the indivi- duals concerned.It is not my intention, however, to enter into any dis- cussion on the latter subject; and I will therefore merely quote the words of Capuron in illustration of its possible importance." Quoique cette question ne se presente pas frequemment, elle peut etre d'un grand interet sous le rapport de la medecine legale.Une veuve, apres etre ac._ouchee d'un premier enfant, peut accoucher quelque temps apres d'un second, dont les collateraux contestent la legitimite, parce qu'i]s n'ont aucune idee de la superfetation.I1 peut arriver encore que cette veuve se remarie bient6t apres ses relevailles, et qu'elle accouche, peu de temps apres ce second manage, d'un second enfant a terme et tre'sviable.11 s'agit alors de decider auquel des deux maris appartient le second enfant."L I purpose then to confine my observations to the consideration of Superfaetation as a physiological phenomenon.It will be impossible to entirely determine whether it actually took place in all the cases alleged to have occurred; but we may, from a careful ex- amination of these cases, and an impartial consiJe1ration of the opinions of the various authors who have written on the subject, be able to draw some probable inferences, while we are at the same time enabled to see more clearly what additional data are required for the perfect compre- hension of a subject so difficult of investigation.The occurrence of cases which gave rise to the theory of Superfceta- tion was not unnoticed by the ancients.A work 7rep K Iutoc has
NOTES ON FRACTURES OF THE LONG BONES WITHOUT DEFORMITY. THE SUBPERIOSTEAL TYPE OF FRACTURE IN THE YOUNG.
Authors: JAMES PORTER FISKE
Journal: JAMA (1900)

That fractures of the long bones often occur without deformity, and indeed without many of the usual signs of fracture, is well known; still the absence of the usual signs may lead to the overlooking of the principal lesion at the first examination, and when this has happened, the subsequent condition may be quite disastrous to the attending physician at the second examination. A study of the clinical features of simple fractures, combined with the findings of the operator, should enable the careful observer to make a rather accurate diagnosis in most of the bone lesions brought to his attention. Fractures without deformity may occur in the long bones at any age, but in adults these fractures are easily displaced and give the usual signs on examination. In children, loss of continuity without deformity has been noted in cases of epiphyseal separation, where there has been spontaneous reduction, or where
Infection of Arteriovenous Graft Fistulas
Authors: MELVIN YUDIS
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 May 1978Infection of Arteriovenous Graft FistulasMELVIN YUDIS, M.D., F.A.C.P.MELVIN YUDIS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-88-5-717_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The recent article by Dobkin and associates (1) emphasizes that antibiotic treatment alone is often successful in the treatment of arteriovenous fistula infections. They also mentioned that bovine heterograft arteriovenous fistulas more often lead to sepsis than did brescia arteriovenous fistulas. Most infections were due to staphylococci, and 25% were due to Gram-negative bacilli. Our recent experience suggests another type of infection can occur chronically in a clotted bovine heterograft fistula (2). Our patients who had clotted bovine fistulas had unsuccessful attempts at surgical declotting. After this operative declotting maneuver the patients developed chronic draining infections generally...References1. DOBKINMILLERSTEIGBIGEL JMN: Septicemia in patients on chronic hemodialysis. Ann Intern Med 88:28-33, 1978. LinkGoogle Scholar2. YUDISGLASERNORTH-COOMBES MBD: Chronic Staphylococcus epidermidis infection—a problem of clotted bovine heterograft AV fistulas (abstract). Am Soc Nephrol p. 42a, 1977. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Abington Memorial Hospital Abington, PA 19001 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1978Volume 88, Issue 5Page: 717-717KeywordsAntibioticsFistulasSepsisStaphylococcal infection Issue Published: 1 May 1978 PDF DownloadLoading ...
Noninvasive imaging oral absorption of insulin delivered by nanoparticles and its stimulated glucose utilization in controlling postprandial hyperglycemia during OGTT in diabetic rats
Authors: Er-Yuan Chuang, Kun-Ju Lin, Fang-Yi Su, Fwu-Long Mi, Barnali Maiti, Chiung-Tong Chen, Shiaw-Pyng Wey, Tzu-Chen Yen, Jyuhn-Huarng Juang, Hsing-Wen Sung
Journal: Journal of Controlled Release (2013)

This work examined the feasibility of preparing a pH-responsive nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with ethylene glycol tetraacetic acid (γPGA–EGTA) for oral insulin delivery in diabetic rats during an oral glucose tolerance test (OGTT). OGTT has been used largely as a model to mimic the period that comprises and follows a meal, which is often associated with postprandial hyperglycemia. Based on Förster resonance energy transfer (FRET), this work also demonstrated the ability of γPGA–EGTA to protect insulin from an intestinal proteolytic attack in living rats, owing to its ability to deprive the environmental calcium. Additionally, EGTA-conjugated NPs were effective in disrupting the epithelial tight junctions, consequently facilitating the paracellular permeation of insulin throughout the entire small intestine. Moreover, results of positron emission tomography and computer tomography demonstrated the effective absorption of the permeated insulin into the systemic circulation as well as promotion of the glucose utilization in the myocardium, and skeletal muscles of the chest wall, forelimbs and hindlimbs, resulting in a significant glucose-lowering effect. Above results indicate that as-prepared EGTA-conjugated NPs are a promising oral insulin delivery system to control postprandial hyperglycemia and thus may potentially prevent the related diabetic complications.
Studies of intestinal lymphoid tissue. I. Electron microscopic evidence of 'blast transformation' in epithelial lymphocytes of mouse small intestinal mucosa.
Authors: M N Marsh
Journal: Gut (1975)

The morphology of epithelial lymphocytes in osmium-fixed, Epon-embedded jejunum of adult mice was studied by light and electron microscopy. Toluidine blue-stained 1 mum 'thick' plastic sections were compared with adjacent thin sections, thereby permitting precise ultrastructural identification and description of selected epithelial lymphocytes. Their size and appearances varied considerably, ranging from typical small lymphocytes through medium-sized lymphocytes to large immunoblasts. A high proportion of medium-sized epithelial lymphocytes (mean diameter 6-9 +/- 1-1 mum) contained several lysosomes, extensive Golgi complexes, prominent centrioles and abundant ribosomes. Their appearances, therefore, corresponded directly to mitogen-stimulated lymphocytes. In contrast, immunoblasts were big cells (mean diameter 11-0 +/- 0-8 mum) with large, euchromatic nuclei and prominent nucleoli. The majority had pale-staining, ribosome-studded cytoplasm and thus resembled type I, or T blasts. Very rarely, densely staining blasts containing ribosomes and well developed rough endoplasmic reticulum were observed; these corresponded to type II or B blasts. These observations indicate that transformation of lymphocytes occurs within the interepithelial cell spaces of the small intestinal mucosa, suggesting that epithelial lymphocytes are immunocompetent cells which may be responsive to local antigenic stimulation.
Absorption of Methotrexate And Hepatotoxicity
Authors: Howard V. Dubin
Journal: JAMA (1969)

To the Editor:—  Recently interest has been aroused in hepatotoxicity in psoriasis patients with methotrexate. 1,2 One factor which may be of importance in the development of hepatotoxicity is the rate of intestinal absorption of the drug.  Freeman-Narrod 3 showed that there were at least two distinct patterns of intestinal absorption of methotreaxate. The first pattern showed quite slow absorption, with low peak blood levels and slow clearing from the blood. The second pattern showed rapid absorption with high peak blood levels and rapid clearing. In addition, after several weeks of treatment, in many of the patients with the second (rapid) absorption pattern, the absorption curve altered in such a way that they became slow absorbers.  The same author 3 also showed that the patient who retained a rapid methotrexate absorption pattern throughout the course of therapy did not develop signs of toxic effects. Those who were slow absorbers, or
Utility of Early Screening Magnetic Resonance Imaging for Extensive Hip Osteonecrosis in Pediatric Patients Treated With Glucocorticoids
Authors: Sue C. Kaste, Deqing Pei, Cheng Cheng, Michael D. Neel, W. Paul Bowman, Raul C. Ribeiro, Monika L. Metzger, Deepa Bhojwani, Hiroto Inaba, Patrick Campbell, Jeffrey E. Rubnitz, Sima Jeha, John T. Sandlund, James R. Downing, Mary V. Relling, Ching-Hon Pui, Scott C. Howard
Journal: Journal of Clinical Oncology (2015)

Purpose Hip osteonecrosis frequently complicates treatment with glucocorticoids. When extensive (affecting ≥ 30% of the epiphyseal surface), 80% of joints collapse within 2 years, so interventions are needed to prevent this outcome. Patients and Methods This prospective cohort magnetic resonance imaging (MRI) screening study included all consecutive children treated for acute lymphoblastic leukemia on a single protocol. Hip MRI was performed at 6.5 and 9 months from diagnosis (early screening) and at completion of chemotherapy (final evaluation) to determine whether screening could identify extensive hip osteonecrosis before symptom development. Results Of 498 patients, 462 underwent screening MRI. Extensive asymptomatic osteonecrosis was identified by early screening in 26 patients (41 hips); another four patients (seven hips) were detected after the screening period, such that screening sensitivity was 84.1% and specificity was 99.4%. The number of joints screened to detect one lesion was 20.1 joints for all patients, 4.4 joints for patients older than 10 years, and 198 joints for patients ≤ 10 years old (P &lt; .001). Of the 40 extensive lesions in patients older than 10 years, 19 required total hip arthroplasty and none improved. Of eight extensive lesions in younger patients, none required arthroplasty and four improved. Conclusion In patients age 10 years old or younger who require prolonged glucocorticoid therapy, screening for extensive hip osteonecrosis is unnecessary because their risk is low and lesions tend to heal. In children older than 10 years, early screening successfully identifies extensive asymptomatic lesions in patients who would be eligible for studies of interventions to prevent or delay joint collapse.
Key Factors in the Development of Asthma: Atopy
Authors: PATRICK G. HOLT
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

One approach to unraveling the role of the multiple risk factors that contribute to the development of asthma is to track the process in cohorts of children from birth until age(s) at which the disease manifests. In relation to atopy, this involves the prospective and cross-sectional study of allergen-specific T cell function in cohorts of children, focusing particularly on responses to the major inhalant allergens that have been identified as asthma triggers in later life. The key issues in this context are ( 1 ) what factor(s) are responsible for the polarization of allergen-specific helper T cell memory toward the atopyassociated helper T cell type 2 (Th2) cytokine phenotype, and ( 2 ) why does the development of this form of helper T cell memory lead to the development of asthma in some but not all individuals with atopic asthma.