tbuckley/cabot-search huggingface dataset:
Patterns of Intron Loss and Gain in Plants: Intron Loss-Dominated Evolution and Genome-Wide Comparison of O. sativa and A. thaliana
Authors: S. W. Roy, D. Penny
Journal: Molecular Biology and Evolution (2006)

Numerous previous studies have elucidated 2 surprising patterns of spliceosomal intron evolution in diverse eukaryotes over the past roughly 100 Myr. First, rates of recent intron gain in a wide variety of eukaryotic lineages have been surprisingly low, far too low to explain modern intron densities. Second, intron losses have outnumbered intron gains over a variety of lineages. For several reasons, land plants might be expected to have comparatively high rates of intron gain and thus to represent a possible exception to this pattern. However, we report several studies that indicate low rates of intron gain and an excess of intron losses over intron gains in a variety of plant lineages. We estimate that intron losses have outnumbered intron gains in recent evolution in Arabidopsis thaliana (roughly 12.6 times more losses than gains), Oryza sativa (9.8 times), the green alga Chlamydomonas reinhardtii (5.1 times), and the Bigelowiella natans nucleomorph, an enslaved green algal nucleus (2.8 times). We estimate that during recent evolution, A. thaliana and O. sativa have experienced very low rates of intron gain of around one gain per gene per 2.6–8.0 billion years. In addition, we compared 8,258 pairs of putatively orthologous A. thaliana–O. sativa genes. We found that 5.3% of introns in conserved coding regions are species-specific. Observed species-specific A. thaliana and O. sativa introns tend to be exact and to lie adjacent to each other along the gene, in a pattern suggesting mRNA-mediated intron loss. Our results underscore that low intron gain rates and intron number reduction are common features of recent eukaryotic evolution. This pattern implies that rates of intron creation were higher during earlier periods of evolution and further focuses attention on the causes of initial intron proliferation.
Autoantibody to the C3b/C4b receptor and absence of this receptor from erythrocytes of a patient with systemic lupus erythematosus.
Authors: J G Wilson, R M Jack, W W Wong, P H Schur, D T Fearon
Journal: Journal of Clinical Investigation (1985)

A 29-yr-old woman with systemic lupus erythematosus (SLE) was found to have no detectable C3b/C4b receptors (CR1) on her erythrocytes (E) when they were assayed by the binding of rabbit polyclonal and murine monoclonal (Yz-1) anti-CR1. Analysis by two-color fluorescent flow cytometry of CR1 expression on the patient's B lymphocytes that had been stained indirectly with monoclonal anti-B1 and rabbit F(ab')2 anti-CR1 also revealed a marked deficiency of CR1. Total cellular CR1 of neutrophils, assessed by a sandwich radioimmunoassay, was about half that of neutrophils from normal individuals. Because her E had expressed 173 sites/cell 2 yr before, the CR1 deficiency was considered to be acquired and a possible mechanism was sought. Autoantibody to CR1 was measured by a radioimmunoassay in which serum or its fractions were incubated in microtiter wells that had been coated with purified CR1, and binding of immunoglobulin to the wells was quantitated with 125I-labeled goat IgG antihuman F(ab')2. The CR1-specific binding of immunoglobulin from the patient's serum was 19.1 ng/well of the detecting antibody when her E had eight CR1 sites per cell; that of 28 healthy donors was 1.3 +/- 0.5 ng/well (mean +/- SEM), and that of 34 additional patients with SLE was 0.5 +/- 0.3 ng/well. The activity was present also in purified IgG and its F(ab')2 fragment, indicating that the binding of serum immunoglobulin to CR1 was not mediated by C3 fragments. The specificity of the patient's IgG for CR1 was confirmed when pretreatment of the CR1-coated wells with affinity-purified rabbit F(ab')2 anti-CR1 was shown to inhibit by 68% the binding of the IgG. The autoantibody also interacted with CR1 in cell membranes, as assessed by its capacity to inhibit the binding of indirectly fluoresceinated Yz-1 to neutrophils, and, when combined with goat IgG antihuman F(ab')2, to diminish the binding of dimeric C3b to normal E. During the period of the marked deficiency of CR1 the patient experienced an exacerbation of disease activity which was treated with prednisone. Clinical improvement was accompanied by a decrease in the serum concentration of anti-CR1 to levels present 2 yr earlier, and an increase of CR1 to 170 sites/E. The temporal association between high titers of an autoantibody to CR1, absence of CR1 from E, and heightened activity of SLE suggest that the former may have had a role in the other manifestations of the patient's disease.
The Physiologic Response of Schizophrenic and Other Psychotic Patients to a Standard Emotional Stress
Authors: George M. Perrin, Mark D. Altschule
Journal: New England Journal of Medicine (1957)

"WITHDRAWAL from reality" is often alleged to be the fundamental disorder in schizophrenia. Patients with this disease are considered to have suffered such severe emotional trauma that they retreat from further worldly contact into a self-made realm of fantasy. Many authors have further stated that these patients' apparent lack of psychologic reaction to external stimuli, physical or psychologic, is accompanied by diminished physiologic responsiveness, chiefly in functions that are mediated by the autonomie nervous system.The current study was undertaken to test the latter hypothesis – that schizophrenic patients show less physiologic response to emotional stress. The threatening stimulus used . . .
Flow cytometric assessment of hematopoietic cell subsets in cryopreserved preterm and term cord blood, influence of obstetrical parameters, and availability for transplantation
Authors: Aurea Cervera, Rosa Lillo, Félix García-Sánchez, Luis Madero, Rosario Madero, José L. Vicario
Journal: American Journal of Hematology (2006)

The aim of this study was to characterize the lymphocyte and the hematopoietic stem and progenitor cell (HPC) subsets of cryopreserved premature cord blood (PCB) compared to term cord blood (TCB) by flow cytometry, to study the influence of birth conditions, and to assess its availability for transplantation.Four-color flow cytometric analysis was performed on 43 PCB and 40 TCB cryopreserved samples using a panel of 24 different mAbs, directed against lymphoid and HPC surface markers. The CB volume was estimated by the weight of the newborn to determine the absolute MNC and CD34(+) cell content/CB sample. Clinical and obstetrical data were recovered. Statistical comparisons and a multiple regression analysis were performed.No consistent differences were found in the mononuclear cell (MNC) or CD34(+) cell concentration (x10(6)/L) between PCB and TCB. The percentage of primitive HPC (CD34(+)CD38(-), CD34(+)CD38(-)CD90(-)HLA-DR(-), CD34(+)CD38(-)CD90(-)HLA-DR(+)) and primitive lymphoid progenitors (CD34(+)CD7(+), CD34(+)CD7(+)CD19(-)CD117(-)) were higher in PCB than in TCB. Correspondingly, TCB had an increased percentage of committed HPC. No sample of PCB contained >2 x 10(7) MNC/kg (and only 48% had >1 x 10(5) CD34(+) cells) for a recipient of 20 kg body wt, as the minimum threshold recommended for CB transplantation. Obstetrical factors modulated mainly lymphocyte subsets and fewer HPC subpopulations. Acute fetal distress increased CD34(+) cells, especially the immature subsets. Maternal treatment with dexamethasone and intrauterine growth retardation decreased CD3(+) cells. No other obstetrical factors played a detrimental effect on CB cells if used for transplantation.PCB is richer in immature cells both in lymphocyte and HPC populations, and its use for transplantation, at least in special cases, should be reconsidered.
Recommendations for sepsis management in resource-limited settings
Authors: Martin W. Dünser, Emir Festic, Arjen Dondorp, Niranjan Kissoon, Tsenddorj Ganbat, Arthur Kwizera, Rashan Haniffa, Tim Baker, Marcus J. Schultz
Journal: Intensive Care Medicine (2012)

To provide clinicians practicing in resource-limited settings with a framework to improve the diagnosis and treatment of pediatric and adult patients with sepsis. The medical literature on sepsis management was reviewed. Specific attention was paid to identify clinical evidence on sepsis management from resource-limited settings. Recommendations are grouped into acute and post-acute interventions. Acute interventions include liberal fluid resuscitation to achieve adequate tissue perfusion, normal heart rate and arterial blood pressure, use of epinephrine or dopamine for inadequate tissue perfusion despite fluid resuscitation, frequent measurement of arterial blood pressure in hemodynamically unstable patients, administration of hydrocortisone or prednisolone to patients requiring catecholamines, oxygen administration to achieve an oxygen saturation >90%, semi-recumbent and/or lateral position, non-invasive ventilation for increased work of breathing or hypoxemia despite oxygen therapy, timely administration of adequate antimicrobials, thorough clinical investigation for infectious source identification, fluid/tissue sampling and microbiological work-up, removal, drainage or debridement of the infectious source. Post-acute interventions include regular re-assessment of antimicrobial therapy, administration of antimicrobials for an adequate but not prolonged duration, avoidance of hypoglycemia, pharmacological or mechanical deep vein thrombosis prophylaxis, resumption of oral food intake after resuscitation and regaining of consciousness, careful use of opioids and sedatives, early mobilization, and active weaning of invasive support. Specific considerations for malaria, puerperal sepsis and HIV/AIDS patients with sepsis are included. Only scarce evidence exists for the management of pediatric and adult sepsis in resource-limited settings. The presented recommendations may help to improve sepsis management in middle- and low-income countries.
Psychological problems and childhood atopic eczema
Authors: W.K. Woo, A. Higgins, None Corbett, E.A. Bingham
Journal: British Journal of Dermatology (2003)

Journal Article Psychological problems and childhood atopic eczema Get access W.K. Woo, W.K. Woo Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar A. Higgins, A. Higgins Department of Clinical Psychology, Royal Victoria Hospital, Belfast, UK Search for other works by this author on: Oxford Academic Google Scholar Corbett, JR, Corbett, JR Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar E.A. Bingham E.A. Bingham Department of Dermatology Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 6, 1 June 2003, Page 1291, https://doi.org/10.1046/j.1365-2133.2003.05524_2.x Published: 01 June 2003
Birth Weight and Maternal Smoking
Authors: D. G. W. Clyne
Journal: BMJ (1959)

<h3>Objective.</h3> The Social Role Participation Questionnaire (SRPQ) assesses the influence of health on 11 specific roles and 1 general role along 4 dimensions. In this study, a shortened version of the SRPQ (s-SRPQ) was developed in patients with ankylosing spondylitis (AS) to facilitate data collection in clinical studies and practice. <h3>Methods.</h3> Using data from 246 patients with AS and population controls, the fit of each role to the different participation dimensions, the contribution of each role to the measurement precision, and the correlation between dimensions were evaluated using item response theory. Representation of the 3 participation chapters of the International Classification of Functioning, Disability, and Health was ensured. Reliability of each dimension of both versions of the SRPQ was compared by correlating scores to the Medical Outcomes Study Short Form-36 (SF-36) and the Satisfaction With Life Scale (SWLS), and by comparing ability to discriminate between patients and controls and between patients with low and high disease activity (Bath Ankylosing Spondylitis Disease Activity Index ≥ 4). <h3>Results.</h3> The s-SRPQ, which assesses participation across 6 social roles along 2 dimensions (physical difficulty and satisfaction with performance), was proposed. Both dimensions of the s-SRPQ were highly reliable (r ≥ 0.86) and were shown to have construct validity as indicated by a similar pattern of correlations with the SF-36 and SWLS as the original SRPQ dimensions. Both versions discriminated well between patients and controls and between patients with high versus low disease activity (relative validity ≥ 0.72). <h3>Conclusion.</h3> The s-SRPQ retains the measurement properties of the original SRPQ and seems useful for measuring the effect of AS on participation.
Medical Use of Marijuana
Authors: Richard Doblin, Mark A. R. Kleiman
Journal: Annals of Internal Medicine (1991)

Letters1 May 1991Medical Use of MarijuanaRichard Doblin, MPP, Mark A. R. Kleiman, PhDRichard Doblin, MPPSearch for more papers by this author, Mark A. R. Kleiman, PhDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-114-9-809_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: We surveyed oncologists to determine whether marijuana in smoked form has a "currently accepted medical use in treatment" to control nausea in patients receiving chemotherapy (1). That point is at issue in an ongoing administrative and legal dispute about whether marijuana in smoked form should be available by prescription along with synthetic THC in oral form (Marinol, Roxane Laboratories, Inc., Columbus, Ohio) (2), of which almost 100 000 doses were prescribed in 1989 (3).In September 1989, the administrator of the Drug Enforcement Administration (DEA) rejected a petition to "reschedule" marijuana in smoked form from Schedule 1...References1. AMA Council on Scientific Affairs. Marijuana: its health hazards and therapeutic potentials. J Am Med Assoc. 1981;246:1823-7. CrossrefGoogle Scholar2. Chang A, Shiling D, and Stillman R. Delta-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. Ann Intern Med. 1979;91:819-24. LinkGoogle Scholar3. Quarterly Report, December, 1988. Annual Report, December 1989. Somerville, New Jersey: Unimed Pharmaceuticals. Google Scholar4. 54 Federal Register 53767-53785. 29 December 1989:53784. Google Scholar5. Slater L. Marijuana: medicine or menace? Spinal Network. 1990; winter:44. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Richard Doblin, MPP; Mark A. R. Kleiman, PhDAffiliations: Harvard University, Kennedy School of Government Boston, MA 02138 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMedical Cannabis Pain Benefit, Risk and Effectiveness Perceptions Among Belarus Medical StudentsMedical Marijuana: Tribulations and TrialsScience signals a new understanding of marihuanaOther Agents: Phencyclidine, Marijuana, Hallucinogens, Inhalants, and AnticholinergicsMedical Use of MarijuanaSchwartz Richard H., MDAspergillosis and MarijuanaStuart M. Levitz, MD, Richard D. Diamond, MD 1 May 1991Volume 114, Issue 9Page: 809-810KeywordsChemotherapyDrug administrationDrugsMarijuanaNausea ePublished: 1 December 2008 Issue Published: 1 May 1991 PDF downloadLoading ...
Compression treatment for multiple sclerosis
Authors: O F Conran, J C Bignall
Journal: BMJ (1983)

histamine, and several enzymes.Unfortunately, the crude venom is so unstable that even when fractionated in the cold on Sephadex in the presence of Cleland's reagent, EDTA, or stabilising reagent, much of the initial chemical characterisation of the venom is lost, and the pharmacological properties are greatly altered.At room temperature the pharmacological activities are altered within an hour or so, and on heating both the pain producing fraction and that causing the cardiovascular deficit become ineffective.The effect of the venom on blood clotting phenomena is not clear.
Controversies in Management: Access should be denied
Authors: H Lavender
Journal: BMJ (1996)

“Patients have a right to expect that you will not disclose any personal information which you learn during the course of your professional duties, unless they give you permission. Without assurances about confidentiality, patients may be reluctant to give doctors the information they need in order to provide good care.”—General Medical Council, Duties of a Doctor.1 I believe that when doctors reveal information to insurance companies they destroy the trust that is essential for good medical care. When I receive a request from an insurance company for information about a patient, I feel uncomfortable. I know that the patient has given written consent, but does the patient have any choice? In order to buy a home, most of us need a mortgage and life insurance is usually a requirement for this. Is the patient really in a position to refuse to apply for life insurance? When an insurance company requests information from a doctor, these are the kinds of questions that are asked
Preconditioning delays Ca2+-induced mitochondrial permeability transition
Authors: L Argaud
Journal: Cardiovascular Research (2004)

Objective: We investigated whether ischemic preconditioning (PC) may modify mitochondrial permeability transition (MPT) pore opening. Methods: In protocol 1, New Zealand White rabbits underwent either no intervention (sham group) or 10 min of ischemia followed by 5 min of reperfusion, preceded (PC) or not (C; control) by one episode of 5 min of ischemia and 5 min of reperfusion. Rabbits were pretreated by either saline or the MPT pore inhibitor cyclosporin A (CsA), or its non-immunosuppressive derivative Cs29 (10 mg/kg, IV bolus). Hearts were harvested and mitochondria isolated for further assessment of Ca2+-induced MPT using a Ca2+-sensitive micro-electrode. In protocol 2, C and PC hearts underwent 30 min of ischemia and 4 h of reperfusion. They were pretreated either by saline, CsA or Cs29, as in protocol 1. Infarct size was assessed by triphenyltetrazolium, and apoptosis by TUNEL staining. Results: In protocol 1, the Ca2+ overload required to induce MPT pore opening was significantly higher in PC than in C hearts. CsA and Cs29 significantly increased the Ca2+ overload required for MPT pore opening. In protocol 2, mean infarct size averaged 25% of the risk region in CsA/Cs29 treated hearts versus 15% in PC and 55% in controls (P<0.05 vs. C, P = ns vs. PC). Cardiomyocyte apoptosis was significantly reduced by PC and cyclosporin treatment with a mean apoptotic index of less than 2% in either group versus more than 11% in controls. Conclusion: This suggests that delayed opening of MPT pore may play a major role in ischemic PC.
Abstract B24: Inhibition of mTOR induces multidrug resistance in B-progenitor acute lymphocytic leukemia
Authors: Thanh-Trang Vo, Mengrou Lu, Duc Nguyen, Brandon Lui, Sharmila Maylla, David Fruman
Journal: Cancer Research (2014)

Abstract In B-progenitor acute lymphocytic leukemia (B-ALL), the current chemotherapeutic regimen can effectively cure most patients. However, some patients like those with the Philadelphia chromosome (Ph+) often relapse. Many of these Ph+ and some Ph- B-ALL have elevated signaling through the PI3K/AKT/mTOR pathway. The cancer proliferation and survival driven by this pathway provides these cancers an advantage that likely contributes to survival after chemotherapy, resulting in a high rate of relapse. The goal of this project is to test inhibitors of the various components of the PI3K/AKT/mTOR pathway to determine how to combine them with current chemotherapy to enhance leukemia killing and prevent relapse. Our pilot studies using Annexin-V and PI staining revealed that upstream PI3K inhibition often sensitizes B-ALL cell lines to chemotherapy but, surprisingly, downstream mTOR inhibition induces multidrug resistance. Using a novel assay called BH3 profiling we have found that mTOR inhibition actually sensitizes cells to triggers of mitochondrial apoptosis but an unknown resistance mechanism reverses the effects of this sensitization. This resistance is observed when using rapamycin as well as active-site mTOR inhibitors (MLN-0128 and AZD8055). The degree of drug resistance upon mTOR inhibition varies with different chemotherapeutic agents. mTOR inhibition best protects cells from killing by methotrexate and is least protective when combined with daunorubicin. Future work will focus on identifying the mechanism of drug resistance induced by mTOR inhibition. Thus far, we have found that resistance does not correspond with the effects on cell cycle. Identifying and finding mechanisms of reversing this protective effect could potentially augment the effectiveness of inhibiting the PI3K/AKT/mTOR pathway. Our results will lead to a better understanding of how to best utilize PI3K pathway inhibitors in combination with standard chemotherapy as an option for high-risk B-ALL cases driven by oncogenic PI3K signaling. Citation Format: Thanh-Trang Vo, Mengrou Lu, Duc Nguyen, Brandon Lui, Sharmila Maylla, David Fruman. Inhibition of mTOR induces multidrug resistance in B-progenitor acute lymphocytic leukemia. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr B24.
QUANTITATIVE STUDIES OF HUMAN LEUKOCYTIC AND FEBRILE RESPONSE TO SINGLE AND REPEATED DOSES OF PURIFIED BACTERIAL ENDOTOXIN*
Authors: Richard C. Mechanic, Emil Frei, Maurice Landy, Willie W. Smith
Journal: Journal of Clinical Investigation (1962)

Bacterial endotoxins injected intravenously in small doses into animals and man produce, among other effects, a transient granulocytopenia fol- lowed by a marked granulocytosis (1-7).Sev- eral comprehensive reviews have recently ap- peared which deal with the wide spectrum of bio- logic effects of these substances, including their relationship to the pathogenesis of fever, the development of tolerance to repeated administration, and effects upon host resistance to bacterial in- fection (5, 8, 9).Recent studies utilizing radioisotopic cell-label- ing techniques have increased considerably the understanding of granulocyte kinetics.Athens and his associates estimate the total blood granu- locytes in man to be made up of nearly equal com- partments of circulating cells and cells marginated and sequestrated within the capillary bed (10).The granulocytic elements in the marrow which are no longer capable of proliferation consist of a reserve of mature cells and cells in various stages of maturation which has been estimated to number 20 to 70 times the total blood granulocytes (7, 11, 12).Craddock, Perry and Lawrence consider this marrow granulocyte reserve to be the source of the granulocytes that enter the circulation in response to leukocytopheresis (11) and endotoxin (1).Athens and co-workers have added evidence that the source of the endotoxin granulocytosis is the bone marrow (10).No appreciable return of granulocytes to the circulation from ex- travascular spaces has been demonstrated.Crad- dock and others have suggested that the magnitude of the increase in circulating granulocytes after endotoxin administration may relate directly to the size of the marrow granulocyte reserve and
Treatment for Adolescents with Depression Study (TADS)
Authors: B. Vitiello
Journal: BMJ (2008)

Lenzer’s article contains several incorrect statements about the Treatment for Adolescents with Depression Study (TADS), which was funded by the National Institute of Mental Health (NIMH) under a contract to Duke University Medical Center.1 2 The design of the study was not unilaterally chosen by the investigators at Duke University: it was selected by NIMH on the basis of the recommendations of …