tbuckley/cabot-search huggingface dataset:
Cardiovascular Events and Geriatric Scale Scores in Elderly (70 Years Old and Above) Type 2 Diabetic Patients at Inclusion in the GERODIAB Cohort
Authors: Bernard Bauduceau, Jean Doucet, Jean-Pierre Le Floch, Christiane Verny
Journal: Diabetes Care (2013)

OBJECTIVE To analyze the relationships between cardiovascular complications and geriatric scale scores in French elderly (≥70 years of age) type 2 diabetic patients at inclusion in the GERODIAB cohort. RESEARCH DESIGN AND METHODS GERODIAB is the first French multicenter, prospective, observational survey designed to analyze the influence of glycemic control on morbidity/mortality in type 2 diabetic patients aged ≥70 years during a 5-year follow-up period. This study analyzed the relationships between classical macroangiopathic complications and geriatric scale scores in 987 patients at baseline, using bivariate and multivariate analyses. RESULTS Cardiac ischemia (31.2%) was significantly associated with impaired activities of daily living (ADL) scores (P < 0.001). Stepwise logistic regression included hypercholesterolemia, ADL, sex, and hypertension successively (70.3% concordance; P < 0.001). Heart failure (10.1%) was associated with impaired Mini Mental State Examination (MMSE), instrumental ADL (IADL) (P < 0.05), and ADL scores (P < 0.001). With the logistic model, waist circumference, age, and HDL cholesterol were significant factors (70.7% concordance; P < 0.001). Arterial disease of the lower limbs (25.6%) was associated with impaired IADL and ADL scores (P < 0.001). Significant factors using the logistic model were duration of diabetes, IADL score, hypertension, and sex (62.8% concordance; P < 0.001). Cerebral ischemia (15.8%) was associated with impaired MMSE, Mini Nutritional Assessment, ADL, and IADL scores (P < 0.01). IADL, sex, hypertension, and ADL were included in the logistic model successively (65.6% concordance; P < 0.001). CONCLUSIONS In this specific population, impaired geriatric scale scores were found to be associated with classical macrovascular complications, notably using multivariate analyses. This suggests the benefits of thorough screening and management of cognitive and functional decline in elderly type 2 diabetic patients.
Preferential DNA repair in expressed genes.
Authors: P C Hanawalt
Journal: Environmental Health Perspectives (1987)

Potentially deleterious alterations to DNA occur nonrandomly within the mammalian genome. These alterations include the adducts produced by many chemical carcinogens, but not the UV-induced cyclobutane pyrimidine dimer, which may be an exception. Recent studies in our laboratory have shown that the excision repair of pyrimidine dimers and certain other lesions is nonrandom in the mammalian genome, exhibiting a distinct preference for actively transcribed DNA sequences. An important consequence of this fact is that mutagenesis and carcinogenesis may be determined in part by the activities of the relevant genes. Repair may also be processive, and a model is proposed in which excision repair is coupled to transcription at the nuclear matrix. Similar but freely diffusing repair complexes may account for the lower overall repair efficiencies in the silent domains of the genome. Risk assessment in relation to chemical carcinogenesis requires assays that determine effective levels of DNA damage for producing malignancy. The existence of nonrandom repair in the genome casts into doubt the reliability of overall indicators of DNA binding and lesion repair for such determinations. Furthermore, some apparent differences between the intragenomic repair heterogeneity in rodent cells and that in human cells mandate a reevaluation of rodent test systems for human risk assessment. Tissue-specific and cell-specific differences in the coordinate regulation of gene expression and DNA repair may account for corresponding differences in the carcinogenic response.
Ruptured Congenital Aneurysms of the Sinuses of Valsalva
Authors: J. A. SZWEDA, E. H. DRAKE
Journal: Circulation (1962)

Two cases operated upon for ruptured sinus of Valsalva aneurysm are presented and discussed. Operations done previously for this condition are noted. Aspects of the deformity that are pertinent to its recognition and treatment are briefly reviewed.
Temporal representation in the control of movement
Authors: Daniel M. Corcos
Journal: Behavioral and Brain Sciences (1994)

Theories of the representation of specific kinetic and spatiotem-poral features of movement range from the explicit assertion that temporal aspects of movement are not represented (Kugler et al. 1980) to the idea that they are represented and that they have neurophysiological correlates (Ivry &amp; Corcos 1993; Ivry &amp; Keele 1989). Jeannerod's thesis is that mental and visual images have common mechanisms and that there is a link between the image to move and the mechanisms involved with movement. The target article takes the position that certain parameters are coded in motor representations (sect. 4) but that the duration of an action is not one of them. This position is based on the work of Gottlieb et al. (1989b) and of Decety et al. (1989). Both these studies are worth considering in detail. In Note 1, Jeannerod suggests that: “in time-constrained tasks subjects control the amplitude parameter of force impulses, whereas in spatially constrained tasks the duration of the force impulse is affected by accuracy demands.” This is not exactly correct. Excitation pulse intensity (amplitude) is modulated both in tasks that require spatial and those that require temporal accuracy. Excitation pulse duration is modulated for changes in movement distance and inertial load. If subjects are required to be very accurate spatially, they will move at less than maximum speed for a given distance and this is achieved by lower levels of excitation intensity (Gottlieb et al. 1990).
Abstract 3512: Expanded human regulatory iNKT cells exhibit direct cytotoxicity against hematolymphoid tumor targets
Authors: Wioleta Luszczek, Vanessa Morales-Tirado, Marie van der Merwe, Ko Kudo, Dario Campana, Asha Pillai
Journal: Cancer Research (2012)

Abstract CD1d-restricted invariant natural killer T (iNKT) cells are rare but potent innate regulatory cells capable of immune modulation via robust production of Th1/Th2 cytokines, as well as tumor immunosurveillance via direct cytotoxicity. Protocols to expand iNKT cells and augment their cytotoxicity would broaden their application in allogeneic transplantation and adjuvant anti-tumor immunotherapy. We have optimized a protocol for ex vivo expansion of highly purified human CD3+CD4negVα24+ iNKT cells from human peripheral blood mononuclear cells (PBMC). PBMCs were stimulated with an iNKT-specific glycolipid (α-GalCer), recombinant IL-2 and IL-7 and sorted to &amp;gt; 98% purity at day 7. Sorted iNKT cells were further expanded in the presence of irradiated allogeneic PBMCs, Vα24-specific TCR stimulation, and low-dose IL-2 and IL-7 for 21 days. This results in roughly 10^3-fold expansion, with peak yields of at day 21-28 of expansion (range 1.5 x 10^5 - 10.6 x 10^6 iNKT cells from 1 x 10^8 - 3.5 x 10^8 starting PBMC). At 28 days, these iNKT cells secrete high levels of IL-13, TNF-α, GM-CSF, and IL-4, moderate IL-2 and IFN-γ in anti-CD2/CD3/CD28 bead-stimulated Luminex supernatant assay. Day 28 expanded iNKT cells are dose-dependent suppressors of sorted autologous CD3+CD8+ effector T cells in 72-hr mixed leukocyte reaction (MLR). Anti-CD2/CD3/CD28 activation of these iNKT cells induced expression of high levels of key cytolytic effector molecules, including granzyme B. We therefore measured cytotoxicity of activated day 28 iNKT cells against various hematolymphoid tumor targets following co-incubation of iNKT cells versus control effector populations with firefly luciferase-transduced RS4:11 and Nalm6 (B-ALL), U937 (monocytic), and K562 (CML) targets. iNKT cell effectors (E) demonstrated dose-dependent cytotoxicity against B-lymphoid tumor targets (T) (e.g.: Nalm6: 37.7% at E:T 2:1, 17.7% at E:T 1:1, 7.7% at E:T 0.5:1), with no significant cytotoxicity against myeloid targets (e.g.: K562: 11.8% at E:T 2:1, 6.7 at E:T 1:1, 1.8 at E:T 0.5:1). Our results indicate that human iNKT cells expressing high levels of Th2 and regulatory cytokines can be potently expanded ex vivo and manifest cytotoxicity against B-ALL targets, supporting their potential application in tailored immunotherapy in the pre- and post-transplant setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3512. doi:1538-7445.AM2012-3512
Increased Risk of Type 2 Diabetes Despite Same Degree of Adiposity in Different Racial Groups
Authors: Kirsten A. McAuley, Sheila M. Williams, Jim I. Mann, Ailsa Goulding, Eleanor Murphy
Journal: Diabetes Care (2002)

As indigenous people of the South Pacific have rates of type 2 diabetes and obesity among the highest in the world (1,2), diabetes risk reduction strategies include identification of high-risk individuals. Different cutoffs to define overweight and obesity have been suggested for some indigenous people because they have more lean mass and less adipose tissue than Europeans with comparable BMIs (3). However, cutoffs for BMI should be based on risk of comorbidities associated with a given BMI, not simply with lean body mass. To further assist the process of defining appropriate BMI levels for South Pacific people, we have investigated insulin sensitivity in New Zealand women of Maori and European descent who have similar levels of BMI, fat, …
TCT-19 Fractional Flow Reserved Derived From Computed Tomographic Angiography (FFRCT) for Intermediate Severity Coronary Lesions: Results from the DeFACTO Trial (Determination of Fractional Flow Reserve by Anatomic Computed TOmographic Angiography)
Authors: James Min, Daniel Berman, Leslee Shaw, Laura Mauri, Bon-Kwon Koo, Andrejs Erglis, Jonathon Leipsic
Journal: Journal of the American College of Cardiology (2012)
Bleeding Times and Platelet Aggregation After Analgesics in Hemophilia
Authors: CAROL K. KASPER
Journal: Annals of Internal Medicine (1972)

The effect of aspirin, acetaminophen, propoxyphene, and placebo on the Ivy bleeding time, platelet aggregation, and platelet factor 3 availability was evaluated in a double-blind study of severe hemophilia. Acetaminophen and propoxyphene did not prolong the bleeding time and did not affect platelet function in vitro. These drugs can be used safely in severe hemophilia and probably also in other hemorrhagic disorders. Aspirin lengthened the bleeding time in all subjects, although the degree of prolongation varied in individual tests. Differences in the response of the bleeding time to aspirin could not be related to the results of in vitro platelet function tests. Apparently, bleeding times will have to be measured to determine whether a drug that interferes with platelet function in vitro will also interfere significantly with the formation of hemostatic plugs in vivo in the hemophilic patient.
Thermochemoradiotherapy Improves Oxygenation in Locally Advanced Breast Cancer
Authors: Ellen L. Jones, Leonard R. Prosnitz, Mark W. Dewhirst, P. Kelly Marcom, Patricia H. Hardenbergh, Lawrence B. Marks, David M. Brizel, Zeljko Vujaskovic
Journal: Clinical Cancer Research (2004)

The purpose of this research was to evaluate toxicity, response, and changes in oxygenation (pO(2)) in patients with locally advanced breast cancer (LABC) treated with concurrent taxol, hyperthermia (HT), and radiation therapy (RT) followed by mastectomy.Eighteen patients with LABC were enrolled from October 1995 through February 1999. Treatment consisted of taxol (175 mg/m(2)) given every 3 weeks for three cycles. Radiation therapy included the breast and regional nodes with a dose of 50 Gy, followed by a boost to 60-65 Gy for those not undergoing surgery. Mastectomy was performed for patients deemed resectable after this neoadjuvant program. HT was administered twice per week. Oxygenation was measured before the first HT treatment and 24 h after the first HT treatment.Fifteen of 18 patients responded, 6 with a clinical complete response, 9 with a partial clinical response, and 3 nonresponders. Thirteen underwent mastectomy with 3 pathological complete responses. Tumor hypoxia was present in 8 of 13 patients (pO(2) = 4.7 +/- 1.2 mmHg). Five patients had well-oxygenated tumors (pO(2) = 27.6 +/- 7.8 mmHg). Patients with well-oxygenated tumors before treatment as well as those with significant reoxygenation had a favorable clinical response. Tumor reoxygenation appeared to be temperature dependent and associated with the lower thermal doses.This novel therapeutic program resulted in a high response rate in patients with LABC. Hyperthermia may offer a strategy for improving tumor reoxygenation with consequent treatment response. However, the effect of hyperthermia on tumor reoxygenation appears to depend on thermal dose and requires additional investigation.
Positioning of nasogastric tubes.
Authors: E N Fry
Journal: BMJ (1978)

perimentally it is well established that once the endothelial barrier is breeched the stage is set for atherosclerosis and even a mild rise in plasma cholesterol concentration above 5 5 mmol/l (220 mg/100 ml) is sufficient to induce atherosclerotic change.However, changes may develop before there is any detectable rise in blood lipids.4It is hardly to be expected that dietary cholesterol as calculated from tables and on a single occasion would be representative of the usual amount consumed from day to day and over the many years of developing athero- sclerosis.However, it is known that dietary cholesterol contributes about one-quarter to one-third to plasma cholesterol,> which is a very substantial amount since the body synthesises all its requirements.Plasma concentrations are also greatly influenced by the amount and composition of fat in the diet.Professor Yudkin makes no reference to these important aspects, an appreciation of which puts the situation into better prospective.
Hermodulins: bispecific ligand traps inhibit breast tumor growth and metastasis.
Authors: L Turin, M Beryt, J Zhang, C Brdlik, P Jin, J Huang, X Bai, H Shepard
Journal: Cancer Research (2009)

Abstract Abstract #4127 Signalling by the human EGF (HER) receptor family can induce tumorigenicity and metastasis of cancer cells. Activation of these receptors has been associated with aggressive phenotypes and poor prognosis of breast cancer and other malignancies. Currently approved HER family targeted therapeutics are primarily directed against one member of the HER family.&amp;#x2028; We have engineered a family of bispecific (HER1:HER3) heterodimers comprised of a human IgG1-Fc fragment fused with modified extracellular domains of HER1 and HER3. These compounds, termed Hermodulins, act as “ligand traps” and inhibit ligand-stimulated activity of all members of the HER family. In this study we have shown that Hermodulins can inhibit in vitro growth and motility in breast cancer cell lines, act synergistically with other HER-directed tyrosine kinase inhibitors and monoclonal antibody therapeutics in tumor cell antiproliferation assays, and decrease the formation of osteolytic bone metastases in animal models. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4127.
IMMUNOCHEMICAL STUDIES ON MOUSE MYELOMA PROTEINS REACTIVE WITH DEXTRANS OR WITH FRUCTOSANS AND ON HUMAN ANTILEVANS
Authors: John Cisar, Elvin A. Kabat, Jerry Liao, Michael Potter
Journal: The Journal of Experimental Medicine (1974)

Four BALB/c IgA mouse myeloma proteins (W3129, W3434, QUPC 52, and UPC 102) reactive with dextran, four myeloma proteins reactive with fructosans, three IgA (W3082, UPC 61, and Y5476), and one IgG2a (UPC 10), and two human antilevans were studied immunochemically. Quantitative precipitin and inhibition assays showed that W3129, W3434, and QUPC 52 had specificities for isomaltose oligosaccharides similar to those previously found with alpha(1 --> 6)-specific human antidextrans. W3129 and W3434 were most complementary to IM5 but W3129 reacted equally with IM4 and IM3 while W3434 had a greater affinity for IM4 than IM3. QUPC 52 had a larger combining region and was most complementary to IM6. Protein UPC 102 (IgA), like MOPC 104E (IgM) (27), was most complementary to the alpha(1 --> 3)-linked trisaccharide, nigerotriose, and thus differed from J558 (29), which was inhibited best by nigeropentaose. UPC 102 was similar to J558 but they differed from MOPC 104E in their reactions with non-alpha(1 --> 3)-linked disaccharides. The fructosan-specific myeloma proteins fell into two groups with different specificities. The first group, W3082 (IgA), UPC 61 (IgA), and the previously studied J606 (IgG3) (28, 29), reacted with inulin and W3082 and UPC 61 appeared to have identical specificities for beta(2 --> 1)-linked fructofuranosyl residues with maximum complementarity for the tetrasaccharide betaDfructofuranosyl (2 --> 1)betaDfructofuranosyl(2 --> 1)betaDfructofuranosyl(2 --> 6)Dglucose while protein J606 was inhibited best by the trisaccharide betaDfructofuranosyl(2 --> 1)betaDfructofuranosyl(2 --> 6)Dglucose. W3082 and UPC 61 also differed from J606 in their behavior toward sucrose and betaDfructofuranosyl(2 --> 6)Dglucose as compared with alphaDglucosyl(1 --> 3)Dfructose (turanose). The second group containing myeloma proteins UPC 10 (IgG2a) and Y5476 (IgA) behaved similarly to human antilevans in that neither reacted with inulin nor were they inhibited by the beta(2 --> 1)-linked fructose oligosaccharides. Unlike the beta(2 --> 1)-specific proteins, they reacted with perennial rye grass levan that contained over 90% beta(2 --> 6)links. The differences in specificity and site size among homogeneous mouse myeloma proteins reactive with the same antigenic determinant are completely consistent with the concept that they represent products of homogeneous clones selected from the known heterogeneous population of antibody-forming cells.
Ovalbumin aerosol challenge in actively sensitized guinea pigs: relationship between airway microvascular leakage and airflow obstruction
Authors: K. P. Hui, J. Lötvall, D. F. Rogers, P. J. Barnes, F. K. Chung
Journal: Allergy (1992)

Airway inflammation is a common feature of asthma, and one of the cardinal features of inflammation is increased microvascular permeability. We investigated the characteristics of inhaled ovalbumin challenge‐induced airflow obstruction and airway microvascular leakage in vivo in mechanically ventilated guinea pigs actively sensitized to ovalbumin. A method was used to quantify both airflow obstruction and airway microvascular leakage in order to investigate the relationship between these 2 pathophysiological features in the same animal. Airway microvascular leakage was assessed by Evans blue dye extravasation into airway tissues. Actively sensitized guinea pigs developed both acute airflow obstruction (increased lung resistance and reduced dynamic lung compliance) and Evans blue dye extravasation in response to exposure to aerosolised ovalbumin. Evans blue dye extravasation was preferentially distributed in the distal airways and correlated with airflow obstruction. The results show that inhaled allergen induced both acute airflow obstruction and airway microvascular leakage.
C-MYC–induced Apoptosis in Polycystic Kidney Disease Is Bcl-2 and p53 Independent
Authors: Marie Trudel, Jacqueline Lanoix, Laura Barisoni, Marie-José Blouin, Marc Desforges, Catherine L'Italien, Vivette D'Agati
Journal: The Journal of Experimental Medicine (1997)

The SBM mouse is a unique transgenic model of polycystic kidney disease (PKD) induced by the dysregulated expression of c-myc in renal tissue. In situ hybridization analysis demonstrated intense signal for the c-myc transgene overlying tubular cystic epithelium in SBM mice. Renal proliferation index in SBM kidneys was 10-fold increased over nontransgenic controls correlating with the presence of epithelial hyperplasia. The specificity of c-myc for the proliferative potential of epithelial cells was demonstrated by substitution of c-myc with the proto-oncogene c-fos or the transforming growth factor (TGF)-α within the same construct. No renal abnormalities were detected in 13 transgenic lines established, indicating that the PKD phenotype is dependent on functions specific to c-myc. We also investigated another well characterized function of c-myc, the regulation of apoptosis through pathways involving p53 and members of the bcl-2 family, which induce and inhibit apoptosis, respectively. The SBM kidney tissues, which overexpress c-myc, displayed a markedly elevated (10–100-fold) apoptotic index. However, no significant difference in bcl-2, bax, or p53 expression was observed in SBM kidney compared with controls. Direct proof that the heightened renal cellular apoptosis in PKD is not occurring through p53 was obtained by successive matings between SBM and p53−/− mice. All SBM offspring, irrespective of their p53 genotype, developed PKD with increased renal epithelial apoptotic index. In addition, overexpression of both bcl-2 and c-myc in double transgenic mice (SBB+/SBM+) also produced a similar PKD phenotype with a high apoptotic rate, showing that c-myc can bypass bcl-2 in vivo. Thus, the in vivo c-myc apoptotic pathway in SBM mice occurs through a p53- and bcl-2–independent mechanism. We conclude that the pathogenesis of PKD is c-myc specific and involves a critical imbalance between the opposing processes of cell proliferation and apoptosis.
Meningitis Caused by Gram-Negative Bacilli
Authors: STEVEN L. BERK
Journal: Annals of Internal Medicine (1980)

Thirty adults with meningitis caused by gram-negative bacilli were observed from 1968 to 1978 at four hospitals associated with Boston University School of Medicine. Equal numbers of two distinct types of gram-negative bacillary meningitis—spontaneously occurring meningitis and meningitis after neurosurgery—were found. Spontaneously occurring meningitis appeared to have an abrupt onset, a relatively fulminant course, and to be caused most often by Escherichia coli and Haemophilus influenzae. Meningitis occurring after neurosurgical procedures was more insidious in onset, more protracted in course, and more often caused by organisms resistant to multiple antibiotics. Approaches to therapy are based on the differences in character of these two types of meningitis.