tbuckley/cabot-search huggingface dataset:
Changes in pulmonary function tests following antibiotics in infants with pulmonary exacerbation of cystic fibrosis
Authors: Shahid Sheikh, Rob Flucke, Nancy Ryan-Wenger, Karen McCoy
Journal: European Respiratory Journal (2013)

Progressive lung disease plays an important role in CF morbidity. In older patients, improvement in PFT during CF exacerbation reflect clinical improvement but similar effectiveness of PFT in infants is not well known.  Methods: After local IRB approval, charts of all patients with CF who underwent infant PFT (under sedation with raised volume thoraco-abdominal technique) before and after 2 weeks of I/V antibiotic therapy for CF exacerbation between 2000-2012 at Nationwide Children9s Hospital, Columbus, OH, were reviewed and included in this study.  Results: Forty-one studies were completed in 28 patients, mean age 20.8 ±48 weeks. IV antibiotic therapy was received in the home by 15 (56%) and in the hospital by 13 (43%) patients. Length of hospital stay averaged 7.7 ±6.8 days. The mean number of antibiotic days was 17.8 ±4.9.  Thirty-one of 41 (75.6%) studies showed significant improvement. There was no improvement in one and remaining 9 studies were within normal limits at baseline. There were no significant differences in PFT changes between patients who received IV antibiotics at home or in the hospital, or whether or not pseudomonas or MRSA were present in throat cultures.  Conclusions: Among infants with CF-related pulmonary exacerbations, there was significant improvement in PFT in most of the infants after IV antibiotic therapy.
Nonenzymatic glycosylation in vitro and in bovine endothelial cells alters basic fibroblast growth factor activity. A model for intracellular glycosylation in diabetes.
Authors: I Giardino, D Edelstein, M Brownlee
Journal: Journal of Clinical Investigation (1994)

Intracellular sugars are more reactive glycosylating agents than glucose.In vitro nonenzymatic glycosylation of basic fibroblast growth factor (bFGF) by fructose, glucose-6-phos- phate (G6P), or glyceraldehyde-3-phosphate (G3P) reduced high affinity heparin-binding activity of recombinant bFGF by 73, 77, and 89%, respectively.Mitogenic activity was reduced 40, 50, and 90%.To investigate the effects of bFGF glycosylation in GM7373 endothelial cells, we first demon- strated that GLUT-1 transporters were not downregulated by increased glucose concentration.In 30 mM glucose, the rate of glucose transport increased 11.6-fold, and the intra- cellular glucose concentration increased sixfold at 24 h and fivefold at 168 h.The level of total cytosolic protein modified by advanced glycosylation endproducts (AGEs) was in- creased 13.8-fold at 168 h.Under these conditions, mitogenic activity of endothelial cell cytosol was reduced 70%.Anti- bFGF antibody completely neutralized the mitogenic activ- ity at both 5 and 30 mM glucose, demonstrating that all the mitogenic activity was due to bFGF.Immunoblotting and ELISA showed that 30 mM glucose did not decrease detectable bFGF protein, suggesting that the marked decrease in bFGF mitogenic activity resulted from posttranslational modification of bFGF induced by elevated glucose concen- tration.Cytosolic AGE-bFGF was increased 6.1-fold at 168 h.These data are consistent with the hypothesis that nonen- zymatic glycosylation of intracellular protein alters vascular cell function.(J.Clin.Invest.94:110-117.)Key words: glu- cose * advanced
Reversal of Tumor-induced Dendritic Cell Paralysis by CpG Immunostimulatory Oligonucleotide and Anti–Interleukin 10 Receptor Antibody
Authors: Alain P. Vicari, Claudia Chiodoni, Céline Vaure, Smina Aït-Yahia, Christophe Dercamp, Fabien Matsos, Olivier Reynard, Catherine Taverne, Philippe Merle, Mario P. Colombo, Anne O'Garra, Giorgio Trinchieri, Christophe Caux
Journal: The Journal of Experimental Medicine (2002)

Progressing tumors in man and mouse are often infiltrated by dendritic cells (DCs). Deficient antitumor immunity could be related to a lack of tumor-associated antigen (TAA) presentation by tumor-infiltrating DCs (TIDCs) or to a functional defect of TIDCs. Here we investigated the phenotype and function of TIDCs in transplantable and transgenic mouse tumor models. Although TIDCs could encompass various known DC subsets, most had an immature phenotype. We observed that TIDCs were able to present TAA in the context of major histocompatibility complex class I but that they were refractory to stimulation with the combination of lipopolysaccharide, interferon γ, and anti-CD40 antibody. We could revert TIDC paralysis, however, by in vitro or in vivo stimulation with the combination of a CpG immunostimulatory sequence and an anti-interleukin 10 receptor (IL-10R) antibody. CpG or anti–IL-10R alone were inactive in TIDCs, whereas CpG triggered activation in normal DCs. In particular, CpG plus anti–IL-10R enhanced the TAA-specific immune response and triggered de novo IL-12 production. Subsequently, CpG plus anti–IL-10R treatment showed robust antitumor therapeutic activity exceeding by far that of CpG alone, and elicited antitumor immune memory.
Aberrant Overexpression of the Wilms Tumor Gene (WT1) in Human Leukemia
Authors: Kazushi Inoue, Hiroyasu Ogawa, Yoshiaki Sonoda, Takafumi Kimura, Hideaki Sakabe, Yoshihiro Oka, Seigou Miyake, Hiroya Tamaki, Yusuke Oji, Tamotsu Yamagami, Toyoshi Tatekawa, Toshihiro Soma, Tadamitsu Kishimoto, Haruo Sugiyama
Journal: Blood (1997)
Effect of Prior Intensive Insulin Treatment During the Diabetes Control and Complications Trial (DCCT) on Peripheral Neuropathy in Type 1 Diabetes During the Epidemiology of Diabetes Interventions and Complications (EDIC) Study
Authors: James W. Albers, William H. Herman, Rodica Pop-Busui, Eva L. Feldman, Catherine L. Martin, Patricia A. Cleary, Barbara H. Waberski, John M. Lachin
Journal: Diabetes Care (2010)

To evaluate the impact of former intensive versus conventional insulin treatment on neuropathy in Diabetes Control and Complications Trial (DCCT) intensive and conventional treatment subjects with type 1 diabetes 13-14 years after DCCT closeout, during which time the two groups had achieved similar A1C levels.Clinical and nerve conduction studies (NCSs) performed during the DCCT were repeated during the Epidemiology of Diabetes Interventions and Complications (EDIC) study by examiners masked to treatment status on 603 former intensive and 583 former conventional treatment subjects. Clinical neuropathy was defined by symptoms, sensory signs, or reflex changes consistent with distal polyneuropathy and confirmed with NCS abnormalities involving two or more nerves among the median, peroneal, and sural nerves.The prevalence of neuropathy increased 13-14 years after DCCT closeout from 9 to 25% in former intensive and from 17 to 35% in former conventional treatment groups, but the difference between groups remained significant (P < 0.001), and the incidence of neuropathy remained lower among former intensive (22%) than former conventional (28%) treatment subjects (P = 0.0125). Analytic models of incident neuropathy that adjusted for differences in NCS results at DCCT closeout showed no significant risk reduction associated with former intensive treatment during follow-up (odds ratio 1.17 [95% CI 0.84-1.63]). However, a significant persistent treatment group effect was observed for several NCS measures. Longitudinal analyses of overall glycemic control showed a significant association between mean A1C and measures of incident and prevalent neuropathy.The benefits of former intensive insulin treatment persisted for 13-14 years after DCCT closeout and provide evidence of a durable effect of prior intensive treatment on neuropathy.
The Use of Metformin and the Incidence of Lung Cancer in Patients With Type 2 Diabetes
Authors: Brielan B. Smiechowski, Laurent Azoulay, Hui Yin, Michael N. Pollak, Samy Suissa
Journal: Diabetes Care (2012)

Observational studies have associated metformin use with a decreased risk of lung cancer incidence in patients with type 2 diabetes, but the studies had important methodological shortcomings. The objective of this study was to determine whether metformin use is associated with a decreased risk of lung cancer in patients with type 2 diabetes, while avoiding previous biases.Using the U.K. General Practice Research Database, we assembled a cohort of patients newly treated with oral hypoglycemic agents (OHAs) between 1988 and 2009. A nested case-control analysis was conducted, where case subjects with lung cancer occurring during follow-up were matched with up to 10 control subjects for age, sex, calendar time, and duration of follow-up. Conditional logistic regression was used to estimate adjusted rate ratios of lung cancer associated with ever use of metformin, along with measures of duration and cumulative dose. Models were adjusted for potential confounders, which included smoking.The cohort included 115,923 new users of OHAs, with 1,061 patients diagnosed with lung cancer during follow-up (rate 2.0/1,000 person-years). Metformin use was not associated with a decreased rate of lung cancer (rate ratio 0.94 [95% CI 0.76-1.17]). No dose-response was observed by number of prescriptions received, cumulative duration of use, and dose.Metformin use is not associated with a decreased risk of lung cancer in patients with type 2 diabetes. The decreased risk reported in other observational studies is likely due to bias from methodological shortcomings. Nonetheless, greater consideration should be given to clarify inconsistencies between experimental models and population studies.
Patient Personality and Therapist Response: An Empirical Investigation
Authors: Antonello Colli, Annalisa Tanzilli, Giancarlo Dimaggio, Vittorio Lingiardi
Journal: American Journal of Psychiatry (2013)

The aim of this study was to examine the relationship between therapists' emotional responses and patients' personality disorders and level of psychological functioning.A random national sample of psychiatrists and clinical psychologists (N=203) completed the Therapist Response Questionnaire to identify patterns of therapists' emotional response, and the Shedler-Westen Assessment Procedure-200 to assess personality disorders and level of psychological functioning in a randomly selected patient currently in their care and with whom they had worked for a minimum of eight sessions and a maximum of 6 months (one session per week).There were several significant relationships between therapists' responses and patients' personality pathology. Paranoid and antisocial personality disorders were associated with criticized/mistreated countertransference, and borderline personality disorder was related to helpless/inadequate, overwhelmed/disorganized, and special/overinvolved countertransference. Disengaged countertransference was associated with schizotypal and narcissistic personality disorders and negatively associated with dependent and histrionic personality disorders. Schizoid personality disorder was associated with helpless/inadequate responses. Positive countertransference was associated with avoidant personality disorder, which was also related to both parental/protective and special/overinvolved therapist responses. Obsessive-compulsive personality disorder was negatively associated with special/overinvolved therapist responses. In general, therapists' responses were characterized by stronger negative feelings when working with lower-functioning patients.Patients' specific personality pathologies are associated with consistent emotional responses, which suggests that clinicians can make diagnostic and therapeutic use of their responses to patients.
Activation of Mitochondrial ATP-Sensitive K <sup>+</sup> Channel for Cardiac Protection Against Ischemic Injury Is Dependent on Protein Kinase C Activity
Authors: Yigang Wang, Kyoji Hirai, Muhammad Ashraf
Journal: Circulation Research (1999)

Abstract —Protein kinase C (PKC) is involved in the second messenger signaling cascade during ischemic and Ca 2+ preconditioning. Given that the pharmacological activation of mitochondrial ATP-sensitive K + (mitoK ATP ) channels also mimics preconditioning, the mechanisms linking PKC activation and mitoK ATP channels remain to be established. We hypothesize that PKC activity is important for the opening of the mitoK ATP channel. To examine this, a specific opener of the mitoK ATP channel, diazoxide, was used in conjunction with subcellular distribution of PKC in a model of ischemia/reperfusion (I/R). Langendorff-perfused rat hearts were subjected to 40-minute ischemia followed by 30-minute reperfusion. Effects of activation of the mitoK ATP channel and other interventions on functional, biochemical, and pathological changes in ischemic hearts were assessed. In hearts treated with diazoxide, left ventricular end-diastolic pressure and coronary flow were significantly improved after I/R; lactate dehydrogenase release was also significantly decreased. The morphology was well preserved in diazoxide-treated hearts compared with nontreated ischemic control hearts. The salutary effects of diazoxide on the ischemic injury were similar to those of Ca 2+ preconditioning. Administration of sodium 5-hydroxydecanoate, an effective blocker of the mitoK ATP channel, or chelerythrine or calphostin C, an inhibitor of PKC, during diazoxide pretreatment or during continuous presence of diazoxide in the ischemic period, completely abolished the beneficial effects of the diazoxide on the I/R injury. Blockade of Ca 2+ entry during diazoxide treatment by inhibiting the L-type Ca 2+ channel with verapamil also completely reversed the beneficial effect of diazoxide during I/R. PKC-α was translocated to sarcolemma, whereas PKC-δ was translocated to the mitochondria and intercalated disc, and PKC-ε was translocated to the intercalated disc of the diazoxide-pretreated hearts. Colocalization studies for mitochondrial distribution with tetramethylrhodamine ethyl ester (TMRE) and PKC isoforms by immunoconfocal microscopy revealed that PKC-δ antibody specifically stained the mitochondria. ATP was significantly increased in the diazoxide-treated hearts. Moreover, the data suggest that activation and translocation of PKC to mitochondria appear to be important for the protection mediated by mitoK ATP channel.
Selection of Antigen-specific T Cells by a Single IEk Peptide Combination
Authors: Chih-Pin Liu, David Parker, John Kappler, Philippa Marrack
Journal: The Journal of Experimental Medicine (1997)

In normal mice, major histocompatibility complex (MHC) proteins are bound to many different peptides, derived from the proteins of their host. In the thymus, the diversity of this collection of MHC + peptide ligands allows thymocytes bearing many different T cell receptors (TCRs) to mature by low avidity reactions between the MHC + peptide ligands and the thymocyte TCRs. To investigate this problem, the selection of T cells specific for a well-studied combination of MHC + peptide, IEk + moth cytochrome c 88–103 (MCC), was investigated. Mice were created that expressed IEk bound to a single peptide, either a variant of MCC in which a critical TCR contact residue, 99K, was changed to A, or a variant of a mouse hemoglobin 64–76 (Hb) peptide, 72A. IEk bound to the MCC variant caused the clonal deletion of some T cells specific for the IEk + MCC ligand; nevertheless, it also positively selected many T cells that could react with this ligand. Some of the TCRs on the selected T cells were related to those on cells from normal mice and some were not. IEk bound to the Hb variant, on the other hand, did not select any T cells which could react with IEk + MCC. These results demonstrate that although positive selection is a partially degenerate event, the sequence of the peptide involved in positive selection controls the selected repertoire.
Cardiovascular evaluation, including resting and exercise electrocardiography, before participation in competitive sports: cross sectional study
Authors: F. Sofi, A. Capalbo, N. Pucci, J. Giuliattini, F. Condino, F. Alessandri, R. Abbate, G. F. Gensini, S. Califano
Journal: BMJ (2008)

<b>Objective</b> To evaluate the clinical usefulness of complete preparticipation cardiovascular screening in a large cohort of sports participants. <b>Design</b> Cross sectional study of data over a five year period. <b>Setting</b> Institute of Sports Medicine in Florence, Italy. <b>Participants</b> 30 065 (23 570 men) people seeking to obtain clinical eligibility for competitive sports. <b>Main outcome measures</b> Results of resting and exercise 12 lead electrocardiography. <b>Results</b> Resting 12 lead ECG patterns showed abnormalities in 1812 (6%) participants, with the most common abnormalities (&gt;80%) concerning innocent ECG changes. Exercise ECG showed an abnormal pattern in 1459 (4.9%) participants. Exercise ECG showed cardiac anomalies in 1227 athletes with normal findings on resting ECG. At the end of screening, 196 (0.6%) participants were considered ineligible for competitive sports. Among the 159 participants who were disqualified at the end of the screening for cardiac reasons, a consistent proportion (n=126, 79.2%) had shown innocent or negative findings on resting 12 lead ECG but clear pathological alterations during the exercise test. After adjustment for possible confounders, logistic regression analysis showed that age &gt;30 years was significantly associated with an increased risk of being disqualified for cardiac findings during exercise testing. <b>Conclusions</b> Among people seeking to take part in competitive sports, exercise ECG can identify those with cardiac abnormalities. Follow-up studies would show if disqualification of such people would reduce the incidence of CV events among athletes.
Restoration of hypothalamic lipid sensing normalizes energy and glucose homeostasis in overfed rats
Authors: A. Pocai
Journal: Journal of Clinical Investigation (2006)

Short-term overfeeding blunts the central effects of fatty acids on food intake and glucose production. This acquired defect in nutrient sensing could contribute to the rapid onset of hyperphagia and insulin resistance in this model. Here we examined whether central inhibition of lipid oxidation is sufficient to restore the hypothalamic levels of long-chain fatty acyl-CoAs (LCFA-CoAs) and to normalize food intake and glucose homeostasis in overfed rats. To this end, we targeted the liver isoform of carnitine palmitoyltransferase-1 (encoded by the CPT1A gene) by infusing either a sequence-specific ribozyme against CPT1A or an isoform-selective inhibitor of CPT1A activity in the third cerebral ventricle or in the mediobasal hypothalamus (MBH). Inhibition of CPT1A activity normalized the hypothalamic levels of LCFA-CoAs and markedly inhibited feeding behavior and hepatic glucose fluxes in overfed rats. Thus central inhibition of lipid oxidation is sufficient to restore hypothalamic lipid sensing as well as glucose and energy homeostasis in this model and may be an effective approach to the treatment of diet-induced obesity and insulin resistance.
Inhibition of H-Y cell-mediated cytolysis by H-2Db antiserum.
Authors: G C Koo, C L Goldberg, F W Shen
Journal: The Journal of Experimental Medicine (1979)

Assays of H-Y-specific cell-mediated cytolysis (CMC) in vitro were carried out with B6 female effector cells and B6 male target cells. This lytic system depends on compatibility for H-2Db but not for H-2Kb. Antibody to H-2Db but not to H-2Kb blocked the CMC assay. However, maximal blocking required exposure to the target cells to H-2Db antibody for up to 2 h. This interval is far longer than would be required for blocking of a pre-existing H-Y:H-2Db complex, and seems more consonant with a membrane reorganization bringing H-Y and H-2Db together, as proposed from mapping studies. The question whether the postulated configurational change affecting H-Y and H-2Db is a necessary feature of CMC awaits further study.
Short-Term Thalidomide Incorporated Into Double Autologous Stem-Cell Transplantation Improves Outcomes in Comparison With Double Autotransplantation for Multiple Myeloma
Authors: Michele Cavo, Francesco Di Raimondo, Elena Zamagni, Francesca Patriarca, Paola Tacchetti, Antonio Francesco Casulli, Silvestro Volpe, Giulia Perrone, Antonio Ledda, Michela Ceccolini, Catello Califano, Catia Bigazzi, Massimo Offidani, Piero Stefani, Filippo Ballerini, Mauro Fiacchini, Antonio de Vivo, Annamaria Brioli, Patrizia Tosi, Michele Baccarani
Journal: Journal of Clinical Oncology (2009)

To assess potential benefits with thalidomide incorporated into double autologous stem-cell transplantation (ASCT) for younger patients with newly diagnosed multiple myeloma (MM).One hundred thirty-five patients who received thalidomide from induction until the second ASCT were retrospectively analyzed in comparison with an equal number of pair mates treated with double ASCT not including thalidomide.On an intention-to-treat basis, the addition of thalidomide to double ASCT effected a significant improvement in the rate (68% v 49%; P = .001) and duration (62% v 33% at 4 years; P < .001) of at least very good partial response (VGPR), time to progression (TTP; 61% v 41% at 4 years; P < .001) and progression-free survival (PFS; 51% v 31% at 4 years; P = .001). A trend was also noted for extended overall survival (OS) among thalidomide-treated patients (69% at 5 years v 53% for the control group), although the difference between the two groups was not statistically significant (P = .07). Benefits with thalidomide in increasing the rate of VGPR or better response, TTP, and PFS were confirmed in a multivariate analysis. Median OS after relapse was 24 months for patients receiving thalidomide added to double ASCT and 25 months for the control group. Overall, 17% of patients discontinued thalidomide, including 8% because of drug-related adverse events.In comparison with double ASCT, the addition of first-line thalidomide to double ASCT improved clinical outcomes. Short-term thalidomide was generally well tolerated and had no adverse impact on postrelapse survival.
Increased Glycemic Variability Is Independently Associated With Length of Stay and Mortality in Noncritically Ill Hospitalized Patients
Authors: Carlos E. Mendez, Ki-Tae Mok, Ashar Ata, Robert J. Tanenberg, Jorge Calles-Escandon, Guillermo E. Umpierrez
Journal: Diabetes Care (2013)

To investigate the association between glycemic variability (GV) and both length of stay (LOS) and 90-day mortality in noncritically ill hospitalized patients.This study retrospectively analyzed 4,262 admissions to the general medicine or surgery services during a 2 year period. Patients with point-of-care glucose monitoring and a minimum of two glucose values per day on average were selected. GV was assessed by SD and coefficient of variation (CV). Data were analyzed with linear and logistic multivariate regression analysis in separate models for SD and CV. Analysis was performed with generalized estimating equations to adjust for correlation between multiple admissions in some individual cases.After exclusions, 935 admissions comprised the sample. Results of adjusted analysis indicate that for every 10 mg/dL increase in SD and 10-percentage point increase in CV, LOS increased by 4.4 and 9.7%, respectively. Relative risk of death in 90 days also increased by 8% for every 10-mg/dL increase in SD. These associations were independent of age, race, service of care (medicine or surgery), previous diagnosis of diabetes, HbA1c, BMI, the use of regular insulin as a sole regimen, mean glucose, and hypoglycemia occurrence during the hospitalization.Our results indicate that increased GV during hospitalization is independently associated with longer LOS and increased mortality in noncritically ill patients. Prospective studies with continuous glucose monitoring are necessary to investigate this association thoroughly and to generate therapeutic strategies targeted at decreasing GV.