tbuckley/cabot-search huggingface dataset:
Continuous Positive Airway Pressure Treatment Rapidly Improves Insulin Sensitivity in Patients with Obstructive Sleep Apnea Syndrome
Authors: Igor A. Harsch, Simin Pour Schahin, Martin Radespiel-Tröger, Oliver Weintz, Holger Jahreiß, Florian S. Fuchs, Gunther H. Wiest, Eckhart G. Hahn, Tobias Lohmann, Peter C. Konturek, Joachim H. Ficker
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The obstructive sleep apnea syndrome is typically associated with conditions known to increase insulin resistance as hypertension, obesity, and diabetes. We investigated whether obstructive sleep apnea itself is an independent risk factor for increased insulin resistance and whether continuous positive airway pressure (CPAP) treatment improves insulin sensitivity. Forty patients (apnea-hypopnea index > 20) were treated with CPAP. Before, 2 days after, and after 3 months of effective CPAP treatment, hyperinsulinemic euglycemic clamp studies were performed. Insulin sensitivity significantly increased after 2 days (5.75 +/- 4.20 baseline versus 6.79 +/- 4.91 micromol/kg.min; p = 0.003) and remained stable after 3 months of treatment. The improvement in insulin sensitivity after 2 days was much greater in patients with a body mass index less than 30 kg/m2 than in more obese patients. The improved insulin sensitivity after 2 nights of treatment may reflect a decreasing sympathetic activity, indicating that sleep apnea is an independent risk factor for increased insulin resistance. The effect of CPAP on insulin sensitivity is smaller in obese patients than in nonobese patients, suggesting that in obese individuals insulin sensitivity is mainly determined by obesity and, to a smaller extent, by sleep apnea.
Normal values for respiratory resistance using forced oscillation in subjects &gt;65 years old
Authors: Y. F. Guo
Journal: European Respiratory Journal (2005)

The aim of the present study was to determine reference values and predictive variables for respiratory impedance (Zrs) by the forced oscillation technique (FOT) in subjects aged>65 yrs. The investigation involved a prospective study of nonsmoking subjects, with normal forced expiratory volumes. The Zrs parameters, which included average resistance between 4-16 Hz (R4-16), average resistance between 4-30 Hz (RM), resonant frequency (FN), capacitance (C) and inertance (I), were measured along with forced expiratory manoeuvres. Every subject had each parameter measured in the same sequence using FOT and spirometry. A total of 223 subjects aged 83+/-8 yrs were included in the study. The mean values for forced expiratory volume in one second (FEV1) % predicted were 110+/-23. The forced vital capacity (FVC) % pred was 114+/-21 and the FEV1/FVC % pred was 112+/-11. The mean values for the Zrs parameters were: R4-16: 0.25+/-0.07 kPa.s-1.L-1; RM: 0.25+/-0.06 kPa.s-1.L-1; FN: 11.0+/-2.8 Hz; I: 1.17+/-0.26 Pa.L-1.s-2; and C: 20.5+/-9.0 mL.hPa-1. In multiple regression models adjusted for age, sex, height and weight, height was the most influential predictor for Zrs parameters based on the magnitude of the regression coefficient. In conclusion, it was found that height was the best predictor for respiratory impedance parameters. Contribution of age and weight was negligible. However, the level of predictability for respiratory impedance parameters by regression equations was low.
EXCESSIVE INFANT CRYING (COLIC) IN RELATION TO PARENT BEHAVIOR
Authors: ANN H. STEWART, I. H. WEILAND, ALLAN R. LEIDER, CHARLES A. MANGHAM, THOMAS H. HOLMES, HERBERT S. RIPLEY
Journal: American Journal of Psychiatry (1954)

1. The interaction between parents and infants and its relationship to crying was studied in 18 infants from 13 families. 2. Crying was found to be a response to tension which arose internally from unsatisfied needs or from inappropriate external stimulation. 3. The quantity of this tension was affected by the parent's behavior as it related to the satisfaction of the infant's needs. 4. This behavior was perceived by the infant through the sensory and proprioceptive systems. 5. The parents of babies who cried excessively responded inappropriately and inconsistently to their infant' needs with over-stimulation or with relative neglect. 6. The infants who cried excessively did not develop security in interpersonal relationships to the same extent as those who cried very little. 7. In addition to excessive crying these infants demonstrated deviations such as: regurgitation, night-waking, growth failure, nasal hyperfunction, increased muscle tension, variability in gastrointestinal functions and absolute eosinophil counts. They also had frequent illnesses.
Altered Patterns of Gene Expression in Response to Myocardial Infarction
Authors: Lawrence W. Stanton, Lisa J. Garrard, Deborah Damm, Brett L. Garrick, Andrew Lam, Ann M. Kapoun, Qiang Zheng, Andrew A. Protter, George F. Schreiner, R. Tyler White
Journal: Circulation Research (2000)

The use of cDNA microarrays has made it possible to simultaneously analyze gene expression for thousands of genes. Microarray technology was used to evaluate the expression of >4000 genes in a rat model of myocardial infarction. More than 200 genes were identified that showed differential expression in response to myocardial infarction. Gene expression changes were monitored from 2 to 16 weeks after infarction in 2 regions of the heart, the left ventricle free wall and interventricular septum. A novel clustering program was used to identify patterns of expression within this large set of data. Unique patterns were revealed within the transcriptional responses that illuminate changes in biological processes associated with myocardial infarction.
Effects of oral calcium gluconate on gastric acid secretion and serum gastrin concentration in man.
Authors: M J Brodie, P C Ganguli, A Fine, T J Thomson
Journal: Gut (1977)

A single oral dose of 4A46 mmol calcium gluconate at pH 5-6 was administered intra- gastrically to 15 male volunteers without gastrointestinal disease.There was a significant rise in acid output from 30-90 minutes after the calcium was given compared with the basal hourly collec- tion.The serum gastrin level 30 minutes after calcium administration was significantly raised, but no correlation could be demonstrated between the acid and gastrin responses.Serum calcium levels were unchanged throughout.An equimolar dose of magnesium sulphate had no such effects.This study suggests that the intragastric administration of calcium results in independent release of gastric acid and gastrin from the gastric mucosa.Intravenous infusion of calcium chloride has been shown to stimulate gastric acid secretion (Barreras, 1970) and a gastrin response (Reeder et al., 1970;Passaro et al., 1972;Reeder et al., 1974).Although these effects are reproduced by orally administered calcium carbonate, the acid secretory response to this alkaline substance is more pronounced than that of the other alkalis which do not contain calcium (Breuhaus et al., 1950; Fordtran, 1968; Barreras, 1973; Levant et al., 1973).Recently, some workers have shown that the intragastric infusion of calcium chloride, even at an acid pH, stimulated gastric acid secretion (Holtermuller et al., 1974).However, serum gastrin concentration was not altered during these investigations.This study was undertaken to define the effect of the ingestion of a neutral calcium salt on gastric acid production and serum gastrin concentration in man.The acid and gastrin response to a single oral dose at neutral pH of calcium gluconate or magnesium sulphate was assessed. Method SU BJECTSTwenty-three healthy male volunteers aged between
Is relational complexity a useful metric for cognitive development?
Authors: Usha Goswami
Journal: Behavioral and Brain Sciences (1998)

This commentary focusses on the evidence used by Halford et al. to support their postulated links between relational complexity and age differences in children's understanding of concepts. None of their developmental claims is consistent with recent cognitive-developmental research. Relational complexity must be an important variable in cognition, but it does not provide a satisfactory metric for explaining cognitive development.
The Search for Safer Glucocorticoid Receptor Ligands
Authors: Jonathan Rosen, Jeffrey N. Miner
Journal: Endocrine Reviews (2005)

Steroidal glucocorticoids are commonly used due to their powerful antiinflammatory activity. However, despite their excellent efficacy, severe side effects frequently limit the use of these drugs. The search for novel glucocorticoids with reduced side effects has been intensified by the discovery of new molecular details regarding the function of the glucocorticoid receptor. These new insights may pave the way for novel, safer therapies that retain the efficacy of currently prescribed steroids.
Prostate-Specific Antigen-Activated Thapsigargin Prodrug as Targeted Therapy for Prostate Cancer
Authors: S. R. Denmeade, C. M. Jakobsen, S. Janssen, S. R. Khan, E. S. Garrett, H. Lilja, S. B. Christensen, J. T. Isaacs
Journal: JNCI Journal of the National Cancer Institute (2003)

Standard anti-proliferative chemotherapy is relatively ineffective against slowly proliferating androgen-independent prostate cancer cells within metastatic sites. In contrast, the lipophilic cytotoxin thapsigargin, which causes apoptosis by disrupting intracellular free Ca2+ levels, is effective against both proliferative and quiescent (i.e., G0-arrested) cells. However, thapsigargin's mechanism of action indicates that it is unlikely to be selective for cancer cells or prostate cells.We coupled a chemically modified form of thapsigargin, L12ADT, to a peptide carrier that is a substrate for the prostate-specific antigen (PSA) protease to produce a soluble, cell-impermeant latent prodrug that is specifically activated extracellularly within metastatic prostate cancer sites by PSA. We analyzed the kinetics of PSA hydrolysis of the prodrug, the in vitro cytotoxicity of the prodrug against PSA-producing LNCaP human prostate cancer and PSA non-producing HCT-116 human colon cancer cells, and the in vivo pharmacokinetics of the prodrug in mice. We also analyzed antitumor efficacy of the prodrug in nude mice xenograft models of prostate cancer (using LNCaP cells) and renal carcinoma (using human SN12C cells).The L12ADT peptide prodrug was hydrolyzed efficiently by PSA, was selectively toxic to PSA-producing prostate cancer cells in vitro, and was stable in human plasma. A single dose of 7 mg/kg resulted in a peak serum prodrug concentration of 15.4 +/- 1.1 microM and a half-life of approximately 2.8 hours. Over 24 hours, less than 0.5% of free L12ADT was observed in plasma. Levels of prodrug and liberated L12ADT in prostate cancer xenograft tumors were approximately eightfold and sixfold, respectively, higher than the in vitro LD50s. Prostate cancer xenograft tumors in mice treated with prodrug by intravenous administration were growth-inhibited without substantial host toxicity. Continuous subcutaneous prodrug administration in mice produced complete growth inhibition of established PSA-producing prostate cancer xenograft tumors but had no effect on PSA non-producing renal carcinoma xenograft tumors.Further development of PSA-activated thapsigargin prodrugs as therapy for metastatic prostate cancer is warranted.
Functional characterization of a signal transducing motif present in the T cell antigen receptor zeta chain.
Authors: B A Irving, A C Chan, A Weiss
Journal: The Journal of Experimental Medicine (1993)

A conserved sequence motif has been identified in a number of signaling subunits associated with hematopoietic cell antigen receptors. Here, we characterize signaling by a 17 amino acid motif that is triplicated in the T cell antigen receptor zeta chain. Analysis of zeta truncations and constructs containing the isolated motif demonstrates that this motif is sufficient for the induction of both proximal and distal events associated with T cell activation. Stimulation of truncations that contain either one, two, or three copies of the motif results in induction of an identical pattern of tyrosine phosphoproteins. Moreover, triplication of the NH2-terminal zeta motif results in enhanced signaling, suggesting a redundant role in signal amplification for the three motifs in zeta. Finally, we demonstrate the association of a recently identified protein tyrosine kinase ZAP-70 with this motif, and provide evidence for its involvement in zeta function.
Tumor-Induced Expansion of Regulatory T Cells by Conversion of CD4+CD25− Lymphocytes Is Thymus and Proliferation Independent
Authors: Barbara Valzasina, Silvia Piconese, Cristiana Guiducci, Mario P. Colombo
Journal: Cancer Research (2006)

Abstract The CD25− and CD25+ CD4 T-lymphocyte compartments are tightly regulated. We show here that tumors break such balance, increasing the number of CD4+CD25+ T cells in draining lymph node and spleen but not contralateral node of tumor-bearing mice. Tumor injection in thymectomized and CD25-depleted mice shows that CD4+CD25+ T-cell expansion occurs even in the absence of the thymus and independently from proliferation of preexisting CD25+ T cells. These newly generated cells are bona fide regulatory T cells (T reg) in terms of Foxp3 expression and suppression of CD3-stimulated or allogeneic effector cell proliferation. Transfer of congenic Thy1.1 CD4+CD25− T cells, from mice treated or not with vinblastine, into tumor-bearing or tumor-free mice and analysis of recovered donor lymphocytes indicate that conversion is the main mechanism for acquiring the expression of CD25 and Foxp3 through a process that does not require proliferation. Although conversion of CD4+CD25− T cells for generation of T regs has been described as a natural process that maintains peripheral T-reg population, this process is used by the tumor for immune escape. The prompt recovery of T regs from monoclonal antibody–mediated CD25 depletion in tumor-bearing mice suggests attempts able to inactivate rather than deplete them when treating existing tumors. (Cancer Res 2006; 66(8): 4488-95)
Survival of Patients with Stage IV Lung Cancer with Diabetes Treated with Metformin
Authors: Jenny J. Lin, Emily J. Gallagher, Keith Sigel, Grace Mhango, Matthew D. Galsky, Cardinale B. Smith, Derek LeRoith, Juan P. Wisnivesky
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Prior studies have shown an anticancer effect of metformin in patients with breast and colorectal cancer. It is unclear, however, whether metformin has a mortality benefit in lung cancer.Objectives: To compare overall survival of patients with diabetes with stage IV non–small cell lung cancer (NSCLC) taking metformin versus those not on metformin.Methods: Using data from the Surveillance, Epidemiology, and End Results registry linked to Medicare claims, we identified 750 patients with diabetes 65–80 years of age diagnosed with stage IV NSCLC between 2007 and 2009. We used propensity score methods to assess the association of metformin use with overall survival while controlling for potential confounders.Measurements and Main Results: Overall, 61% of patients were on metformin at the time of lung cancer diagnosis. Median survival in the metformin group was 5 months, compared with 3 months in patients not treated with metformin (P < 0.001). Propensity score analyses showed that metformin use was associated with a statistically significant improvement in survival (hazard ratio, 0.80; 95% confidence interval, 0.71–0.89), after controlling for sociodemographics, diabetes severity, other diabetes medications, cancer characteristics, and treatment.Conclusions: Metformin is associated with improved survival among patients with diabetes with stage IV NSCLC, suggesting a potential anticancer effect. Further research should evaluate plausible biologic mechanisms and test the effect of metformin in prospective clinical trials.
The effects of splenectomy and glucocorticoids on survival and hepatic uptake of damaged red cells in the mouse
Authors: D. J. Ganick, G. B. Segel, J. Chamberlain, L. Hirsch, M. R. Klemperer
Journal: American Journal of Hematology (1977)

Abstract We have studied the effects of splenectomy and glucocorticoids on the survival and sequestration of Heinz body‐containing red blood cells (RBC‐HZB). Mice were injected with phenylhydrazine damaged 51 Cr labeled isologous red blood cells (RBCs). The spleen removed 36% and the liver 19% of the injected dose after 120 hrs. Red cell survival (T½) fell from 180 hrs for undamaged red cells to 16 hrs for RBC‐HZB. Splenectomy resulted in an increase in hepatic uptake of damaged RBCs (36% of the injected dose) and a modest improvement in red cell survival (T½ 54 hrs). Treatment of non‐splenectomized mice with glucocorticoids reduced the splenic uptake to 16% and the hepatic uptake to 14% of the injected dose. The reduction of splenic uptake was associated with a decrease in splenic mass rather than a decrease in uptake per unit weight of splenic tissue, while the reduction in hepatic uptake was associated with both a decrease in hepatic mass and uptake per unit weight. A marked decrease was observed in hepatic uptake and in phagocytosis by Kupffer cells in glucocorticoid‐treated splenectomized mice. These data suggest that increased hepatic uptake may decrease the effectiveness of splenectomy in RBC‐HZB hemolytic anemia and that glucocorticoids may decrease the hepatic uptake by reducing phagocytosis by Kupffer cells.
Differential expression of junctional adhesion molecules in systemic sclerosis (SSc) skin
Authors: S. Guiducci, M. Manetti, A. F. Milia, E. Romano, C. Ceccarelli, L. Ibba-Manneschi, M. Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> Junctional adhesion molecule (JAM)-A and JAM-C regulate leucocyte-endothelial cell (EC) interactions. JAMs also interact at inter-EC junctions regulating vascular permeability and are implicated in pathophysiological processes involving leucocyte transmigration, tight junction assembly and angiogenesis. SSc is characterised by early perivascular inflammatory infiltrates, EC damage and defective angiogenesis. We investigated the expression of JAMs in SSc skin and dermal microvascular ECs (MVECs) challenged with SSc sera. <h3>Methods</h3> Skin biopsies were obtained from the involved skin of 16 SSc patients (10 early, 6 late phase) and from 10 controls. Skin sections were stained with primary antibodies (Abs) anti-human JAM-A or JAM-C followed by fluorochrome-conjugated secondary Abs. The lymphatic EC specific marker podoplanin (D2-40) was used to differentiate blood (D2-40–) and lymphatic (D2-40+) vessels. Human dermal MVECs were stimulated with VEGF or early SSc (n=5) and control (n=4) sera for 1, 6, 24 h. MVECs were double-immunolabeled for JAM-C and the human tight junction protein zonula occludens-1 (ZO-1), or for JAM-A and the pro-angiogenic αVβ3 integrin. Immunostained tissue sections and cells were examined by confocal laser scanning microscopy. Densitometric analysis of staining intensity was performed using ImageJ software. <h3>Results</h3> In control skin, constitutive expression of JAM-A was observed in blood and lymphatic ECs, fibroblasts and keratinocytes. In early SSc skin, JAM-A expression was increased in blood and lymphatic vessels and fibroblasts. Moreover, perivascular inflammatory cells showed strong JAM-A positivity. In late SSc, JAM-A expression was weaker than in controls. JAM-C was weakly expressed in controls. In early SSc, JAM-C expression was markedly observed in blood and lymphatic ECs, fibroblasts, and inflammatory cells. Instead, in late SSc JAM-C expression was similar to controls. Stimulation of MVECs with early SSc sera increased the cell surface expression of JAM-A and αVβ3 integrin. JAM-C expression was found in MVEC cytoplasm at basal conditions and under stimulation with control sera. Upon early SSc sera challenging, JAM-C was rapidly recruited to tight junctions where it colocalised with ZO-1, with the maximun effect after 1 h. Similar effects were observed after 1 h VEGF stimulation. <h3>Conclusions</h3> JAMs are differentially expressed in early and late SSc skin. Early SSc sera affect the expression and subcellular localisation of JAMs in dermal MVECs. In SSc, JAMs may participate in early inflammatory process, EC activation and impaired angiogenesis.
Pneumatosis cystoides intestinalis.
Authors: D T Hughes, K C Gordon, J C Swann, G L Bolt
Journal: Gut (1966)

EDITORIAL COMMENT The association with respiratory disease is further confirmed in this detailed study.The mechanism and its production is still uncertain.The condition tends to run a benign course.There have been several recent accounts of this unusual condition in which gas-filled cysts are found subserosally and submucosally in the small and large bowel (Koss, 1952; Marshak et al., 1956; Burn and Jones, 1961; Colquohoun, 1965).Patients may present with symptoms ranging from intermittent mild rectal bleeding to intestinal obstruction, though occasionally the condition is symptomless and only revealed by radiological examination.The exact mechanism whereby cysts are formed is uncertain, but they are often found in association with disease elsewhere in the gastrointestinal tract.It has also been pointed out that they can occur in the presence of chronic pulmonary disease (Doub and Shea, 1960; Keyting, McCarver, Kovarik, and Daywitt, 1961; Kenney, 1963) and there has been speculation on their possible relationship to changes in blood gas tensions.Analysis in vivo of some components of the cyst gas has been carried out (Mujahed and Evans, 1958) and other authors have analysed contents after death with a wide range of results (Sauser-Hall, 1940;Mackenzie, 1951;Bilger, 1956).This paper presents five cases, four with pulmonary disease; all had simple pulmonary function tests performed and in one an accurate analysis of the cyst gas was made. MATERIALS AND METHODSConventional straight radiographs of chest and abdomen were taken and barium studies of the bowel were carried out using Micropaque.Lung function tests were performed using the techniques normally employed in the Lung Function Laboratory at The London Hospital (Hughes and Lee, 1963).In addition, the maximum expiratory flow rates were determined by the method described by Kory, Callahan, Boren, and Syner (1961).This should exceed 200 1./min.at any age up to 70 years, values below indicat- ing some degree of obstructive airways disease.In analysing samples of gas from the cysts in case 4 the mass spectrometer was used for estimating nitrogen and hydro-gen, an infra-red spectrometer for nitrous oxide and carbon dioxide, and gas chromatography for the remainder and to check the hydrogen value.CASE REPORTS CASE 1 B.B. was a 54-year-old man who had suffered from generalized scleroderma for 11 years.Five years previously, when he had complained of dysphagia, a FIG. 1. Detail ofstraight radiograph ofabdomen showing pneumoperitoneum, basal fibrosis at right lung base,numerous radiolucent cysts in the small bowel, some loops of which are interposed between the liver and diaphragm (case 1).