tbuckley/cabot-search huggingface dataset:
Contribution of Nerve-Axon Reflex-Related Vasodilation to the Total Skin Vasodilation in Diabetic Patients With and Without Neuropathy
Authors: Osama Hamdy, Karim Abou-Elenin, Frank W. LoGerfo, Edward S. Horton, Aristidis Veves
Journal: Diabetes Care (2001)

To examine the contribution of nerve-axon reflex-related vasodilation to total acetylcholine-induced vasodilation in the skin of normal and diabetic subjects.The skin microcirculation was evaluated at the forearm level in 69 healthy subjects and 42 nonneuropathic diabetic patients and at the foot level in 27 healthy subjects and 101 diabetic patients (33 with neuropathy, 23 with Charcot arthropathy, 32 with peripheral vascular disease and neuropathy, and 13 without complications). Two single-point laser probes were used to measure total and neurovascular vasodilation response to the iontophoresis of 1% acetylcholine, 1% sodium nitroprusside, and deionized water.The neurovascular response to acetylcholine was significantly higher than the response to sodium nitroprusside and deionized water (P < 0.01). At the forearm level, the contribution of neurovascular response to the total response to acetylcholine was 35% in diabetic patients and 31% in control subjects. At the foot level, the contribution was 29% in diabetic patients without neuropathy and 36% in control subjects, while it was significantly diminished in the three neuropathic groups. A significantly lower nonspecific nerve-axon-related vasodilation was observed during the iontophoresis of sodium nitroprusside, which does not specifically stimulate the C nociceptive fibers.Neurovascular vasodilation accounts for approximately one-third of the total acetylcholine-induced vasodilation at both the forearm and foot levels. The presence of diabetic neuropathy results in reduction of both the total vasodilatory response to acetylcholine and the percentage contribution of neurovascular vasodilation to the total response. Acetylcholine and sodium nitroprusside cause vasodilation in the skin microcirculation through different pathways.
TGF-β Signaling in Myeloid Cells Is Required for Tumor Metastasis
Authors: Yanli Pang, Sudheer Kumar Gara, Bhagelu R. Achyut, Zhaoyang Li, Hannah H. Yan, Chi-Ping Day, Jonathan M. Weiss, Giorgio Trinchieri, John C. Morris, Li Yang
Journal: Cancer Discovery (2013)

TGF-β is overexpressed in advanced human cancers. It correlates with metastasis and poor prognosis. However, TGF-β functions as both a tumor suppressor and a tumor promoter. Here, we report for the first time that genetic deletion of Tgfbr2 specifically in myeloid cells (Tgfbr2(MyeKO)) significantly inhibited tumor metastasis. Reconstitution of tumor-bearing mice with Tgfbr2(MyeKO) bone marrow recapitulated the inhibited metastasis phenotype. This effect is mediated through decreased production of type II cytokines, TGF-β1, arginase 1, and inducible nitric oxide synthase, which promoted IFN-γ production and improved systemic immunity. Depletion of CD8 T cells diminished the metastasis defect in the Tgfbr2(MyeKO) mice. Consistent with animal studies, myeloid cells from patients with advanced-stage cancer showed increased TGF-β receptor II expression. Our studies show that myeloid-specific TGF-β signaling is an essential component of the metastasis-promoting puzzle of TGF-β. This is in contrast to the previously reported tumor-suppressing phenotypes in fibroblasts, epithelial cells, and T cells.
MUC1 Oncoprotein Promotes Refractoriness to Chemotherapy in Thyroid Cancer Cells
Authors: Mauro Siragusa, Monica Zerilli, Flora Iovino, Maria Giovanna Francipane, Ylenia Lombardo, Lucia Ricci-Vitiani, Giuseppe Di Gesù, Matilde Todaro, Ruggero De Maria, Giorgio Stassi
Journal: Cancer Research (2007)

Abstract Overexpression of MUC1 oncoprotein is frequently observed in cancer and contributes to confer resistance to genotoxic agents. Papillary, follicular, and anaplastic thyroid carcinomas are the three forms of thyroid epithelial cancer. Anaplastic tumors are less differentiated and extremely aggressive, characterized by a poor prognosis. Little is known about the role of MUC1 in thyroid cancer. We recently showed that autocrine production of interleukin (IL)-4 and IL-10 controls thyroid cancer cell survival, growth, and resistance to chemotherapy through activation of Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) and phosphatidylinositide 3′-OH kinase (PI3K)/Akt pathways. In the present study, we showed that MUC1 COOH-terminal subunit (MUC1-C) is overexpressed in all the histologic variants of thyroid cancer cells and localizes to mitochondria where it interferes with the release of mitochondrial proapoptotic proteins. Moreover, IL-4 and IL-10 promote the increase of MUC1-C expression levels in normal thyroid cells, whereas blockage of both cytokines or neutralization of JAK/STAT and PI3K/Akt pathways through the exogenous expression of SOCS-1 and AktK179M leads to a significant decrease of MUC1-C in primary thyroid cancer cells. Interestingly, down-regulation of MUC1 expression by direct targeting with RNA interference sensitizes anaplastic thyroid cancer cells to chemotherapy-induced apoptosis in vitro. Thus, MUC1 is a main component of the survival network acting in thyroid cancer and could be considered a key molecular target for sensitizing cancer cells to conventional or novel treatments. [Cancer Res 2007;67(11):5522–30]
The Relationship Between Timing of Surgical Complications and Hospital Readmission
Authors: Melanie S. Morris, Rhiannon J. Deierhoi, Joshua S. Richman, Laura K. Altom, Mary T. Hawn
Journal: JAMA Surgery (2014)

Readmissions after surgery are costly and may reflect quality of care in the index hospitalization.To determine the timing of postoperative complications with respect to hospital discharge and the frequency of readmission stratified by predischarge and postdischarge occurrence of complications.This is a retrospective cohort study of national Veterans Affairs Surgical Quality Improvement Program preoperative risk and outcome data on the Surgical Care Improvement Project cohort for operations performed from January 2005 to August 2009, including colorectal, arthroplasty, vascular, and gynecologic procedures. The association between timing of complication with respect to index hospitalization and 30-day readmission was modeled using generalized estimating equations.All-cause readmission within 30 days of the index surgical hospitalization discharge. RESULTS Our study of 59 273 surgical procedures performed at 112 Department of Veterans Affairs (VA) hospitals found an overall complication rate of 22.6% (predischarge complications, 71.9%; postdischarge complications, 28.1%). The proportion of postdischarge complications varied significantly, from 8.7% for respiratory complications to 55.7% for surgical site infection (P < .001). The overall 30-day readmission rate was 11.9%, of which only 56.0% of readmissions were associated with a currently assessed complication. Readmission was predicted by patient comorbid conditions, procedure factors, and the occurrence of postoperative complications. Multivariable generalized estimating equation models of readmission adjusting for patient and procedure characteristics, hospital, and index length of stay found that the occurrence of postdischarge complications had the highest odds of readmission (odds ratio, 7.4-20.8) compared with predischarge complications (odds ratio, 0.9-1.48).More than one-quarter of assessed complications are diagnosed after hospital discharge and strongly predict readmission. Hospital discharge is an insufficient end point for quality assessment. Although readmission is associated with complications, almost half of readmissions are not associated with a complication currently assessed by the Veterans Affairs Surgical Quality Improvement Program.
Evidence for a link between mortality in acute COPD and hospital type and resources
Authors: C M Roberts
Journal: Thorax (2003)

<b>Background:</b> The 1997 BTS/RCP national audit of acute care of chronic obstructive pulmonary disease (COPD) found wide variations in mortality between hospitals which were only partially explained by known audit indicators of outcome. It was hypothesised that some of the unexplained variation may result from differences in hospital type, organisation and resources. This pilot study examined the hypothesis as a factor to be included in a future national audit programme. <b>Methods:</b> Thirty hospitals in England and Wales were randomly selected by geographical region and hospital type (teaching, large district general hospital (DGH), small DGH). Data on process and outcome of care (death and length of stay) were collected retrospectively at 90 days on all prospectively identified COPD admissions over an 8 week period. Each centre completed a questionnaire relating to organisation and resources available for the care of COPD patients. <b>Results:</b> Eleven teaching hospitals, nine large DGHs, and 10 small DGHs provided data on 1274 cases. Mortality was high (14%) with wide variation between centres (IQR 9–19%). Small DGHs had a higher mortality (17.5%) than teaching hospitals (11.9%) and large DGHs (11.2%). When corrected for confounding factors, an excess of deaths in small DGHs was still observed (OR 1.56 (CI 1.04 to 2.35)) <i>v</i> teaching hospitals. Analysis of resource and organisational factors suggested higher mortality was associated with fewer doctors (OR 1.5) and with fewer patients being under the care of a specialist physician (OR 1.8). Small DGHs had fewest resources. <b>Conclusion:</b> Significant differences in mortality may exist between hospital types. The findings justify further study in a proposed national audit.
Smooth Reference Equations for Slow Vital Capacity and Flow–Volume Curve Indexes
Authors: FRANCESCO PISTELLI, MATTEO BOTTAI, GIOVANNI VIEGI, FRANCESCO DI PEDE, LAURA CARROZZI, SANDRA BALDACCI, MARZIA PEDRESCHI, CARLO GIUNTINI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We derived reference values for slow vital capacity (VC) and flow-volume curve indexes (FVC, FEV(1), and flows) from the 1,185 tracings provided by 1,039 "normal" subjects who participated in one or both cross-sectional surveys of the Po River Delta study in 1980-1982 and in 1988-1991. Definition of "normal" was based on negative answers to questions on respiratory symptoms/diseases or recent infections, current/past tobacco smoking, and work exposure to noxious agents. Reference equations were derived separately by sex as linear regressions of body mass index (BMI = weight/height(2)), BMI-squared, height, height-squared, and age. Age entered all the models by natural cubic splines using two break points, except for the ratios FEV(1)/VC and FEV(1)/FVC. Random effects models were applied to adjust for the potential intrasubject correlation. BMI, along with height and age, appeared to be an important predictor, which was significantly associated with VC, FEV(1), FVC, FEV(1)/FVC, and PEF in both sexes, and with FEV(1)/VC and FEF(25-75) in females. Natural cubic splines provided smooth reference equation curves (no "jumps" or "angled points") over the entire age span, differently from the conventional reference equations. Thus, we recommend the use of smooth continuous equations for predicting lung function indexes, along with the inclusion of BMI in the equations.
Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblastlike cells. A potential mechanism of self perpetuation in liver fibrogenesis.
Authors: M G Bachem, D Meyer, R Melchior, K M Sell, A M Gressner
Journal: Journal of Clinical Investigation (1992)

Rat liver perisinusoidal lipocytes (PL) cultured on uncoated plastic transform spontaneously within 6-10 d to myofibroblastlike cells (MFBlC). Parallel to the transformation the TGF alpha- and TGF beta 1-mRNA expression increased and was highest in MFBlC. Competitive radioligand binding assays demonstrated that in contrast to untransformed PL the MFBlC synthesize and secrete transforming growth factor (TGF)-alpha (15 fmol/cell per 24 h) and predominantly the latent form of TGF beta 1 (0.2 fmol/cell per 24 h). Medium conditioned by MFBlC (MFBcM) significantly stimulated PL proliferation with little effect on PL proteoglycan synthesis. By transient acidification of the MFBcM, known to activate the latent form of TGF beta 1, the stimulatory effect on PL proteoglycan synthesis was enhanced and furthermore PL transformation (measured by expression of iso-alpha smooth muscle actin and loss of retinylpalmitate) was accelerated. Preincubation of this medium with neutralizing antibodies to TGF beta resulted in (a) the growth inhibitory effect was converted to a growth stimulation and (b) the stimulatory effect on proteoglycan synthesis was abolished. In summary our data indicate that progressive activation of PL on plastic (transformation to MFBlC) leads to an enhanced expression of the TGF alpha- and TGF beta 1-mRNAs and secretion of the corresponding proteins. Medium conditioned by MFBIC stimulates proliferation, transformation, and PG synthesis of untransformed PL. These mechanisms are suggested to be relevant in self perpetuation of liver fibrogenesis.
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Authors: Peter J. Becci, Elizabeth M. McDowell, Benjamin F. Trump
Journal: JNCI Journal of the National Cancer Institute (1978)

The histogenesis of epidermoid metaplasia and carcinoma in situ was analyzed in human bronchial epithelium. The conclusion is that epidermoid metaplasia and carcinoma in situ can result from conversion of mucous cells. This implies the direct transformation of one type of fully differentiated cell to another. The study therefore emphasizes the differentiation potentialities of the mucous cells that can divide and undergo goblet cell hyperplasia and epidermoid metaplasia. Epidermoid metaplasia is a common reaction to injury in the bronchus. In our series of cases it was especially frequent in patients without neoplastic disease who had undergone intratracheal intubation or tracheostomy and who had been maintained on a respirator in the Shock Trauma Unit, University of Maryland. Future studies will be required to distinguish the difference, if any, between epidermoid metaplasia destined to become malignant carcinoma and that which is not. One difference noted in this study was the absence of overt cornification in epidermoid metaplasia in patients without neoplastic disease.
The Effect of Changing Patterns of Obstetric Care in Scotland (1980–2004) on Rates of Preterm Birth and Its Neonatal Consequences: Perinatal Database Study
Authors: Jane E. Norman, Carole Morris, James Chalmers
Journal: PLoS Medicine (2009)

Rates of preterm birth are rising worldwide. Studies from the United States and Latin America suggest that much of this rise relates to increased rates of medically indicated preterm birth. In contrast, European and Australian data suggest that increases in spontaneous preterm labour also play a role. We aimed, in a population-based database of 5 million people, to determine the temporal trends and obstetric antecedents of singleton preterm birth and its associated neonatal mortality and morbidity for the period 1980-2004.There were 1.49 million births in Scotland over the study period, of which 5.8% were preterm. We found a percentage increase in crude rates of both spontaneous preterm birth per 1,000 singleton births (10.7%, p<0.01) and medically indicated preterm births (41.2%, p<0.01), which persisted when adjusted for maternal age at delivery. The greater proportion of spontaneous preterm births meant that the absolute increase in rates of preterm birth in each category were similar. Of specific maternal complications, essential and pregnancy-induced hypertension, pre-eclampsia, and placenta praevia played a decreasing role in preterm birth over the study period, with gestational and pre-existing diabetes playing an increasing role. There was a decline in stillbirth, neonatal, and extended perinatal mortality associated with preterm birth at all gestation over the study period but an increase in the rate of prolonged hospital stay for the neonate. Neonatal mortality improved in all subgroups, regardless of obstetric antecedent of preterm birth or gestational age. In the 28 wk and greater gestational groups we found a reduction in stillbirths and extended perinatal mortality for medically induced but not spontaneous preterm births (in the absence of maternal complications) although at the expense of a longer stay in neonatal intensive care. This improvement in stillbirth and neonatal mortality supports the decision making behind the 34% increase in elective/induced preterm birth in these women. Although improvements in neonatal outcomes overall are welcome, preterm birth still accounts for over 66% of singleton stillbirths, 65% of singleton neonatal deaths, and 67% of infants whose stay in the neonatal unit is "prolonged," suggesting this condition remains a significant contributor to perinatal mortality and morbidity.In our population, increases in spontaneous and medically induced preterm births have made equal contributions to the rising rate of preterm birth. Despite improvements in related perinatal mortality, preterm birth remains a major obstetric and neonatal problem, and its frequency is increasing. Please see later in the article for the Editors' Summary.
FHL2/SLIM3 Decreases Cardiomyocyte Survival by Inhibitory Interaction With Sphingosine Kinase-1
Authors: Jianxin Sun, Guijun Yan, Aixia Ren, Bei You, James K. Liao
Journal: Circulation Research (2006)

Sphingosine kinase-1 (SK1) is a key enzyme catalyzing the phosphorylation of sphingosine to sphingosine-1–phosphate (S1P). Recent studies suggest that SK1, and its product S1P, regulate diverse biological functions, including cell growth, differentiation, proliferation, and apoptosis. S1P may also play an important role in cardiac development and ischemic preconditioning, but the mechanism underlying these effects is not known. Using a yeast 2-hybrid screen with SK1 as bait and a cardiac cDNA library to identify novel proteins involved in regulating SK1 activity in cardiomyocytes, we identified the LIM-only factor FHL2 (SLIM3) as a SK1-interacting protein in both yeast and mammalian cells. FHL2, but not FHL1 or FHL3, interacted with SK1, and FHL2 colocalized with SK1 in the cytoplasm. The interaction sites with SK1 consisted of at least 4 LIM domains in FHL2, whereas the C-terminal portion of SK1 mediates the binding of FHL2 in SK1. Overexpression of FHL2 attenuated the activity and antiapoptotic effects of SK1. Indeed, endothelin-1, which is a potent survival factor in cardiomyocytes, inhibited FHL2-SK1 association and increased SK1 activity. These findings indicate that FHL2 is a novel inhibitor of SK1 activity in cardiomyocytes and suggest that targeting FHL2 for inhibition may prevent myocardial apoptosis through activation of SK1.
The Adaptable Major Histocompatibility Complex (MHC) Fold: Structure and Function of Nonclassical and MHC Class I–Like Molecules
Authors: Erin J. Adams, Adrienne M. Luoma
Journal: Annual Review of Immunology (2013)

The MHC fold is found in proteins that have a range of functions in the maintenance of an organism's health, from immune regulation to fat metabolism. Well adapted for antigen presentation, as seen for peptides in the classical MHC molecules and for lipids in CD1 molecules, the MHC fold has also been modified to perform Fc-receptor activity (e.g., FcRn) and for roles in host homeostasis (e.g., with HFE and ZAG). The more divergent MHC-like molecules, such as some of those that interact with the NKG2D receptor, represent the minimal MHC fold, doing away with the α3 domain and β 2 m while maintaining the α1/α2 platform domain for receptor engagement. Viruses have also co-opted the MHC fold for immune-evasive functions. The variations on the theme of a β-sheet topped by two semiparallel α-helices are discussed in this review, highlighting the fantastic adaptability of this fold for good and for bad.
Maternal and Perinatal Outcomes Associated with a Trial of Labor after Prior Cesarean Delivery
Authors: Mark B. Landon, John C. Hauth, Kenneth J. Leveno, Catherine Y. Spong, Sharon Leindecker, Michael W. Varner, Atef H. Moawad, Steve N. Caritis, Margaret Harper, Ronald J. Wapner, Yoram Sorokin, Menachem Miodovnik, Marshall Carpenter, Alan M. Peaceman, Mary Jo O'Sullivan, Baha Sibai, Oded Langer, John M. Thorp, Susan M. Ramin, Brian M. Mercer, Steven G. Gabbe
Journal: New England Journal of Medicine (2004)

The proportion of women who attempt vaginal delivery after prior cesarean delivery has decreased largely because of concern about safety. The absolute and relative risks associated with a trial of labor in women with a history of cesarean delivery, as compared with elective repeated cesarean delivery without labor, are uncertain.
Identification of GRP75 as an Independent Favorable Prognostic Marker of Neuroblastoma by a Proteomics Analysis
Authors: Wen-Ming Hsu, Hsinyu Lee, Hsueh-Fen Juan, Yu-Yin Shih, Bo-Jeng Wang, Chien-Yuan Pan, Yung-Ming Jeng, Hsiu-Hao Chang, Meng-Yao Lu, Kai-Hsin Lin, Hong-Shiee Lai, Wei-Jao Chen, Yeou-Guang Tsay, Yung-Feng Liao, Fon-Jou Hsieh
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Neuroblastoma (NB) is a heterogeneous neoplasm. Detailed biological discrimination is critical for the effective treatment of this disease. Because the tumor behavior of NB is closely associated with the histologic state of differentiation, we thus aimed to identify novel differentiation-associated markers of NB with prognostic implication. Experimental Design: A human NB cell line SH-SY5Y was used as a model system to explore potential biomarkers for the differentiation of NB by proteomic analyses. Seventy-two NB tumor tissues were subsequently investigated by immunohistochemistry to validate the correlations between the expression of a novel prognostic marker, various clinicopathologic and biological factors, and patient survival. Results: Using two-dimensional differential gel electrophoresis, we found a total of 24 spots of proteins in SH-SY5Y cells whose expression was enhanced following differentiation. Glucose-regulated protein 75 (GRP75) was unambiguously identified as one of the five proteins that were dramatically up-regulated following differentiation. Immunohistochemical analyses of 72 NB tumor tissues further revealed that positive GRP75 immunostaining is strongly correlated with differentiated histologies (P &amp;lt; 0.001), mass-screened tumors (P = 0.016), and early clinical stages (P &amp;lt; 0.001) but inversely correlated with MYCN amplification (P = 0.010). Univariate and multivariate survival analyses showed that GRP75 expression is an independent favorable prognostic factor. Conclusions: The present findings clearly showed that our proteomics-based novel experimental paradigm could be a powerful tool to uncover novel biomarkers associated with the differentiation of NB. Our data also substantiate an essential role of GRP75 in the differentiation of NB.