tbuckley/cabot-search huggingface dataset:
Chronic Cigarette Smoke Exposure Generates Pathogenic T Cells Capable of Driving COPD-like Disease in Rag2<sup>−/−</sup> Mice
Authors: Gregory T. Motz, Bryan L. Eppert, Scott C. Wesselkamper, Jennifer L. Flury, Michael T. Borchers
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Pathogenic T cells drive, or sustain, a number of inflammatory diseases. Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with the accumulation of activated T cells. We previously demonstrated that chronic cigarette smoke (CS) exposure causes oligoclonal expansion of lung CD4+ T cells and CD8+ T cells in a mouse model of COPD, thus implicating these cells in disease pathogenesis.Objectives: To determine whether T cells are pathogenic in a CS-induced mouse model of COPD.Methods: We transferred lung CD3+ T cells from filtered air (FA)- and CS-exposed mice into Rag2−/− recipients. Endpoints associated with the COPD phenotype were then measured.Measurements and Main Results: Here, we demonstrate that chronic CS exposure generates pathogenic T cells. Transfer of CD3+ T cells from the lungs of CS-exposed mice into Rag2−/− recipients led to substantial pulmonary changes pathognomonic of COPD. These changes included monocyte/macrophage and neutrophil accumulation, increased expression of cytokines and chemokines, activation of proteases, apoptosis of alveolar epithelial cells, matrix degradation, and airspace enlargement reminiscent of emphysema.Conclusions: These data formally demonstrate, for the first time, that chronic CS exposure leads to the generation of pathogenic T cells capable of inducing COPD-like disease in Rag2−/− mice. This report provides novel insights into COPD pathogenesis.
Community-acquired Pneumonia in the Elderly
Authors: RAÚL RIQUELME, ANTONI TORRES, MUSTAFA EL-EBIARY, JOSEP MENSA, RAMÓN ESTRUCH, MAURICIO RUIZ, JOAQUIM ANGRILL, NESTOR SOLER
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Community-acquired pneumonia (CAP) in the elderly has a different clinical presentation than CAP in other age groups. Confusion, alteration of functional physical capacity, and decompensation of underlying illnesses may appear as unique manifestations. Malnutrition is also an associated feature of CAP in this population. We undertook a study to assess the clinical and nutritional aspects of CAP requiring hospitalization in elderly patients (over 65 yr of age). One hundred and one patients with pneumonia, consecutively admitted to a 1,000-bed teaching hospital over an 8-mo period, were studied (age: 78 ± 8 yr, mean ± SD). Nutritional aspects and the mental status of patients with pneumonia were compared with those of a control population (n = 101) matched for gender, age, and date of hospitalization. The main symptoms were dyspnea (n = 71), cough (n = 67), and fever (n = 64). The association of these symptoms with CAP was observed in only 32 patients. The most common associated conditions were cardiac disease (n = 38) and chronic obstructive pulmonary disease (COPD) (n = 30). Seventy-seven (76%) episodes of pneumonia were clinically classified as typical and 24 as atypical. There was no association between the type of isolated microorganism and the clinical presentation of CAP, except for pleuritic chest pain, which was more common in pneumonia episodes caused by classical microorganisms (p = 0.02). This was confirmed by a multivariate analysis (relative risk [RR] = 11; 95% confidence interval [CI]: 1.7 to 65; p = 0.0099). The prevalence of chronic dementia was similar in the pneumonia cohort (n = 25) and control group (n = 18) (p = 0.22). However, delirium or acute confusion were significantly more frequent in the pneumonia cohort than in controls (45 versus 29 episodes; p = 0.019). Only 16 patients with pneumonia were considered to be well nourished, as compared with 47 control patients (p = 0.001). Kwashiorkor-like malnutrition was the predominant type of malnutrition (n = 65; 70%) in the pneumonia patients as compared with the control patients (n = 31; 31%) (p = 0.001). The observed mortality was 26% (n = 26). Pleuritic chest pain is the only clinical symptom that can guide an empiric therapeutic strategy in CAP (typical versus atypical pneumonia). Both delirium and malnutrition were very common clinical manifestations of CAP in our study population.
Paraneoplastic Neurologic Disease Antigens: RNA-Binding Proteins and Signaling Proteins in Neuronal Degeneration
Authors: Kiran Musunuru, Robert B. Darnell
Journal: Annual Review of Neuroscience (2001)

▪ Abstract Studies of the disorders known as paraneoplastic neurologic degenerations exemplify the successful application of modern molecular biological techniques to diseases, yielding, even for these extremely rare disorders, wide-ranging insight into basic neurobiology, tumor immunity, and autoimmune neurologic disease. Immune responses to paraneoplastic neurologic degeneration antigens, also called onconeural antigens, have been exploited to clone and characterize a number of neuron-specific proteins, including several RNA-binding proteins and new kinds of signaling molecules. The biology and functions of these proteins are reviewed, and a model in which their functions are related to the pathogenesis of autoimmune neurologic disease is discussed.
A simple new technique to measure the effective dead space of the face mask with a water volumeter in infants
Authors: MG Morris
Journal: European Respiratory Journal (1999)

Measuring the effective dead space (EDS) of a face mask has been difficult in infants and the appropriate volume being deducted from lung volume measurements has varied between laboratories. This study measured EDS in 16 infants (age range, 5-36 months) who have cystic fibrosis, undergoing lung volume measurement by N2 washout. A thin plastic bladder, whose neck resided in the mask port, was shaped to fill a size 1 clear face mask. A water volumeter was made by inserting the body of a 20 mL plastic syringe into the neck of the bladder forming a tight seal with a snug fit against the inner surface of the mask port. The mask was placed on a horizontal surface and water was added until a level appeared in the syringe body (V1). At end-inspiration, the mask was briefly placed on the mouth and nose of the sleeping infant, causing the water level to rise in the syringe body (V2). The actual total dead space (V) of the mask when connected to the mouth port of the slide valve was 23 mL. EDS = V- (V2 - V1). Mean (95% confidence interval (95%CI)) EDS was 12.4 (95% CI 11.2, 13.6) mL. The smallest EDS was 8 mL since the connected ports (dead space, 8 mL) were unlikely to be penetrated by the infant's nose or lips. EDS decreased with increasing body weight and height, but seemed to be influenced by individual facial features too. In conclusion, a reliable noninvasive volumetric technique for the routine measurement of the effective dead space in infants has been developed.
Coding OSICS sports injury diagnoses in epidemiological studies: does the background of the coder matter?
Authors: Caroline F Finch, John W Orchard, Dara M Twomey, Muhammad Saad Saleem, Christina L Ekegren, David G Lloyd, Bruce C Elliott
Journal: British Journal of Sports Medicine (2012)

To compare Orchard Sports Injury Classification System (OSICS-10) sports medicine diagnoses assigned by a clinical and non-clinical coder.
Dexamethasone Destabilizes Nmyc to Inhibit the Growth of Hedgehog-Associated Medulloblastoma
Authors: Vivi M. Heine, Markus Priller, Jason Ling, David H. Rowitch, Ulrich Schüller
Journal: Cancer Research (2010)

Mouse studies indicate that the synthetic glucocorticoid dexamethasone (Dex) impairs the proliferation of granule neuron precursors in the cerebellum, which are transformed to medulloblastoma by activation of Sonic hedgehog (Shh) signaling. Here, we show that Dex treatment also inhibits Shh-induced tumor growth, enhancing the survival of tumor-prone transgenic mice. We found that Nmyc was specifically required in granule cells for Shh-induced tumorigenesis and that Dex acted to reduce Nmyc protein levels. Moreover, we found that Dex-induced destabilization of Nmyc is mediated by activation of glycogen synthase kinase 3beta, which targets Nmyc for proteasomal degradation. Together, our findings show that Dex antagonizes Shh signaling downstream of Smoothened in medulloblastoma.
Private firm beats award winning social enterprise to run NHS community services
Authors: A. O'Dowd
Journal: BMJ (2011)

An award winning social enterprise mutual has lost out to a private company that has been named as the preferred bidder to run NHS community health services in Surrey in a deal worth between £450m (€520m; $710m) and £500m.

The primary care trust NHS Surrey has announced that Assura Medical, which is owned by Virgin, is the preferred bidder for community health services in southwest and northwest Surrey in what is likely to be one of the largest NHS contracts ever given to the independent sector.

The fellow bidder Central Surrey Health lost out despite its reputation as the government’s flagship social enterprise mutual. The other unsuccessful bidder was Surrey and Borders Partnership NHS Foundation Trust.

Central Surrey Health was set up in 2006 as an employee owned, not for profit organisation that provides therapy and community …
Fetal Overnutrition in Polynesian Pregnancies and in Gestational Diabetes May Lead to Dysregulation of the Adipoinsular Axis in Offspring
Authors: David Simmons, Bernhard H. Breier
Journal: Diabetes Care (2002)

OBJECTIVE—To compare umbilical cord leptin concentrations in different ethnic groups and between pregnancies with and without gestational diabetes mellitus (GDM) in Auckland, New Zealand. RESEARCH DESIGN AND METHODS—A cross-sectional study of 116 European, Polynesian, and South Asian women and their infants with and without GDM. Maternal metabolic measures were recorded at 36 weeks’ gestation, umbilical cord samples were collected at birth, and neonatal anthropometric measures were recorded 24 h after delivery. RESULTS—Compared with Europeans and South Asians, samples of Polynesian umbilical cords had higher leptin concentrations (8.7 and 9.5 vs. 14.9 ng/ml, respectively; P = 0.026). Umbilical cord samples from pregnancies complicated by GDM had higher leptin concentrations than those from normal pregnancies (22.3 vs. 13.8 ng/ml, respectively; P = 0.022). Maternal leptin concentrations at 36 weeks were similar across ethnic groups and with and without GDM. Cord leptin correlated with birth weight, measures of fetal size, and cord insulin in normal pregnancies and those complicated by GDM. In multivariate analyses, cord leptin was related to birth weight (P &amp;lt; 0.001), gestation at delivery (P = 0.038), and ethnic group (P = 0.017) in normal pregnancies and to birth weight (P &amp;lt; 0.001), gestation at delivery (P &amp;lt; 0.001), and sex (P = 0.003) but not maternal diabetes status (P = 0.909) in pregnancies complicated by GDM. CONCLUSIONS—Offspring of Polynesian women are relatively hyperleptinemic, independent of birth size. Offspring of women with GDM are also relatively hyperleptinemic at birth, but this was associated with their increased birth weight. We speculate that this GDM-associated relative hyperleptinemia may be due to fuel-mediated teratogenesis affecting the adipoinsular axis, which in turn could also lead to leptin resistance and obesity in adult life. The reason for the ethnic difference in hyperleptinemia is unclear.
MRSA colonisation may lead to increased mortality in patients with cystic fibrosis
Authors: P. Whitaker
Journal: Thorax (2010)

The long-term impact of respiratory tract methicillin-resistant Staphylococcus aureus (MRSA) on cystic fibrosis (CF) outcomes is unclear. This cohort study used longitudinal data from the US CF registry between 1996 and 2008. The aim of the study was to assess whether acquisition of MRSA influenced mortality.

A total of 19 833 MRSA …
BILATERAL FRACTURE OF THE FIRST RIB
Authors: M. C. Oldfield
Journal: BMJ (1935)

MEDICALJOURNApresent.Large vessels were seen running along the ureter, which was freed to within an inch of the bladder, where it was doubly ligated anct divided.The kidney and proximal part of the ureter were removed, and the wound closed with drainage down to the ureteric stump.A catheter was inserted to avoid back-pressure on the ureteric stump.After operation the condition of the urine was improved, but the infection persisted although it was less severe.
Effects of isoprenaline and ouabain on cytosolic calcium and cell motion in single rat cardiomyocytes
Authors: K. Tamura, S. Yoshida, T. Iwai, I. Watanabe
Journal: Cardiovascular Research (1992)

The aim was to develop a novel system to measure changes in cytosolic free calcium concentration ([Ca2+]i) and cell motion simultaneously in a single beating myocyte by digital imaging microscopy.Indo-1 was selected as a fluorescent calcium indicator. The particular feature of our digital imaging microscopy is that, in order to avoid cell movement artifacts, two indo-1 fluorescence images of different wavelengths are obtained at the same time at 16.7 ms intervals using two SIT cameras. Isolated ventricular myocytes were used, prepared from hearts of male Sprague-Dawley rats, weighing 350 to 400 g.In continuously beating cells contracted by electrical field stimulation, we can visualise changes in [Ca2+]i and cell shape during contraction with pseudocolour images of the fluorescence ratios, and it was found that the onset of the calcium transient preceded that of the shortening of cell length. Both isoprenaline and ouabain enhanced the magnitudes of the calcium transient and cell contraction. Furthermore, isoprenaline shortened the half decay time of the calcium transient.Our data suggest that the newly developed system is useful for measuring rapid changes in [Ca2+]i in relation to cell motion, and is particularly suitable for measuring the calcium transients in a beating cardiomyocyte.
Immune Cell-Mediated Antitumor Activities of GD2-Targeted Liposomal c-myb Antisense Oligonucleotides Containing CpG Motifs
Authors: C. Brignole, F. Pastorino, D. Marimpietri, G. Pagnan, A. Pistorio, T. M. Allen, V. Pistoia, M. Ponzoni
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Expression of the c-myb proto-oncogene in neuroblastoma, the most common extracranial solid tumor of infancy, is linked with cell proliferation and differentiation. Neuroblastoma can be selectively targeted via monoclonal antibodies against the disialoganglioside (GD 2 ) tumor-associated antigen. Liposomes coated with anti-GD 2 antibodies (targeted liposomes) and entrapping a c-myb antisense oligonucleotide have antitumor activity. Because antisense oligonucleotides containing CpG motifs can stimulate immune responses, we evaluated the effect of CpG-containing c-myb antisense oligonucleotides encapsulated within targeted liposomes. Methods: Antisense (myb-as) and scrambled (myb-scr) control oligonucleotides with CpG motifs were encapsulated within GD 2 -targeted and non-targeted liposomes. Two murine (nude and SCID-bg) xenograft models of neuroblastoma were established. Mice (groups of 10) were injected intravenously with various oligonucleotide and liposome formulations, and life span, long-term survival, immune cell activation, and cytokine release were measured over time. Results: Tumor-bearing mice injected with targeted liposome-CpG-myb-as or targeted liposome-CpG-myb-scr lived longer than mice in any other group, although long-term survival (i.e., more than 120 days) was obtained only in mice injected with targeted liposome-CpG-myb-as. Splenocytes isolated from mice injected with targeted liposome-CpG-myb-as contained activated macrophages, B cells, and natural killer (NK) cells, but only activated NK cells were associated with antitumor cytotoxic activity. In vivo immune cell activation was accompanied by the time-dependent increases in plasma levels of the cytokines interleukin 12 (IL-12; maximum level reached by 2 hours) and interferon gamma (IFN-γ; maximum level reached by 18 hours) and was dependent on the oligonucleotide CpG motif. Ablation of macrophages or NK cells resulted in a loss of in vivo antitumor activity. Conclusion: Immune cell activation, involving the time-dependent activation of macrophages and NK cells, contributes to the antitumor activity of targeted liposome-CpG-myb-as against neuroblastoma and could improve the effectiveness of antitumor targeted liposomes.
Evolution of Interacting Proteins in the Mitochondrial Electron Transport System in a Marine Copepod
Authors: Christopher S. Willett, Ronald S. Burton
Journal: Molecular Biology and Evolution (2004)

The extensive interaction between mitochondrial-encoded and nuclear-encoded subunits of electron transport system (ETS) enzymes in mitochondria is expected to lead to intergenomic coadaptation. Whether this coadaptation results from adaptation to the environment or from fixation of deleterious mtDNA mutations followed by compensatory nuclear gene evolution is unknown. The intertidal copepod Tigriopus californicus shows extreme divergence in mtDNA sequence and provides an excellent model system for study of intergenomic coadaptation. Here, we examine genes encoding subunits of complex III of the ETS, including the mtDNA-encoded cytochrome b (CYTB), the nuclear-encoded rieske iron-sulfur protein (RISP), and cytochrome c1 (CYC1). We compare levels of polymorphism within populations and divergence between populations in these genes to begin to untangle the selective forces that have shaped evolution in these genes. CYTB displays dramatic divergence between populations, but sequence analysis shows no evidence for positive selection driving this divergence. CYC1 and RISP have lower levels of sequence divergence between populations than CYTB, but, again, sequence analysis gives no evidence for positive selection acting on them. However, an examination of variation at cytochrome c (CYC), a nuclear-encoded protein that transfers electrons between complex III and complex IV provides evidence for selective divergence. Hence, it appears that rapid evolution in mitochondrial-encoded subunits is not always associated with rapid divergence in interacting subunits (CYC1 and RISP), but can be in some cases (CYC). Finally, a comparison of nuclear-encoded and mitochondrial-encoded genes from T. californicus suggests that substitution rates in the mitochondrial-encoded genes are dramatically increased relative to nuclear genes.
Cholesterol Metabolism After Bariatric Surgery in Grade 3 Obesity
Authors: Alberto Benetti, Marina Del Puppo, Andrea Crosignani, Annamaria Veronelli, Enzo Masci, Francesca Frigè, Giancarlo Micheletto, Valerio Panizzo, Antonio E. Pontiroli
Journal: Diabetes Care (2012)

Malabsorptive bariatric surgery (biliopancreatic diversion and biliointestinal bypass [BIBP]) reduces serum cholesterol levels more than restrictive surgery (adjustable gastric banding [AGB]), and this is thought to be due to greater weight loss. Our aim was to evaluate the changes of cholesterol metabolism induced by malabsorptive and restrictive surgery independent of weight loss.In a nonrandomized, self-selected, unblinded, active-comparator, bicenter, 6-month study, glucose metabolism (blood glucose and serum insulin levels and homeostasis model assessment of insulin resistance [HOMA-IR] index) and cholesterol metabolism (absorption: serum campesterol and sitosterol levels; synthesis: serum lathosterol levels; catabolism: rate of appearance and serum concentrations of serum 7-α- and serum 27-OH-cholesterol after infusions of deuterated 7-α- and 27-OH-cholesterol in sequence) were assessed in grade 3 obesity subjects undergoing BIBP (n = 10) and AGB (n = 10). Evaluations were performed before and 6 months after surgery.Subjects had similar values at baseline. Weight loss was similar in the two groups of subjects, and blood glucose, insulin levels, HOMA-IR, and triglycerides decreased in a similar way. In contrast, serum cholesterol, LDL cholesterol, non-HDL cholesterol, serum sitosterol, and campesterol levels decreased and lathosterol levels increased only in BIBP subjects, not in AGB subjects. A significant increase in 7-α-OH-cholesterol occurred only with BIBP; serum 27-OH-cholesterol decreased in both groups.Malabsorptive surgery specifically affects cholesterol levels, independent of weight loss and independent of glucose metabolism and insulin resistance. Decreased sterol absorption leads to decreased cholesterol and LDL cholesterol levels, accompanied by enhanced cholesterol synthesis and enhanced cholesterol catabolism. Compared with AGB, BIBP provides greater cholesterol lowering.
Antitumor Activities of TEM8-Fc: An Engineered Antibody-like Molecule Targeting Tumor Endothelial Marker 8
Authors: H.-F. Duan, X.-W. Hu, J.-L. Chen, L.-H. Gao, Y.-Y. Xi, Y. Lu, J.-F. Li, S.-R. Zhao, J.-J. Xu, H.-P. Chen, W. Chen, C.-T. Wu
Journal: JNCI Journal of the National Cancer Institute (2007)

Tumor endothelial marker 8 (TEM8) was discovered as a cell membrane protein that is predominantly expressed in tumor endothelium and identified as a receptor for anthrax toxin. We developed an antibody-like molecule that consists of the protective antigen (PA)-binding domain of human TEM8 linked to the Fc portion of human immunoglobulin G1 (TEM8-Fc). This engineered protein bound to PA in a divalent cation-dependent manner and efficiently protected J774A.1 macrophage-like cells against anthrax toxin challenge in a dose-dependent manner. TEM8-Fc suppressed the growth and metastasis of xenograft human tumors in athymic nude mice (control versus 10 mg/kg TEM8-Fc, mean tumor weight: LS-180, 1.72 versus 0.16 g, difference = 1.56 g, 95% confidence interval [CI] = 0.96 to 2.16 g; P<.001; MCF-7, 1.12 versus 0.08 g, difference = 1.04 g, 95% CI = 0.77 to 1.31 g; P<.001; HepG2, 1.28 versus 0.35 g, difference = 0.93 g, 95% CI = 0.60 to 1.25 g; P<.001). Furthermore, TEM8 interacted with the M2 isoenzyme of pyruvate kinase (M2-PK), which has an important role in tumor growth and metastasis. TEM8-Fc is a novel therapeutic antibody-like agent in the management of solid tumors that may act by trapping M2-PK.
Mechanical regulation of cellular phenotype: implications for vascular tissue regeneration
Authors: W. F. Liu
Journal: Cardiovascular Research (2012)

Cells sense a myriad of cues from their surrounding microenvironment to regulate their function. In recent years, it has become clear that physical and mechanical cues are as critical as biochemical factors in regulating cellular function. The geometry of the extracellular matrix (ECM), degree of cell spreading, and ECM rigidity all influence the physical connection between cells and their microenvironment and play a major role in regulating proliferation, differentiation, and migration. Leveraging these findings to promote specific cell behaviours will be paramount to realize the full potential of cellular therapies. In this review, I examine our current understanding of how mechanical cues—specifically, geometric control of cell shape and matrix rigidity—are transduced by stem cells to control their stemness, proliferation, and differentiation. The implications of these findings for vascular smooth muscle cell differentiation and cardiovascular tissue engineering will be highlighted.