tbuckley/cabot-search huggingface dataset:
Reduced Wall Compliance Suppresses Akt-Dependent Apoptosis Protection Stimulated by Pulse Perfusion
Authors: Manxiang Li, Kuan-Rau Chiou, Artem Bugayenko, Kaikobad Irani, David A. Kass
Journal: Circulation Research (2005)

Reduced arterial compliance and increased pulse pressure are common and major risk factors for cardiovascular disease. Here, we reveal a novel mechanism whereby loss of wall distensibility blunts endothelial cell protection to oxidant stress-induced apoptosis. Bovine aortic endothelial cells cultured in compliant or stiff silastic tubes were pulse perfused by arterial pressure/flow waveforms generated by a servo-pump. Pulse perfusion induced time-dependent Akt activation peaking >6-fold after 2 hours in compliant tubes and a similar time course but half the magnitude in stiff tubes. This was accompanied by quantitatively similar disparities in phosphoinositide-3 kinase activation and in Akt-stimulated suppressors of apoptosis: glycogen synthase kinase-3beta, forkhead, and Bad. Cells perfused in compliant tubes had twice the protection against H2O2-stimulated apoptosis than those in stiffer tubes. This protection was lost by pretreatment with an Akt inhibitor and restored in cells transfected with myristoylated Akt yet perfused in stiff tubes. Shear and stretch Akt signaling coupled to different upstream pathways as inhibition of vascular endothelial growth factor receptor 2 (VEGF2R) or disruption of caveolae blocked steady and pulse flow-mediated activation, yet did not suppress phosphorylated Akt induced by pulse perfusion in compliant tubes (concomitant stretch). Unlike Akt, reactive oxygen species, activated nuclear factor kappaB, and suppression of H2O2-stimulated c-Jun-N-terminal kinase activity were similar in pulse-perfused compliant and stiff tubes. Thus, cyclic endothelial cell stretch by pulse perfusion enhances Akt-dependent antiapoptosis above that induced by steady or phasic shear stress and, unlike the latter, signals via a VEGF2R/caveolae-independent pathway. Enhancing this stretch pathway may prove useful for improving endothelial function in stiff arteries.
Thrombosis of Inferior Vena Cava
Authors: T. F. H. Smith
Journal: BMJ (1893)

THROMBOSIS OF INFERIOR CAVA.[ ,THDBRITISOUAL 9 was noticed for the first time in the winter of 1888-89.THROMBOSIS OF INFERIOR VENA CAVA.-`F or the past two years the man has been actively engaged BY "T.F
The role of environmental and occupational exposures in Turkish immigrants with fibre-related disease
Authors: P. Dumortier, A. Göcmen, K. Laurent, A. Manço, P. De Vuyst
Journal: European Respiratory Journal (2001)

Environmental exposure to tremolite and erionite causes endemic diseases of the lung and pleura in Turkey. This study aimed to evaluate the impact of these exposures and further occupational exposures on fibre-related diseases in Turkish immigrants living in Belgium. The study included 51 males and 17 females that emigrated &lt;1–38 yrs ago. Most of them (n=46) had nonmalignant pleural lesions, one had asbestosis and one had mesothelioma. Environmental asbestos exposure was likely for the majority of patients (60%), but there were also reports of possible occupational asbestos (n=14) and erionite (n=2) exposure. Tremolite was the main fibre type in bronchoalveolar lavage fluid (BALF). Elevated concentrations of amosite or crocidolite were detected in only two patients. The delay elapsed since the end of the environmental exposure had no influence on the asbestos body or the tremolite fibre concentrations in the BALF of Turkish immigrants. Most fibre-related diseases in Turkish immigrants are probably due to environmental rather than occupational exposure. Precise information about geographical origin and occupation should be obtained when investigating these patients. Mineralogical analysis of bronchoalveolar lavage fluid gives valuable information on the type and intensity of exposure, especially in patients with both environmental and occupational exposure.
MicroRNA-124 inhibits the progression of adjuvant-induced arthritis in rats
Authors: Yuji Nakamachi, Kenichiro Ohnuma, Kenichi Uto, Yoriko Noguchi, Jun Saegusa, Seiji Kawano
Journal: Annals of the Rheumatic Diseases (2015)

Objective MicroRNAs (miRNAs) are small endogenous, non-coding RNAs that act as post-transcriptional regulators. We analysed the in vivo effect of miRNA-124 (miR-124, the rat analogue of human miR-124a) on adjuvant-induced arthritis (AIA) in rats. Methods AIA was induced in Lewis rats by injecting incomplete Freund's adjuvant with heat-killed Mycobacterium tuberculosis . Precursor (pre)-miR-124 was injected into the right hind ankle on day 9. Morphological changes in the ankle joint were assessed by micro-CT and histopathology. Cytokine expression was examined by western blotting and real-time RT-PCR. The effect of miR-124 on predicted target messenger RNAs (mRNAs) was examined by luciferase reporter assays. The effect of pre-miR-124 or pre-miR-124a on the differentiation of human osteoclasts was examined by tartrate-resistant acid phosphatase staining. Results We found that miR-124 suppressed AIA in rats, as demonstrated by decreased synoviocyte proliferation, leucocyte infiltration and cartilage or bone destruction. Osteoclast counts and expression level of receptor activator of the nuclear factor κB ligand (RANKL), integrin β1 (ITGB1) and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) were reduced in AIA rats treated with pre-miR-124. Luciferase analysis showed that miR-124 directly targeted the 3′UTR of the rat NFATc1, ITGB1, specificity protein 1 and CCAAT/enhancer-binding protein α mRNAs. Pre-miR-124 also suppressed NFATc1 expression in RAW264.7 cells. Both miR-124 and miR-124a directly targeted the 3′-UTR of human NFATc1 mRNA, and both pre-miR-124 and pre-miR-124a suppressed the differentiation of human osteoclasts. Conclusions We found that miR-124 ameliorated AIA by suppressing critical prerequisites for arthritis development, such as RANKL and NFATc1. Thus, miR-124a is a candidate for therapeutic use for human rheumatoid arthritis.
Role of Limited Sublobar Resection for Early-Stage Lung Cancer: Steady Progress
Authors: Hisao Asamura
Journal: Journal of Clinical Oncology (2014)

The operative modes for pulmonary parenchymal resection include pneumonectomy, bilobectomy, lobectomy, segmentectomy, and wedge resection, according to the volume of lung parenchyma to be resected. From a technical viewpoint, with respect to the pulmonaryhilum,thesecanbedividedintononanatomic(wedgeresection) and anatomic (all other) resections. The characteristic feature of anatomic resections is that the parenchymal extent of resection is automatically determined according to the bronchovascular anatomy of the lung. For segmentectomy and wedge resection, the term sublobar resection is sometimes used. However, although sublobar resection is used to describe both approaches, both the segmental bronchus and pulmonaryarteryaredividedatthehiluminsegmentectomy,whereas in wedge resection, the extent of resection is arbitrarily determined in relation to the location of the target lesion, and the hilum remains intact. The term limited resection is also used as opposed to the term standard resection, which is essentially at least lobectomy with hilar and mediastinal lymph node sampling/dissection. Therefore, the present-day limited resection inevitably indicates sublobar resection. In the 1930s, Churchill and Belsey 1 introduced segmentectomy
Estrogen receptor alpha deletion enhances the metastatic phenotype of Ron overexpressing mammary tumors in mice
Authors: Aaron M Marshall, Rebecca J McClaine, Devikala Gurusamy, Jerilyn K Gray, Kara E Lewnard, Sohaib A Khan, Susan E Waltz
Journal: Molecular Cancer (2012)

Abstract Background The receptor tyrosine kinase family includes many transmembrane proteins with diverse physiological and pathophysiological functions. The involvement of tyrosine kinase signaling in promoting a more aggressive tumor phenotype within the context of chemotherapeutic evasion is gaining recognition. The Ron receptor is a tyrosine kinase receptor that has been implicated in the progression of breast cancer and evasion of tamoxifen therapy. Results Here, we report that Ron expression is correlated with in situ , estrogen receptor alpha (ERα)-positive tumors, and is higher in breast tumors following neoadjuvant tamoxifen therapy. We also demonstrate that the majority of mammary tumors isolated from transgenic mice with mammary specific-Ron overexpression (MMTV-Ron mice), exhibit appreciable ER expression. Moreover, genetic-ablation of ERα, in the context of Ron overexpression, leads to delayed mammary tumor initiation and growth, but also results in an increased metastasis. Conclusions Ron receptor overexpression is associated with ERα-positive human and murine breast tumors. In addition, loss of ERα on a Ron overexpressing background in mice leads to the development of breast tumors which grow slower but which exhibit more metastasis and suggests that targeting of ERα, as in the case of tamoxifen therapy, may reduce the growth of Ron overexpressing breast cancers but may cause these tumors to be more metastatic.
Effect of the Integrated Management of Childhood Illness strategy on childhood mortality and nutrition in a rural area in Bangladesh: a cluster randomised trial
Authors: Shams E Arifeen, DM Emdadul Hoque, Tasnima Akter, Muntasirur Rahman, Mohammad Enamul Hoque, Khadija Begum, Enayet K Chowdhury, Rasheda Khan, Lauren S Blum, Shakil Ahmed, M Altaf Hossain, Ashraf Siddik, Nazma Begum, Qazi Sadeq-ur Rahman, Twaha M Haque, Sk Masum Billah, Mainul Islam, Reza Ali Rumi, Erin Law, ZA Motin Al-Helal, Abdullah H Baqui, Joanna Schellenberg, Taghreed Adam, Lawrence H Moulton, Jean-Pierre Habicht, Robert W Scherpbier, Cesar G Victora, Jennifer Bryce, Robert E Black
Journal: The Lancet (2009)
PUMA is critical for neonatal cardiomyocyte apoptosis induced by endoplasmic reticulum stress
Authors: P NICKSON, A TOTH, P ERHARDT
Journal: Cardiovascular Research (2006)

Objective: Puma (p53-upregulated modulator of apoptosis), a proapoptotic BH3-only member of the Bcl-2 protein family, has been implicated in the pathomechanism of several diseases, including cancer, AIDS, and ischemic brain disease. We have recently shown that Puma is required for cardiac cell death upon ischemia/reperfusion of mouse hearts. Since ischemia/reperfusion is also associated with endoplasmic reticulum (ER) stress, in the present study we investigated whether Puma contributes to the ER stress-dependent component of cardiomyocyte apoptosis.
Contribution of Stent Underexpansion to Recurrence After Sirolimus-Eluting Stent Implantation for In-Stent Restenosis
Authors: Kenichi Fujii, Gary S. Mintz, Yoshio Kobayashi, Stéphane G. Carlier, Hideo Takebayashi, Takenori Yasuda, Issam Moussa, George Dangas, Roxana Mehran, Alexandra J. Lansky, Arlene Reyes, Edward Kreps, Michael Collins, Antonio Colombo, Gregg W. Stone, Paul S. Teirstein, Martin B. Leon, Jeffrey W. Moses
Journal: Circulation (2004)

Background— We used intravascular ultrasound (IVUS) to evaluate recurrence after sirolimus-eluting stent (SES) implantation treatment of in-stent restenosis (ISR). Methods and Results— Forty-eight ISR lesions (41 patients with objective evidence of ischemia) were treated with SES. Recurrent ISR was identified in 11 lesions (all focal); repeat revascularization was performed in 10. These were compared with 16 patients (19 lesions) without recurrence as documented by angiography. Nine of 11 recurrent lesions had a minimum stent area (MSA) &lt;5.0 mm 2 versus 5 of 19 nonrecurrent lesions ( P =0.003); 7 of 11 recurrent lesions had an MSA &lt;4.0 mm 2 versus 4 of 19 nonrecurrent lesions ( P =0.02); and 4 of 11 recurrent lesions had an MSA &lt;3.0 mm 2 versus 1 of 19 nonrecurrent lesions ( P =0.03). A gap between SESs was identified in 3 of 11 recurrences versus 1 of 19 nonrecurrent lesions. Conclusions— Stent underexpansion is a significant cause of failure after SES implantation treatment of ISR.
Granulomatous Pneumocystis carinii pneumonia in Wegener′s granulomatosis
Authors: E. Ullmer, M. Mayr, I Binet, C Ebnöther-Staub, P Dalquen, M Solèr, M Tamm
Journal: European Respiratory Journal (2000)

This study reports on a first case of granulomatous Pneumocystis carinii pneumonia (PCP) in a human immunodeficiency virus-negative patient with antineutrophil cytoplasmic antibody-positive Wegener's granulomatosis whilst receiving immunosuppressive treatment. The patient presented with diffuse alveolar haemorrhage, pauci-immune rapid progressive glomerulonephritis and leukocytoclastic vasculitis of the skin. Granulomatous Pneumocystis carinii pneumonia developed under immunosuppressive treatment with cyclophosphamide and prednisone. At the time Pneumocystis carinii pneumonia developed, there was a marked lymphopenia with a very low CD8+ cell count in the blood. Grocott staining in bronchoalveolar lavage fluid revealed no Pneumocystis carinii. The diagnosis was made via a video-assisted thoracoscopic lung biopsy which showed granulomas containing high numbers of Pneumocystis carinii cysts.
Hereditary defect of intestinal iron transport in mice with sex-linked anemia
Authors: John A. Edwards, Robin M. Bannerman
Journal: Journal of Clinical Investigation (1970)

Iron transport by everted duodenal sacs in vitro was studied in mice with sex-linked anemia (gene symbol sla) (an inherited iron deficiency anemia), in normal mice, and in normal mice on iron-deficient and iron supplemented diets. Although the over-all mucosal uptake of iron was the same in sla and normal sacs, transport of iron to the inside of the sac was much decreased in sla. The iron transport defect in sla was emphasized by the fact that genotypically normal mice on an iron-deficient diet demonstrated greatly increased iron transport. Electrophoretic analysis of protein extracted from sla and normal sacs showed only one iron-binding fraction. The sla and normal fractions had the same mobility and corresponded in position to the major band of horse ferritin. It thus appears that the iron deficiency of sla is due to a genetically determined defect in mucosal iron transport and that this defect is not associated with any demonstrable abnormality of a major iron-binding protein.
Ocular Manifestations of Trichothiodystrophy
Authors: Brian P. Brooks, Amy H. Thompson, Janine A. Clayton, Chi-Chao Chan, Deborah Tamura, Wadih M. Zein, Delphine Blain, Casey Hadsall, John Rowan, Kristen E. Bowles, Sikandar G. Khan, Takahiro Ueda, Jennifer Boyle, Kyu-Seon Oh, John J. DiGiovanna, Kenneth H. Kraemer
Journal: Ophthalmology (2011)
Liver disease progression and virological response: entecavir rescue still possible in the setting of rtM204I lamivudine-resistant mutation
Authors: Poh Seng Tan, Myat Oo Aung, Yock Young Dan, Yin Mei Lee, Kieron Lim, How Cheng Low, Guan Huei Lee, Maung Aye Thwin, Charlene Soon, Seng Gee Lim
Journal: Gut (2012)

We read with interest the paper by Zoutendijk et al who found that entecavir-induced virological response (VR) reduces the probability of liver disease progression (LDP) in chronic hepatitis B (CHB) patients with cirrhosis. They also found previous lamivudine treatment not to be a significant risk factor,1 but as a large number of lamivudine-experienced CHB patients exist, the impact of different types of lamivudine exposure on entecavir resistance in entecavir-treated real-world patients is not well documented, and can lead to suboptimal VR, virological breakthrough and entecavir resistance. We report here our long-term study, from 2005 to 2011, of 300 real-world entecavir-treated CHB patients, including 90 (30%) nucleos(t)ide-experienced cases. The baseline demographics are shown in table 1. Mean duration of entecavir therapy and follow-up was 30.5 (95% CI 28.6 to 32.4) and 32.7 (95% CI 30.8 to 34.6) months, respectively.

View this table:

Table 1 
Baseline demographics of the entecavir-treatment cohort (n=300)



The cumulative probability of entecavir-induced VR was 96.5% by year 4. Similar to Zoutendijk's study, baseline liver disease severity did not influence VR rates in our cohort (p=0.72). Using Cox regression correcting for baseline factors, like lamivudine exposure and cirrhosis, only HBeAg-negative status (HR=2.07; 95% CI 1.56 to 2.75; p<0.001) and lower Hepatitis B …
Basal Insulin Therapy in Type 2 Diabetes
Authors: Julio Rosenstock, Sherwyn L. Schwartz, Charles M. Clark, Glen D. Park, David W. Donley, Mike B. Edwards
Journal: Diabetes Care (2001)

OBJECTIVE—To determine the safety and efficacy of the long-acting analog insulin glargine compared with NPH insulin in patients with type 2 diabetes who were previously treated with insulin alone. RESEARCH DESIGN AND METHODS—A total of 518 subjects with type 2 diabetes who were receiving NPH insulin with or without regular insulin for postprandial control were randomized to receive insulin glargine (HOE 901) once daily (n = 259) or NPH insulin once or twice daily (n = 259) for 28 weeks in an open-label, multicenter trial. Doses were adjusted to obtain target fasting glucose &amp;lt;6.7 mmol/l. At study end point, the median total daily insulin dose in both treatment groups was 0.75 IU/kg. RESULTS—The treatment groups showed similar improvements in HbA1c from baseline to end point on intent-to-treat analysis. The mean change (means ± SD) in HbA1c from baseline to end point was similar in the insulin glargine group (−0.41 ± 0.1%) and the NPH group (−0.59 ± 0.1%) after patients began with an average baseline HbA1c of ∼8.5%. The treatments were associated with similar reductions in fasting glucose levels. Overall, mild symptomatic hypoglycemia was similar in insulin glargine subjects (61.4%) and NPH insulin subjects (66.8%). However, nocturnal hypoglycemia in the insulin glargine group was reduced by 25% during the treatment period after the dose-titration phase (26.5 vs. 35.5%, P = 0.0136). Subjects in the insulin glargine group experienced less weight gain than those in the NPH group (0.4 vs. 1.4 kg, P &amp;lt; 0.0007). CONCLUSIONS—In patients with type 2 diabetes, once-daily bedtime insulin glargine is as effective as once- or twice-daily NPH in improving and maintaining glycemic control. In addition, insulin glargine demonstrates a lower risk of nocturnal hypoglycemia and less weight gain compared with NPH insulin.
Outcomes after Lung Retransplantation in the Modern Era
Authors: Steven M. Kawut, David J. Lederer, Shaf Keshavjee, Jessie S. Wilt, Theresa Daly, Frank D'Ovidio, Joshua R. Sonett, Selim M. Arcasoy, Mark L. Barr
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Characteristics of and survival estimates for recipients of lung retransplantation in the modern era are unknown.To compare lung retransplant patients in the modern era with historical retransplant patients, to compare retransplant patients with initial transplant patients in the modern era, and to determine the predictors of the risk of death after lung retransplantation.We performed a retrospective cohort study of patients who underwent lung retransplantation between January 2001 and May 2006 in the United States (modern retransplant cohort). The characteristics and survival of this cohort were compared with those of patients who underwent first lung retransplantation between January 1990 and December 2000 (historical retransplant cohort) and patients who underwent initial lung transplantation between January 2001 and May 2006 (modern initial transplant cohort).Modern retransplant recipients (n = 205) had a lower risk of death compared with that of the historical retransplant cohort (n = 184) (hazard ratio, 0.7; 95% confidence interval, 0.5-0.9; P = 0.006). However, modern retransplant recipients had a higher risk of death than that of patients who underwent initial lung transplantation (n = 5,657) (hazard ratio, 1.3; 95% confidence interval, 1.2-1.5; P = 0.001), which appeared to be explained by a higher prevalence of certain comorbidities. Retransplantation at less than 30 days after the initial transplant procedure was associated with worse survival.Outcomes after lung retransplantation have improved; however, retransplantation continues to pose an increased risk of death compared with the initial transplant procedure. Retransplantation early after the initial transplant poses a particularly high mortality risk.
Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell–mediated liver damage
Authors: Claire Dunn, Maurizia Brunetto, Gary Reynolds, Theodoros Christophides, Patrick T. Kennedy, Pietro Lampertico, Abhishek Das, A. Ross Lopes, Persephone Borrow, Kevin Williams, Elizabeth Humphreys, Simon Afford, David H. Adams, Antonio Bertoletti, Mala K. Maini
Journal: The Journal of Experimental Medicine (2007)

Hepatitis B virus (HBV) causes chronic infection in more than 350 million people worldwide. It replicates in hepatocytes but is non-cytopathic; liver damage is thought to be immune mediated. Here, we investigated the role of innate immune responses in mediating liver damage in patients with chronic HBV infection. Longitudinal analysis revealed a temporal correlation between flares of liver inflammation and fluctuations in interleukin (IL)-8, interferon (IFN)-α, and natural killer (NK) cell expression of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) directly ex vivo. A cross-sectional study confirmed these findings in patients with HBV-related liver inflammation compared with healthy carriers. Activated, TRAIL-expressing NK cells were further enriched in the liver of patients with chronic HBV infection, while their hepatocytes expressed increased levels of a TRAIL death–inducing receptor. IFN-α concentrations found in patients were capable of activating NK cells to induce TRAIL-mediated hepatocyte apoptosis in vitro. The pathogenic potential of this pathway could be further enhanced by the ability of the IFN-α/IL-8 combination to dysregulate the balance of death-inducing and regulatory TRAIL receptors expressed on hepatocytes. We conclude that NK cells may contribute to liver inflammation by TRAIL-mediated death of hepatocytes and demonstrate that this non-antigen–specific mechanism can be switched on by cytokines produced during active HBV infection.
Amplification and sequence analysis of partial bacterial 16S ribosomal RNA gene in gallbladder bile from patients with primary biliary cirrhosis
Authors: Katsushi Hiramatsu, Kenichi Harada, Koichi Tsuneyama, Motoko Sasaki, Shinichi Fujita, Takuma Hashimoto, Shuichi Kaneko, Kenichi Kobayashi, Yasuni Nakanuma
Journal: Journal of Hepatology (2000)
Cross-Talk Between Human Mast Cells and Bronchial Epithelial Cells In The Production Of Plasminogen Activator Inhibitor-1 Via TGF-β1
Authors: Seong Ho Cho, Sun Hye Lee, Atsushi Kato, Tetsuji Takabayashi, Soon Shin, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2014)
Hypoxia Signaling—License to Metastasize
Authors: Sakari Vanharanta, Joan Massagué
Journal: Cancer Discovery (2013)

Abstract Summary: Hypoxia-inducible factors (HIF) have long been linked to malignant tumor phenotypes in various cancer types, and several downstream mediators of HIF action are deregulated in metastatic carcinomas. A new study links hypoxia-induced collagen remodeling to sarcoma progression, providing evidence for unifying mechanisms of carcinoma and sarcoma metastasis. Cancer Discov; 3(10); 1103–4. ©2013 AACR. See related article by Eisinger-Mathason et al., p. 1190