tbuckley/cabot-search huggingface dataset:
CONGENITAL DISLOCATION OF THE HIP: LATE RESULTS OF TREATMENT BY MANIPULATION
Authors: E. L. Evans
Journal: BMJ (1930)

I~~~~~~~~~~~~~~~~~*MEDICAL JOux.of thle electric cautery? to the internal os.Three liniear incisions behind anld tlhiree in frolnt are made fromn initerniial to externlal os anid over the catarrhal patch on the vaoginal portioII.The cautery sears thirough the mticosa iiito the subiacent fibro-nmuscuilar wall, arid Nabothian follicles aie individually punctured.In some cases a repetition of the process at the cei(n of a mionith is requiiredl.After each al)l)lication a plain warmi water vagilnal doulche shlould be giveni daily for a week or teii days to act as a miechlaniical cleanser, anid to facilitate the remiioval of the slotughlis whiell sometimes form.
Amelioration of hyperoxia-induced lung injury in newborn mice using a sphingolipid-based intervention
Authors: Jeroen Tibboel, Stephen Joza, Irwin Reiss, Johan C. de Jongste, Martin Post
Journal: European Respiratory Journal (2012)

Aim: To characterize lung function and BAL sphingolipid profile of newborn mice during hyperoxia exposure and recovery in room air, and to examine the effect of D-sphingosine supplementation during recovery.

Methods: Newborn mice were exposed to 80% O2 for 4 weeks and allowed to recover in room air for another 4 weeks. Lung function measurements, histological and morphometrical analysis of lung tissue was performed and BAL fluid was collected during hyperoxia and after recovery with and without D-sphingosine supplementation. Sphingolipids in BAL were quantified by tandem mass spectrometry.

Results: Hyperoxia increased lung resistance and decreased compliance, total lung capacity and forced expiratory flow. After recovery, resistance, compliance and total lung capacity had normalized whereas forced flows remained low. Sphingolipids, including ceramides, were significantly increased after hyperoxia. Ceramides were still increased after 2 weeks of recovery, but normalized to control values after 4 weeks. Addition of D-sphingosine during the first 5 days of recovery reduced ceramide levels at 2 weeks and partially reversed the hyperoxia-induced increase in alveolar size and arrest in alveolarization at 4 weeks, although no further improvement in lung function parameters was observed.

Conclusion: Exposure of newborn mice to hyperoxia caused restrictive and obstructive lung function changes that partially recovered in room air, while alveolar morphology remained abnormal. Hyperoxia increased ceramide levels, with normalization after recovery. D-sphingosine addition during recovery reduced ceramide levels and ameliorated hyperoxia-induced alveolar arrest.
A Structural and Phylogenetic Analysis of the Group IC1 Introns in the Order Bangiales (Rhodophyta)
Authors: Kirsten M. Müller, Jamie J. Cannone, Robin R. Gutell, Robert G. Sheath
Journal: Molecular Biology and Evolution (2001)

Our previous study of the North American biogeography of Bangia revealed the presence of two introns inserted at positions 516 and 1506 in the nuclear-encoded SSU rRNA gene. We subsequently sequenced nuclear SSU rRNA in additional representatives of this genus and the sister genus Porphyra in order to examine the distribution, phylogeny, and structural characteristics of these group I introns. The lengths of these introns varied considerably, ranging from 467 to 997 nt for intron 516 and from 509 to 1,082 nt for intron 1506. The larger introns contained large insertions in the P2 domain of intron 516 and the P1 domain of intron 1506 that correspond to open reading frames (ORFs) with His-Cys box homing endonuclease motifs. These ORFs were found on the complementary strand of the 1506 intron in Porphyra fucicola and P. umbilicalis (HG), unlike the 516 intron in P. abbottae, P. kanakaensis, P. tenera (SK), Bangia fuscopurpurea (Helgoland), and B. fuscopurpurea (MA). Frameshifts were noted in the ORFs of the 516 introns in P. kanakaensis and B. fuscopurpurea (HL), and all ORFs terminated prematurely relative to the amino acid sequence for the homing endonuclease I-Ppo I. This raises the possibility that these sequences are pseudogenes. Phylogenies generated using sequences of both introns and the 18S rRNA gene were congruent, which indicated long-term immobility and vertical inheritance of the introns followed by subsequent loss in more derived lineages. The introns within the florideophyte species Hildenbrandia rubra (position 1506) were included to determine relationships with those in the Bangiales. The two sequences of intron 1506 analyzed in Hildenbrandia were positioned on a well-supported branch associated with members of the Bangiales, indicating possible common ancestry. Structural analysis of the intron sequences revealed a signature structural feature in the P5b domain of intron 516 that is unique to all Bangialean introns in this position and not seen in intron 1506 or other group IC1 introns.
Sensitivity to Fas-Mediated Apoptosis Is Determined Below Receptor Level in Human Vascular Smooth Muscle Cells
Authors: Shiu-Wan Chan, Laszlo Hegyi, Stephen Scott, Nathaniel R. B. Cary, Peter L. Weissberg, Martin R. Bennett
Journal: Circulation Research (2000)

Abstract —Despite Fas expression, many cells resist Fas-induced apoptosis. Although differences in surface Fas expression can explain Fas resistance, multiple proteins below receptor level also inhibit Fas-induced apoptosis. To examine the mechanism of Fas resistance, we studied Fas-induced apoptosis in human medial vascular smooth muscle cells (VSMCs) from healthy coronary arteries. VSMCs showed marked heterogeneity to Fas-induced apoptosis, exhibiting both Fas-resistant (98.1±2.3% viable, n=4, P =NS) and Fas-sensitive (31.3±2.6% viable, n=3, P &lt;0.01) cells. Fas-resistant VSMCs expressed surface Fas and could recruit RIP, indicating that functional receptor complexes were formed. However, Fas-resistant cells showed reduced expression of FADD, Fas ligand, and caspases 3, 7, and 8 and increased expression of FLIP and c-IAP-1. Fas-induced apoptosis was associated with cleavage of caspase 3 and blocked by inhibitors of caspase 3 or 8 but not caspase 1, 6, or 7. Selective inhibition of caspase 3 or 8 by antisense transfection inhibited Fas-induced apoptosis, but their reexpression could not rescue the Fas-resistant phenotype. In vivo, medial VSMCs showed marked heterogeneity of expression of caspase 3. We conclude that Fas sensitivity is determined not only by expression of surface Fas but by differential expression of Fas-signaling proteins below receptor level. Subpopulations of cells within the same tissue have different sensitivities to apoptosis, determined by expression of specific death-signaling proteins.
Congenital Heart Disease
Authors: Benoit G. Bruneau, Deepak Srivastava
Journal: Circulation Research (2014)

Congenital heart disease (CHD) remains a leading cause of morbidity and mortality in childhood and is the most common human birth defect, affecting nearly 1% of all live births worldwide. The morphogenetic events that are disrupted during cardiogenesis that lead to CHD are now partially understood, as are many of the molecular networks that guide normal heart development. Studies of rare Mendelian forms of familial CHD, as well as CHD associated with stereotypic syndromes, have revealed numerous single-gene mutations that cause CHD. However, mutations in these genes are infrequent in the more common sporadic form of CHD. Despite epidemiological evidence for an inherited component in sporadic CHD, the contribution of inherited variants or de novo mutations in the setting of CHD has been unclear. A recent landmark article in Nature begins to tackle this question by using modern genetic approaches and suggests that roughly 10% of sporadic CHD cases have de novo mutations that contribute significantly to the disease process.
Notch2 Activation in the Embryonic Kidney Depletes Nephron Progenitors
Authors: Sayoko Fujimura, Qing Jiang, Chiyoko Kobayashi, Ryuichi Nishinakamura
Journal: Journal of the American Society of Nephrology (2010)

Successive activation of Wnt4 and Notch2 generates nephrons from the metanephric mesenchyme. Mesenchymal-to-epithelial transition requires Wnt4, and normal development of the proximal nephron (epithelia of glomeruli and proximal tubules) requires Notch2. It is unknown, however, whether Notch2 dictates the fate of the proximal nephron directly. Here, we generated a mutant strain of mice with activated Notch2 in Six2-containing nephron progenitor cells of the metanephric mesenchyme. Notch2 activation did not skew the cell fate toward the proximal nephron but resulted in severe kidney dysgenesis and depletion of Six2-positive progenitors. We observed ectopic expression of Wnt4 and premature tubule formation, similar to the phenotype of Six2-deficient mice. Activation of Notch2 in the progenitor cells suppressed Pax2, an upstream regulator of Six2, possibly through Hesr genes. Taken together, these data suggest that a positive feedback loop exists between Notch2 and Wnt4, and that Notch2 stabilizes, rather than dictates, nephron fate by shutting down the maintenance of undifferentiated progenitor cells, thereby depleting this population.
Zidovudine Resistance and HIV-1 Disease Progression during Antiretroviral Therapy
Authors: Richard T. D'Aquila
Journal: Annals of Internal Medicine (1995)

Objective: To evaluate the association between resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine and clinical progression. Design: Retrospective analysis of specimens from patients in the AIDS Clinical Trials Group (ACTG) protocol 116B/117, a randomized comparison of didanosine with continued zidovudine therapy in patients with advanced HIV-1 disease who had received 16 weeks or more of previous zidovudine therapy. Setting: Participating ACTG virology laboratories. Patients: 187 patients with baseline HIV-1 isolates. Measurements: Zidovudine susceptibility testing and assays for syncytium-inducing phenotype were done on baseline HIV-1 isolates. Relative hazards for clinical progression or death associated with baseline clinical, virologic, and immunologic factors were determined from Cox proportional-hazards regression models. Results: Compared with other patients, 15% (26 of 170) with isolates showing high-level zidovudine resistance (50% inhibitory zidovudine concentration ≥ 1.0 µM) had 1.74 times the risk for progressing to a new AIDS-defining event or death (95% CI, 1.00 to 3.03) and 2.78 times the risk for death (CI, 1.21 to 6.39) in analyses that controlled for baseline CD4+ T-lymphocyte count, syncytium-inducing HIV-1 phenotype, disease stage, and randomized treatment assignment. The clinical benefit of didanosine was not limited to patients with highly zidovudine-resistant baseline HIV-1 isolates. Conclusions: High-level resistance of HIV-1 to zidovudine predicted more rapid clinical progression and death when adjusted for other factors. However, patients with advanced HIV-1 disease may benefit from a change in monotherapy from zidovudine to didanosine whether high-level HIV-1 resistance to zidovudine is present or absent, and laboratory assessment of zidovudine resistance is not necessary for deciding when to switch monotherapy from zidovudine to didanosine.
Is leptin associated with diabetic retinopathy?
Authors: G Uckaya, M Ozata, Z Bayraktar, V Erten, N Bingol, I C Ozdemir
Journal: Diabetes Care (2000)

In advanced stages of diabetic retinopathy, new blood vessels are formed based on undefined mechanisms. Recently, leptin was shown to possess an angiogenic action in vitro and to induce neovascularization in vivo. The aim of the present study was to investigate the relationship between plasma leptin levels and the severity of diabetic retinopathy.There were 70 patients with type 2 diabetes (age 47.9 +/- 9.7 years, BMI 26.4 +/- 3.3 kg/m2) who were seen in a retina outpatient clinic recruited and assigned to subgroups according to the stage of their diabetic retinopathy. There were 66 healthy volunteer subjects matched with the diabetic patients for age, BMI, and sex who served as control subjects (age 46.0 +/- 8.8 years, BMI 27.1 +/- 2.3 kg/m2). Fasting plasma leptin levels were measured.Plasma leptin level of the diabetic patients was not significantly different from the control subjects. In patients with proliferative diabetic retinopathy (n = 17), the mean plasma level of leptin (16.1 +/- 9.2 ng/ml) was significantly higher than that in patients with nonproliferative retinopathy (n = 20) (11.5 +/- 3.5 ng/ml, P = 0.039) or patients without retinopathy (n = 33) (5.8 +/- 3.7 ng/ml, P = 0.001). The mean leptin level in patients with nonproliferative diabetic retinopathy was also significantly higher than that in patients without retinopathy (P = 0.002).Our results show that the more advanced the diabetic retinopathy, the higher the plasma leptin levels, even after adjusting the leptin levels for BMI. The presence of such a positive correlation need not imply a causal relationship. Nevertheless, previously observed leptin-induced promotion of angiogenesis and neovascularization lends support to the possibility that leptin may play a role in the progression of human diabetic retinopathy to a proliferative phase. This possibility deserves further investigation.
Searching for hematopoietic stem cells: evidence that Thy-1.1lo Lin- Sca-1+ cells are the only stem cells in C57BL/Ka-Thy-1.1 bone marrow.
Authors: N Uchida, I L Weissman
Journal: The Journal of Experimental Medicine (1992)

Hematopoietic stem cells (HSCs) are defined in mice by three activities: they must rescue lethally irradiated mice (radioprotection), they must self-renew, and they must restore all blood cell lineages permanently. We initially demonstrated that HSCs were contained in a rare (approximately 0.05%) subset of bone marrow cells with the following surface marker profile: Thy-1.1lo Lin- Sca-1+. These cells were capable of long-term, multi-lineage reconstitution and radioprotection of lethally irradiated mice with an enrichment that mirrors their representation in bone marrow, namely, 1,000-2,000-fold. However, the experiments reported did not exclude the possibility that stem cell activity may also reside in populations that are Thy-1.1-, Sca-1-, or Lin+. In this article stem cell activity was determined by measuring: (a) radioprotection provided by sorted cells; (b) long-term, multi-lineage reconstitution of these surviving mice; and (c) long-term, multi-lineage reconstitution by donor cells when radioprotection is provided by coinjection of congenic host bone marrow cells. Here we demonstrate that HSC activity was detected in Thy-1.1+, Sca-1+, and Lin- fractions, but not Thy-1.1-, Sca-1-, or Lin+ bone marrow cells. We conclude that Thy-1.1lo Lin- Sca-1+ cells comprise the only adult C57BL/Ka-Thy-1.1 mouse bone marrow subset that contains pluripotent HSCs.
Clinical and radiographic study of activated carbon workers.
Authors: C G Uragoda
Journal: Thorax (1989)

Activated carbon is made in Sri Lanka by passing steam through charcoal made from coconut shells. The carbon does not contain free silica. Sixty six men who had worked in a factory making activated carbon for an average of 7.2 years had no more respiratory symptoms than a control group, and none showed radiological evidence of pneumoconiosis. There was no evidence that people exposed to charcoal and pure carbon for up to 11 years are at risk of developing pneumoconiosis.
Mixed isotype class II antigen expression. A novel class II molecule is expressed on a murine B cell lymphoma.
Authors: J S Spencer, R T Kubo
Journal: The Journal of Experimental Medicine (1989)

The structures of Ia molecules expressed by two BALB/c B cell lymphoma lines, A20-1.11 (A20) and 2PK3, were analyzed in an effort to explain the differences in antigen-presenting capacity displayed by these cells. Alloreactive T cell hybridomas specific for I-Ad and antigen-specific, I-Ad-restricted T cells responded well to A20 as the APC. The same alloreactive T cell hybridomas responded weakly or not at all to 2PK3 and the responses of the antigen-specific, I-Ad-restricted T cells were consistently lower to antigen presented by 2PK3 as compared with A20. T cells restricted to I-Ed responded equally well to either A20 or 2PK3 as APC. Additionally 2PK3, but not A20, stimulated a strong syngeneic mixed lymphocyte response. Structural analyses of the Ia antigens revealed that I-A and I-E molecules were expressed by A20, whereas an I-E and a novel I-A-like molecule were expressed by 2PK3. The novel class II molecule was affinity purified from 2PK3 cells using an mAb specific for Ad beta (MK-D6), and this molecule was subsequently shown by an RIA to react with an E alpha-specific mAb (14-4-4S) as well. Chain-specific polyclonal antisera raised against I-A and I-E alpha and beta chains indicated that the 2PK3 "I-A" alpha chain reacted in immunoblot with E alpha-specific and not A alpha-specific antisera, whereas the beta chain reacted with A beta- and not E beta-specific antisera. Peptide map and partial amino acid sequence analyses indicated that the "I-A" molecule expressed by 2PK3 represented a mixed isotype structure resulting from the pairing of Ed alpha with Ad beta. By immunofluorescence staining analysis, 2PK3 did not react with an mAb specific for Ad alpha. 2PK3 was capable of limited antigen presentation through the mixed isotype molecule to I-Ad-restricted OVA-specific T cell hybridomas, although the responses induced were low compared with presentation through I-A on A20. Previous descriptions of the expression of mixed isotype class II molecules in the mouse have resulted primarily from DNA-mediated gene transfer experiments. The results presented indicate that a mixed isotype class II molecule can be expressed naturally.
Insulin sensitivity: modulation by nutrients and inflammation
Authors: Simon Schenk, Maziyar Saberi, Jerrold M. Olefsky
Journal: Journal of Clinical Investigation (2008)

Insulin resistance is a major metabolic feature of obesity and is a key factor in the etiology of a number of diseases, including type 2 diabetes. In this review, we discuss potential mechanisms by which brief nutrient excess and obesity lead to insulin resistance and propose that these mechanisms of action are different but interrelated. We discuss how pathways that “sense” nutrients within skeletal muscle are readily able to regulate insulin action. We then discuss how obesity leads to insulin resistance via a complex interplay among systemic fatty acid excess, microhypoxia in adipose tissue, ER stress, and inflammation. In particular, we focus on the hypothesis that the macrophage is an important cell type in the propagation of inflammation and induction of insulin resistance in obesity. Overall, we provide our integrative perspective regarding how nutrients and obesity interact to regulate insulin sensitivity.
The sequential therapy regimen for Helicobacter pylori eradication: a pooled-data analysis
Authors: A. Zullo, V. De Francesco, C. Hassan, S. Morini, D. Vaira
Journal: Gut (2007)

<b>Background::</b> Standard triple therapies are the most used treatment in clinical practice. However, a critical fall in the <i>H pylori</i> eradication rate following these therapies has been observed in the last few years. The sequential regimen is a novel, promising therapeutic approach. <b>Objectives::</b> To evaluate the available data on the sequential therapy regimen. <b>Methods::</b> A pooled-data analysis of all studies on the sequential regimen was performed. The eradication rate was calculated according to gastroduodenal pathology, proton pump inhibitor used, antibiotic resistance, as well as setting (paediatric or geriatric patients). Compliance, side effects, and cost implications were also evaluated. <b>Results::</b> Overall, more than 1800 patients have been treated with the sequential regimen. Such a therapy was superior to 7–10 days triple therapies in paediatric, adult and elderly patients, achieving an eradication rate constantly higher than 90% at ITT analysis. Although primary clarithromycin resistance reduced the efficacy of such a therapy, a success rate significantly higher than that observed with the standard 7–10 days triple therapies was found. <b>Conclusion::</b> The 10-day sequential treatment regimen achieves higher eradication rates than standard triple therapies.
The 2-Nitroimidazole EF5 Is a Biomarker for Oxidoreductases That Activate the Bioreductive Prodrug CEN-209 under Hypoxia
Authors: Jingli Wang, Annika Foehrenbacher, Jiechuang Su, Rita Patel, Michael P. Hay, Kevin O. Hicks, William R. Wilson
Journal: Clinical Cancer Research (2011)

Benzotriazine-N-oxide bioreductive prodrugs such as tirapazamine and its improved analogue CEN-209 (SN30000) have potential for exploiting hypoxia in tumors. Here, we test the hypothesis that the 2-nitroimidazole EF5, in clinical development for both immunohistochemical and positron emission tomography imaging of hypoxia, can detect not only hypoxia but also the one-electron reductases required for activation of these hypoxia-targeted prodrugs.Aerobic and hypoxic covalent binding of [(14)C]-EF5 was determined in human tumor cell lines, including lines with overexpression of NADPH:cytochrome P450 oxidoreductase (CYPOR), and reductive metabolism of tirapazamine and CEN-209 by mass spectrometry. DNA damage response was measured by γH2AX formation. Bioreductive metabolism was modulated in HCT116 tumor xenografts by overexpression of CYPOR and breathing of hyperbaric oxygen or 10% oxygen.Overexpression of CYPOR induced similar 2- to 4-fold increases in EF5 binding and metabolic reduction of tirapazamine and CEN-209 in SiHa and HCT116 cell lines, and similar enhancement of γH2AX formation. EF5 binding and metabolic reduction of the prodrugs were highly correlated in a panel of 14 hypoxic tumor cell lines. In HCT116 xenografts, CYPOR overexpression also significantly increased EF5 binding and CEN-209 reduction, and modification of tumor hypoxia caused similar changes to the bioreductive activation of both agents, resulting in a strong correlation between EF5 binding and CEN209-induced DNA damage (R(2) = 0.68, P < 0.0001) at the individual tumor level.EF5 binding is a promising stratification biomarker for benzotriazine-N-oxide bioreductive prodrugs because of its potential for interrogating reductase activity as well as hypoxia in individual tumors.