tbuckley/cabot-search huggingface dataset:
Lung function changes after allogenic bone marrow transplantation.
Authors: H Link, U Reinhard, M Blaurock, P Ostendorf
Journal: Thorax (1986)

The lung function of 21 patients with leukaemia (11 with acute myeloid leukaemia, six with acute lymphatic leukaemia, four with chronic myeloid leukaemia) and of five with severe aplastic anaemia was tested before and after allogenic bone marrow transplantation. Vital capacity (VC) was lowered in patients with leukaemia before transplantation. VC and FEV1 fell significantly after transplantation. Residual volume (RV) and RV as a percentage of total lung capacity (RV % TLC) were already increased and rose significantly after transplantation. Patients with severe aplastic anaemia had noticeably increased RV and RV % TLC, values that did not change after transplantation. In contrast to the patients with aplastic anaemia, the patients with leukaemia had significantly reduced VC, RV, RV % TLC, and FEV1 before and after transplantation. The specific airway resistance (sRaw) was raised significantly before and after transplantation in the leukaemic patients. In addition, transfer coefficient (Kco) fell significantly more after transplantation in the patients with leukaemia than in those with severe aplastic anaemia. In three patients with histologically established obstructive bronchiolitis in conjunction with chronic graft versus host disease after transplantation, VC, FEV1 and FEV1 % VC fell, while RV, RV % TLC, and sRaw rose; Kco was far below normal. On the basis of these findings it is concluded that in patients with leukaemia obstructive disorders of ventilation develop or, if they are already present, worsen. In patients with severe aplastic anaemia lung function was not impaired in the early phase after transplantation. These differences are probably due to the more intensive immunosuppressive and cytotoxic preparatory regimen before transplantation in the leukaemic patients. Obstructive bronchiolitis, a complication of graft versus host disease, first manifests itself in a typical rise in specific airway resistance and must be treated early.
Insulin resistance and lower plasma adiponectin increase malignancy risk in nondiabetic continuous ambulatory peritoneal dialysis patients
Authors: Jung Tak Park, Tae-Hyun Yoo, Tae Ik Chang, Dong Hyung Lee, Joo Hyun Lee, Jung Eun Lee, Hoon Young Choi, Shin-Wook Kang, Dae-Suk Han, Dong-Ryeol Ryu
Journal: Metabolism (2010)
The Cleaved Cytoplasmic Tail of Polycystin-1 Regulates Src-Dependent STAT3 Activation
Authors: Jeffrey J. Talbot, Xuewen Song, Xiaofang Wang, Markus M. Rinschen, Nicholas Doerr, Wells B. LaRiviere, Bernhard Schermer, York P. Pei, Vicente E. Torres, Thomas Weimbs
Journal: Journal of the American Society of Nephrology (2014)

Polycystin-1 (PC1) mutations result in proliferative renal cyst growth and progression to renal failure in autosomal dominant polycystic kidney disease (ADPKD). The transcription factor STAT3 (signal transducer and activator of transcription 3) was shown to be activated in cyst-lining cells in ADPKD and PKD mouse models and may drive renal cyst growth, but the mechanisms leading to persistent STAT3 activation are unknown. A proteolytic fragment of PC1 corresponding to the cytoplasmic tail, PC1-p30, is overexpressed in ADPKD. Here, we show that PC1-p30 interacts with the nonreceptor tyrosine kinase Src, resulting in Src-dependent activation of STAT3 by tyrosine phosphorylation. The PC1-p30–mediated activation of Src/STAT3 was independent of JAK family kinases and insensitive to the STAT3 inhibitor suppressor of cytokine signaling 3. Signaling by the EGF receptor (EGFR) or cAMP amplified the activation of Src/STAT3 by PC1-p30. Expression of PC1-p30 changed the cellular response to cAMP signaling. In the absence of PC1-p30, cAMP dampened EGFR- or IL-6–dependent activation of STAT3; in the presence of PC1-p30, cAMP amplified Src-dependent activation of STAT3. In the polycystic kidney (PCK) rat model, activation of STAT3 in renal cystic cells depended on vasopressin receptor 2 (V2R) signaling, which increased cAMP levels. Genetic inhibition of vasopressin expression or treatment with a pharmacologic V2R inhibitor strongly suppressed STAT3 activation and reduced renal cyst growth. These results suggest that PC1, via its cleaved cytoplasmic tail, integrates signaling inputs from EGFR and cAMP, resulting in Src-dependent activation of STAT3 and a proliferative response.
Regulation of the Conversion of Thyroxine to Triiodothyronine in the Perfused Rat Liver
Authors: Anthony S. Jennings, Duncan C. Ferguson, Robert D. Utiger
Journal: Journal of Clinical Investigation (1979)

This study was undertaken to determine what factors control the conversion of thyroxine (T4) to triiodothyronine (T3) in rat liver under conditions approximating those found in vivo. Conversion of T4 to T3 was studied in the isolated perfused rat liver, a preparation in which the cellular and structural integrity is maintained and that can perform most of the physiologic functions of the liver. The perfused liver readily extracted T4 from perfusion medium and converted it to T3. Production of T3 by the perfused liver was a function of the size of the liver, the uptake of T4 by the liver, and the presence of T4-5′-deiodinase activity. Production of T3 was increased by increasing the uptake of T4 by liver, which could be accomplished by increasing the liver size, by increasing the perfusate T4 concentration, or by decreasing the perfusate albumin concentration. These changes occurred without altering the conversion of T4 to T3. The liver had a large capacity for extracting T4 and for T4-5′-deiodination to T3, which was not saturated at a T4 concentration of 60 μg/dl. Production of T3 was decreased by inhibiting hepatic T4-5′-deiodinase with propylthiouracil, which decreased T3 production by decreasing the conversion of T4 to T3. Propylthiouracil did not alter hepatic T4 uptake.
Bidirectional effects on autoimmunity and reproduction
Authors: R. Cervera, J. Balasch
Journal: Human Reproduction Update (2008)

Autoimmune diseases may selectively affect women in their reproductive years, and conversely, pregnancy may affect the expression of autoimmune disease. This review addresses the impact of abnormal autoimmunity on female fertility, premature ovarian failure (POF) and recurrent pregnancy loss, as well as the influence of pregnancy in systemic lupus erythematosus (SLE). From a PubMed search, citations were selected for their immunological and gynecological relevance. The presence of antiphospholipid antibody (aPL) does neither correlate with the type of female infertility diagnosis nor affect outcomes, and treatment is not indicated. Autoimmunity as a cause of POF is probably limited to the cases associated with the autoimmune thyroid diseases. With respect to recurrent spontaneous abortion, there is no consensus on the mechanisms of an autoimmune effect, although vasculopathy of the terminal spiral arteries may be implicated, but there is a general consensus to screen for aPL when recurrent spontaneous abortion is unexplained. Well-designed diagnostic studies are needed to estimate the true association between specific autoantibodies and recurrent spontaneous abortion. With respect to SLE, pregnancy should be avoided when the disease is active, and the potentially harmful impact of pregnancy can be minimized by multi-disciplinary care. Autoimmunity may impair female fertility and, in particular, the antiphospholipid syndrome is associated with recurrent spontaneous abortion. Integration of mechanistic and clinical information by multi-disciplinary teams is needed to manage reproductive issues in women with autoimmune diseases.
Emergence of a brain-expressed variant melanin-concentrating hormone gene during higher primate evolution: a gene "in search of a function"
Authors: A. Viale, C. Ortola, F. Richard, P. Vernier, F. Presse, S. Schilling, B. Dutrillaux, J. L. Nahon
Journal: Molecular Biology and Evolution (1998)

Two related but distinct melanin-concentrating hormone (MCH) gene systems, i.e., the authentic and variant genes, have been characterized in the human, while only a single MCH gene has been found in the rat. We previously established that the variant gene corresponds to exon-I-deleted copies of the authentic gene mapped on chromosomes 5 and 12, respectively. In this report, we examined the expression of the authentic and variant MCH genes in the human brain. Mature mRNAs of the authentic MCH gene appeared to be predominantly expressed in the hypothalamus, whereas putative unprocessed transcripts of the variant MCH gene were found in other brain areas but not in the hypothalamus. Several products of the variant MCH gene were identified by RACE-PCR in the fetal human brain. One of these transcripts encoded a putative protein of 72 amino acids, while another transcript may potentially generate a protein of 35 amino acids. Thereafter, we explored the question of MCH gene transposition during Primate evolution. Southern blotting, PCR analyses using several genomic DNAs of Primates, and in situ hybridization on metaphase chromosomes led us to define at least three types of genetic events associated with the emergence of the variant MCH gene: (1) translocation of an exon II-exon III copy of the authentic MCH gene onto the equivalent of the human chromosome 5p arm of Anthropoidea ancestors (between 25 and 55 MYA); (2) exon II truncation and mutations before divergence of the Hylobatidae (about 15 MYA); and (3) duplication of the variant gene on the equivalent of the human chromosome 5p and 5q arms in the Hominidae, i.e., 5-10 MYA. Taken together, these results support the hypothesis that transposition/gene rearrangement processes could underlie the evolutionary emergence of new MCH-related genes expressed differentially in the brains of higher Primates, illustrating the concept of genes "in search of function" instead of true "pseudogenes."
Just how inflamed is the normal gut?
Authors: C O’FARRELLY
Journal: Gut (1998)

See article on page643 

That the science of cartography is limited - and not simply by the fact that this shading of forest cannot show the fragrance of balsam, the gloom of cypresses, is what I wish to prove Eavan Boland 

The mammalian intestine has evolved as a tightly regulated and intricate environment concerned with manipulating vast quantities of complex substances. Ingested matter must be processed, transported and appropriately disposed of without stimulating adverse local reactions while contaminating microorganisms with pathogenic potential must be dispatched. Cytokines are of fundamental importance in all of these processes, yet the pleiotropy, interdependence and redundancy of cytokine networks has made this a difficult and often confusing area to chart.

### NORMAL INTESTINE: A SITE OF CONTROLLED INFLAMMATION

Cytokine studies in the intestine have, in the past, focused on the possible role of these factors as immunological mediators of inflammatory disease states and it has generally been assumed that activation, as a result of some pathogenic process, was required for their secretion. Thus, inflammatory cytokines, including interleukin (IL) 1, IL-2, tumour necrosis factor (TNF) α and interferon (IFN) γ, have all been claimed to be the primary pathogenic mediators in diseases of the intestine such as Crohn’s disease, ulcerative colitis and coeliac disease.1 However, the paper by Lambrechts et al (see page 643) clearly demonstrates that in the absence of stimulation, the healthy intestine contains significant numbers of IL-4 and IFN-γ elaborating intestinal lymphocytes. Using intracytoplasmic staining followed by flow cytometric analysis, this proportion was found to increase dramatically in response to stimulation with almost two thirds of …
Home Energy-Efficiency Retrofits
Authors: Brent Stephens, Ellison M. Carter, Elliott T. Gall, C. Matt Earnest, Elizabeth A. Walsh, Diana E. Hun, Mark C. Jackson
Journal: Environmental Health Perspectives (2011)

A 283 acquiesced to that point in a reply to the first of several letters to the editor by Brondum (2007) on the same topic.However, Braun et al. (2007) noted that including such information is not always possible when, for example, the use of National Health and Nutrition Examination Survey (NHANES) data or other constraints on study design do not allow it.Although we agree that failure to control for parental psycho pathology is a weakness in many of the published studies reporting an association between childhood lead exposure and a diagnosis of ADHD, we believe that the consistency of the association across several published studies using different study designs adds to the weight of evidence that this is a real association and not a spurious effect due to uncontrolled confounding.We hope that this reply clarifies the goals of our review for those faced with the challenge of assessing the neuro behavioral effects of emerging contaminants and their possible contribution to the pheno typic expression of ADHD or other neuro developmental disorders.
Myoelectrical activity of the Billroth II gastric remnant.
Authors: H M Schaap, A J Smout, L M Akkermans
Journal: Gut (1990)

This study was undertaken to investigate the extent to which gastric electrical control activity and phasic contractile activity are preserved after Billroth II resection and to assess the relation between these activities and postprandial symptoms in patients who have undergone Billroth II resection. Thirty three patients were studied after Billroth II resection without vagotomy. Gastric electrical activity was recorded from surface electrodes and intraluminal pressure was recorded simultaneously. The electrogastrographic signals were analysed by Running Spectrum Analysis. In addition, three dogs with a Billroth II stomach and implanted serosal electrodes were studied. Phasic gastric pressure waves were observed in most patients. Electrogastrographic signals recorded from 82% of the Billroth II patients contained a mean (SD) peak at 3.1 (0.2) cycles per minute (cpm). Fasting and postprandial frequencies correlated significantly (p less than 0.02) with the score for nausea and vomiting. In 61% of the patients, the electrogastrographic signal contained a stable component with a frequency of 10.5 (0.6) cpm that was not caused by respiration. We suggest that this activity is of intestinal origin. In all three dogs studied, retrograde conduction of jejunal electrical control activity (16 cpm) into the distal part of the gastric remnant was observed. In the Billroth II patients, the presence of a 10 cpm component correlated negatively with symptoms.
Refined prediction of week 12 response and SVR based on week 4 response in HCV genotype 1 patients treated with peginterferon alfa-2a (40KD) and ribavirin
Authors: Patrick Marcellin, Nancy Reau, Peter Ferenci, Stephanos Hadziyannis, Diethelm Messinger, Fernando Tatsch, Donald Jensen
Journal: Journal of Hepatology (2012)
Targeting atrioventricular differences in ion channel properties for terminating acute atrial fibrillation in pigs
Authors: Sandeep V. Pandit, Sharon Zlochiver, David Filgueiras-Rama, Sergey Mironov, Masatoshi Yamazaki, Steven R. Ennis, Sami F. Noujaim, Antony J. Workman, Omer Berenfeld, Jerome Kalifa, José Jalife
Journal: Cardiovascular Research (2010)

The goal was to terminate atrial fibrillation (AF) by targeting atrioventricular differences in ionic properties.Optical mapping was used to record electrical activity during carbachol (0.25-0.5 μM)-induced AF in pig hearts. The atrial-specific current, I(Kur), was blocked with 100 μM 4-aminopyridine (4-AP) or with 0.5 μM DPO-1. Hearts in AF and ventricular fibrillation (VF) were also subjected to increasing levels of extracellular K(+) ([K(+)](o): 6-12 mM), compared with controls (4 mM). We hypothesized that due to the more negative steady-state half inactivation voltage for the atrial Na(+) current, I(Na), compared with the ventricle, AF would terminate before VF in hyperkalaemia. Mathematical models were used to interpret experimental findings. The I(Kur) block did not terminate AF in a majority of experiments (6/9 with 4-AP and 3/4 with DPO-1). AF terminated in mild hyperkalaemia ([K(+)](o) ≤ 10.0 mM; N = 8). In contrast, only two of five VF episodes terminated at the maximum ([K(+)](o): 12 mM [K(+)](o)). The I(Kur) block did not terminate a simulated rotor in cholinergic AF because its contribution to repolarization was dwarfed by the large magnitude of the acetylcholine-activated K(+) current (I(K,ACh)). Simulations showed that the lower availability of the atrial Na(+) current at depolarized potentials, and a smaller atrial tissue size compared with the ventricle, could partly explain the earlier termination of AF compared with VF during hyperkalaemia.I(Kur) is an ineffective anti-arrhythmic drug target in cholinergic AF. Manipulating Na(+) current 'availability' might represent a viable anti-arrhythmic strategy in AF.
Bedside Ultrasound Assessment of Positive End-Expiratory Pressure–induced Lung Recruitment
Authors: Belaïd Bouhemad, Hélène Brisson, Morgan Le-Guen, Charlotte Arbelot, Qin Lu, Jean-Jacques Rouby
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

In the critically ill patients, lung ultrasound (LUS) is increasingly being used at the bedside for assessing alveolar-interstitial syndrome, lung consolidation, pneumonia, pneumothorax, and pleural effusion. It could be an easily repeatable noninvasive tool for assessing lung recruitment.Our goal was to compare the pressure-volume (PV) curve method with LUS for assessing positive end-expiratory pressure (PEEP)-induced lung recruitment in patients with acute respiratory distress syndrome/acute lung injury (ARDS/ALI).Thirty patients with ARDS and 10 patients with ALI were prospectively studied. PV curves and LUS were performed in PEEP 0 and PEEP 15 cm H₂O₂. PEEP-induced lung recruitment was measured using the PV curve method.Four LUS entities were defined: consolidation; multiple, irregularly spaced B lines; multiple coalescent B lines; and normal aeration. For each of the 12 lung regions examined, PEEP-induced ultrasound changes were measured, and an ultrasound reaeration score was calculated. A highly significant correlation was found between PEEP-induced lung recruitment measured by PV curves and ultrasound reaeration score (Rho = 0.88; P < 0.0001). An ultrasound reaeration score of +8 or higher was associated with a PEEP-induced lung recruitment greater than 600 ml. An ultrasound lung reaeration score of +4 or less was associated with a PEEP-induced lung recruitment ranging from 75 to 450 ml. A statistically significant correlation was found between LUS reaeration score and PEEP-induced increase in Pa(O₂) (Rho = 0.63; P < 0.05).PEEP-induced lung recruitment can be adequately estimated with bedside LUS. Because LUS cannot assess PEEP-induced lung hyperinflation, it should not be the sole method for PEEP titration.
The Plasmodium Apicoplast Genome: Conserved Structure and Close Relationship of P. ovale to Rodent Malaria Parasites
Authors: N. Arisue, T. Hashimoto, H. Mitsui, N. M. Q. Palacpac, A. Kaneko, S. Kawai, M. Hasegawa, K. Tanabe, T. Horii
Journal: Molecular Biology and Evolution (2012)

Apicoplast, a nonphotosynthetic plastid derived from secondary symbiotic origin, is essential for the survival of malaria parasites of the genus Plasmodium. Elucidation of the evolution of the apicoplast genome in Plasmodium species is important to better understand the functions of the organelle. However, the complete apicoplast genome is available for only the most virulent human malaria parasite, Plasmodium falciparum. Here, we obtained the near-complete apicoplast genome sequences from eight Plasmodium species that infect a wide variety of vertebrate hosts and performed structural and phylogenetic analyses. We found that gene repertoire, gene arrangement, and other structural attributes were highly conserved. Phylogenetic reconstruction using 30 protein-coding genes of the apicoplast genome inferred, for the first time, a close relationship between P. ovale and rodent parasites. This close relatedness was robustly supported using multiple evolutionary assumptions and models. The finding suggests that an ancestral host switch occurred between rodent and human Plasmodium parasites.
Captopril prevents nephropathy in HIV-transgenic mice.
Authors: J E Bird, S K Durham, M R Giancarli, P H Gitlitz, D G Pandya, D M Dambach, M M Mozes, J B Kopp
Journal: Journal of the American Society of Nephrology (1998)

Transgenic mice (T26) bearing the envelope, regulatory, and accessory genes of HIV- I develop renal disease resembling human HIV-associated nephropathy (HIVAN). Effects of vehicle (VEH) and the angiotensin-converting enzyme inhibitor captopril (CAP) were examined in wild-type (WT) or T26 mice treated from 7 to 100 d of age. Mortality was lower in CAP T26 mice (30 mg/kg: 8%; 100 mg/kg: 12%) than VEH T26 mice (52%). The urinary protein/creatinine ratio was increased in VEH T26 mice (19.5+/-7.60) versus WT mice (6.1+/-0.83), but not in low-dose (7.3+/-0.94) or high-dose (8.2+/-1.02) CAP T26 mice. Blood urea nitrogen was higher in VEH T26 mice (52+/-16.2 mg/dl) than VEH WT mice (24+/-0.8). Blood urea nitrogen was also elevated in CAP WT (high dose: 43+/-2.1 mg/dl) and T26 mice (high dose: 42+/-2.4 mg/dl). Glomerular injury was higher in VEH T26 mice (6.8+/-0.58) than VEH WT mice (0.2+/-0.08) or CAP T26 mice (low dose: 1.1+/-0.17; high dose: 0.7+/-0.13). Tubulointerstitial injury was also greater in VEH T26 mice (1.1+/-0.10) than VEH WT mice (0.2+/-0.08) or CAP T26 mice (low dose: 0.4+/-0.10; high dose: 0.3+/-0.10). These data validate recent nonrandomized studies of captopril in HIV-infected patients, and suggest that an angiotensin-converting enzyme substrate is an important mediator in HIVAN. A randomized placebo-controlled trial of captopril in HIVAN may be warranted.
THE MOLECULAR WEIGHT OF ANTIBODIES
Authors: Elvin A. Kabat
Journal: The Journal of Experimental Medicine (1939)

1. Highly purified preparations of homogeneous antibody can be made by the salt dissociation methods (6, 7) without any change in sedimentation due to the method of purification. 2. Antibodies prepared from sera of various animal species fall into two groups as regards molecular weight; in one group cow, horse, and pig, a heavy molecule of molecular weight 990,000 is formed; in human being, rabbit, and monkey, the molecular size is that of the normal gamma serum globulin. Both types of antibody molecules are either not compact or not spherical since the frictional ratios f/f(0) are 2.0 and 1.5 respectively. 3. Horse antibody shows an unchanged activity and sedimentation diagram between pH 3.44-9.06, although there is some aggregation at the more acid and some dissociation at the more alkaline pH. At pH 1.44 the antibody activity is unchanged but some breakdown of the molecule takes place. At pH 12.4 activity is destroyed and the molecule is completely broken down. 4. Some horse antibody preparations show evidence of breakdown of the antibody into inhomogeneous material on continued immunization over a long period.
Are forward models enough to explain self-monitoring? Insights from patients and eye movements
Authors: Robert J. Hartsuiker
Journal: Behavioral and Brain Sciences (2013)

Abstract At the core of Pickering &amp; Garrod's (P&amp;G's) theory is a monitor that uses forward models. I argue that this account is challenged by neuropsychological findings and visual world eye-tracking data and that it has two conceptual problems. I propose that conflict monitoring avoids these issues and should be considered a promising alternative to perceptual loop and forward modeling theories.