tbuckley/cabot-search huggingface dataset:
The Transforming Growth Factor-β Family Members Bone Morphogenetic Protein-2 and Macrophage Inhibitory Cytokine-1 as Mediators of the Antiangiogenic Activity of <i>N</i>-(4-Hydroxyphenyl)Retinamide
Authors: Nicoletta Ferrari, Ulrich Pfeffer, Raffaella Dell'Eva, Claudia Ambrosini, Douglas M. Noonan, Adriana Albini
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Tumor growth appears to be an angiogenesis-dependent process. N-(4-hydroxyphenyl)retinamide (fenretinide; 4HPR) has been found to inhibit and/or prevent tumor growth under diverse conditions. Although 4HPR is antiangiogenic, the molecular mechanisms of this effect remain largely unknown. Experimental Design: Endothelial cells were treated with 4HPR in vitro to study the effects on migration, invasion, and organization, as well as gene expression by microarray and quantitative PCR studies. In vivo angiogenesis was evaluated in the Matrigel model. Results: 4HPR treatment substantially modified the biological activities of endothelial cells, repressing their capacity to migrate, invade, and organize into capillary-like structures. The inhibition of invasion induced by 4HPR was also associated with decreased activities of the metalloproteases matrix metalloproteinase-2 and CD13/APN. Using oligonucleotide microarrays, we observed that bone morphogenetic protein-2 and macrophage inhibitory cytokine-1, two multifunctional cytokines of the transforming growth factor-β family that regulate the growth, differentiation, apoptosis, and matrix accumulation of a variety of cells, are up-regulated in vitro by 4HPR. Both these molecules specifically inhibited endothelial cell growth, migration, and invasion in vitro and suppressed angiogenesis in the Matrigel plug assay in vivo. Blocking antibodies to bone morphogenetic protein-2 were able to reverse the suppressive effects of 4HPR in vitro and in vivo. Conclusions: These data support the conclusion that 4HPR inhibits tumor growth by repression of new vessel growth and identify novel points of regulation of angiogenesis in transforming growth factor-β family proteins.
Viability of autologous fascia lata in heart valve replacements
Authors: J. C. R. Lincoln, P. A. Riley, A. Revignas, M. Geens, D. N. Ross, J. K. Ross
Journal: Thorax (1971)

A histological and radioautographic examination of 11 autologous fascia lata heart valves used in man is described. There was a significant decrease, exponential with time, in the number of fibroblasts per unit volume (P&lt;0·001). The collagen bundles were grossly disorganized and separated, suggesting a breakdown of the cross-linkage in the tissue. Redundant connective tissue on the surface of the valve cusp became oedematous and contained many trapped cells. A pseudoendothelium was formed within 10 days. Incorporation of tritium-labelled thymidine in the nuclei of the fibroblasts showed a sixfold reduction over 9 to 12 weeks following implantation, suggesting a failure of metabolism in these cells. The suitability of fascia lata for human heart valve replacement is discussed.
Imbalances in Regional Lung Ventilation
Authors: Josué A. Victorino, João B. Borges, Valdelis N. Okamoto, Gustavo F. J. Matos, Mauro R. Tucci, Maria P. R. Caramez, Harki Tanaka, Fernando Suarez Sipmann, Durval C. B. Santos, Carmen S. V. Barbas, Carlos R. R. Carvalho, Marcelo B. P. Amato
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Imbalances in regional lung ventilation, with gravity-dependent collapse and overdistention of nondependent zones, are likely associated to ventilator-induced lung injury. Electric impedance tomography is a new imaging technique that is potentially capable of monitoring those imbalances. The aim of this study was to validate electrical impedance tomography measurements of ventilation distribution, by comparison with dynamic computerized tomography in a heterogeneous population of critically ill patients under mechanical ventilation. Multiple scans with both devices were collected during slow-inflation breaths. Six repeated breaths were monitored by impedance tomography, showing acceptable reproducibility. We observed acceptable agreement between both technologies in detecting right–left ventilation imbalances (bias = 0% and limits of agreement = −10 to +10%). Relative distribution of ventilation into regions or layers representing one-fourth of the thoracic section could also be assessed with good precision. Depending on electrode positioning, impedance tomography slightly overestimated ventilation imbalances along gravitational axis. Ventilation was gravitationally dependent in all patients, with some transient blockages in dependent regions synchronously detected by both scanning techniques. Among variables derived from computerized tomography, changes in absolute air content best explained the integral of impedance changes inside regions of interest (r2 ⩾ 0.92). Impedance tomography can reliably assess ventilation distribution during mechanical ventilation.
Aberrant composition of gut microbiota of allergic infants: a target of bifidobacterial therapy at weaning?
Authors: P V Kirjavainen, T Arvola, S J Salminen, E Isolauri
Journal: Gut (2002)

<b>Background:</b> Recent data have outlined a relationship between the composition of the intestinal microflora and allergic inflammation, and demonstrated the competence of probiotics in downregulation of such inflammation. <b>Aims:</b> Our aims were to characterise the relationship between gut microbes and the extent of allergic sensitisation and to assess whether the efficacy of bifidobacterial supplementation in the treatment of allergy could relate to modulation of the intestinal microbiota. <b>Methods:</b> This randomised study included 21 infants with early onset atopic eczema of whom eight were intolerant (highly sensitised group (HSG)) and 13 tolerant (sensitised group (SG)) to extensively hydrolysed whey formula (EHF). In the SG, six were weaned to EHF without (placebo group (PG)) and seven to EHF with <i>Bifidobacterium lactis</i> Bb-12 supplementation (bifidobacteria treated group (BbG)). The faecal microflora of infants in the HSG was analysed only before weaning whereas in the SG the faecal microflora was analysed both before and after weaning. <b>Results:</b> Infants in the HSG had greater numbers of lactobacilli/enterococci than those in the SG. Serum total IgE concentration correlated directly with <i>Escherichia coli</i> counts in all infants and with bacteroides counts in the HSG, indicating that the presence of these bacteria is associated with the extent of atopic sensitisation. The effect of supplementation was characterised as a decrease in the numbers of <i>Escherichia coli</i> and protection against an increase in bacteroides numbers during weaning. <b>Conclusions:</b> These data indicate that bifidobacterial supplementation appears to modify the gut microbiota in a manner that may alleviate allergic inflammation. Further studies are needed to confirm this conclusion.
The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials
Authors: W Zhang, J Robertson, A C Jones, P A Dieppe, M Doherty
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To examine the placebo effect and its potential determinants in the treatment of osteoarthritis (OA) via a systematic literature search of Medline, EMBASE, Scientific Citation Index, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Library. <h3>Methods:</h3> Randomised placebo controlled trials in OA were included. The placebo effect was defined as the overall change from baseline in the placebo group. It was estimated as the effect size (ES; the standard mean difference between baseline and endpoint) and this was compared with the ES obtained from untreated control. ES for pain was the primary outcome. Statistical pooling was undertaken as appropriate and 95% CIs were used for comparison. Quality of trials was assessed and potential determinants of placebo effect were examined using multiple regression analysis. The partial regression coefficient (β) was used to present the adjusted size of the association. <h3>Results:</h3> We identified 198 trials with 193 placebo groups (16 364 patients) and 14 untreated control groups (1167 patients) that met our inclusion criteria. These included a range of therapies (non-pharmacological, pharmacological and surgical treatments). Placebo was effective at relieving pain (ES 0.51, 95% CI 0.46 to 0.55 for the placebo group and 0.03, 95% CI –0.13 to 0.18 for untreated control). Placebo was also effective at improving function and stiffness. The pain-relieving effect increased when the active treatment effect (β = 0.38, p&lt;0.001), baseline pain (0.006, p = 0.014) and sample size (0.001, p = 0.004) increased, and when placebo was given through injections/needles (0.144, p = 0.020). <h3>Conclusion:</h3> Placebo is effective in the treatment of OA, especially for pain, stiffness and self-reported function. The size of this effect is influenced by the strength of the active treatment, the baseline disease severity, the route of delivery and the sample size of the study.
The Effectiveness of Right Heart Catheterization in the Initial Care of Critically III Patients
Authors: Alfred F. Connors, Theodore Speroff, Neal V. Dawson, Charles Thomas, Frank E. Harrell, Douglas Wagner, Norman Desbiens, Lee Goldman, Albert W. Wu, Robert M. Califf, William J. Fulkerson, Humberto Vidaillet, Steven Broste, Paul Bellamy, Joanne Lynn, William A. Knaus
Journal: JAMA (1996)

<h3>Objective.</h3> —To examine the association between the use of right heart catheterization (RHC) during the first 24 hours of care in the intensive care unit (ICU) and subsequent survival, length of stay, intensity of care, and cost of care. <h3>Design.</h3> —Prospective cohort study. <h3>Setting.</h3> —Five US teaching hospitals between 1989 and 1994. <h3>Subjects.</h3> —A total of 5735 critically ill adult patients receiving care in an ICU for 1 of 9 prespecified disease categories. <h3>Main Outcome Measures.</h3> —Survival time, cost of care, intensity of care, and length of stay in the ICU and hospital, determined from the clinical record and from the National Death Index. A propensity score for RHC was constructed using multivariable logistic regression. Case-matching and multivariable regression modeling techniques were used to estimate the association of RHC with specific outcomes after adjusting for treatment selection using the propensity score. Sensitivity analysis was used to estimate the potential effect of an unidentified or missing covariate on the results. <h3>Results.</h3> —By case-matching analysis, patients with RHC had an increased 30-day mortality (odds ratio, 1.24; 95% confidence interval, 1.03-1.49). The mean cost (25th, 50th, 75th percentiles) per hospital stay was $49300 ($17000, $30500, $56600) with RHC and $35700 ($11 300, $20600, $39200) without RHC. Mean length of stay in the ICU was 14.8 (5,9, 17) days with RHC and 13.0 (4,7, 14) days without RHC. These findings were all confirmed by multivariable modeling techniques. Subgroup analysis did not reveal any patient group or site for which RHC was associated with improved outcomes. Patients with higher baseline probability of surviving 2 months had the highest relative risk of death following RHC. Sensitivity analysis suggested that a missing covariate would have to increase the risk of death 6-fold and the risk of RHC 6-fold for a true beneficial effect of RHC to be misrepresented as harmful. <h3>Conclusion.</h3> —In this observational study of critically ill patients, after adjustment for treatment selection bias, RHC was associated with increased mortality and increased utilization of resources. The cause of this apparent lack of benefit is unclear. The results of this analysis should be confirmed in other observational studies. These findings justify reconsideration of a randomized controlled trial of RHC and may guide patient selection for such a study.
Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification
Authors: Gust Verbruggen, Ruth Wittoek, Bert Vander Cruyssen, Dirk Elewaut
Journal: Annals of the Rheumatic Diseases (2011)

Adalimumab blocks the action of tumor necrosis factor-α and reduces disease progression in rheumatoid arthritis and psoriatic arthritis. The effects of adalimumab in controlling progression of structural damage in erosive hand osteoarthritis (HOA) were assessed.Sixty patients with erosive HOA on radiology received 40 mg adalimumab or placebo subcutaneously every two weeks during a 12-month randomized double-blind trial. Response was defined as the reduction in progression of structural damage according to the categorical anatomic phase scoring system. Furthermore, subchondral bone, bone plate erosion, and joint-space narrowing were scored according to the continuous Ghent University Score System (GUSSTM).The disease appeared to be active since 40.0% and 26,7% of patients out of the placebo and adalimumab group, respectively, showed at least one new interphalangeal (IP) joint that became erosive during the 12 months follow-up. These differences were not significant and the overall results showed no effect of adalimumab. Risk factors for progression were then identified and the presence of palpable soft tissue swelling at baseline was recognized as the strongest predictor for erosive progression. In this subpopulation at risk, statistically significant less erosive evolution on the radiological image (3.7%) was seen in the adalimumab treated group compared to the placebo group (14.5%) (P = 0.009). GUSSTM scoring confirmed a less rapid rate of mean increase in the erosion scores during the first 6 months of treatment in patients in adalimumab-treated patients.Palpable soft tissue swelling in IP joints in patients with erosive HOA is a strong predictor for erosive progression. In these joints adalimumab significantly halted the progression of joint damage compared to placebo.
Lipids and Glucose in Type 2 Diabetes: What About the β-Cell and the Mitochondria?
Authors: Guenther Boden, Markku Laakso
Journal: Diabetes Care (2005)

Drs. Eldor and Raz (1) assert that “high levels of FFAs [free fatty acids] have a detrimental effect on β-cell survival and insulin secretion.” We agree, but only in relation to patients who have dysfunctional β-cells, i.e., patients with pre-diabetes, impaired glucose tolerance, or type 2 diabetes (2–5). On the other …
Conversion of Thyroxine (T4) to triiodothyronine (T3) in athyreotic human subjects
Authors: Lewis E. Braverman, Sidney H. Ingbar, Kenneth Sterling
Journal: Journal of Clinical Investigation (1970)

Studies of the possibility that thyroxine (T4) is converted to 3.5,3'-triiodo-L-thyronine (T3) in the extrathyroidal tissues in man have been conducted in 13 patients, all but two of whom were athyreotic or hypothyroid, and all of whom were receiving at least physiological replacement doses of synthetic sodium-L-thyroxine.T3 was found in the sera of all patients, in concentrations ranging between 243 and 680 ng/100 ml (normal range 170-270 ng/100 ml). These concentrations were far in excess of those which would have been expected on the basis of the T3 contamination of the administered T4, as measured by the same technique employed in the analysis of serum. When oral medication was enriched with (125)I-labeled T4 for 8 or more days, labeled T3 and tetraiodothyroacetic acid (Tetrac or TA(4)) were found in the serum to the extent of approximately 2-5% of total radioactivity, as assessed by unidimensional paper chromatography. The same results were obtained with a specially purified lot of radioactive T4 containing less than 0.1% T3 as a contaminant. The identities of the (125)I-labeled T3 and TA(4) were verified by two-dimensional chromatography as well as by specific patterns of binding in serum. The labeled T3 isolated was bound by albumin and by T4-binding globulin (TBG), but not by T4-binding prealbumin (TBPA): in contrast the labeled TA(4) was bound by albumin and TBPA, but not by TBG. To exclude the possibility that the conversion of T4 to T3 was a peculiarity of the oral route of administration, the sera of two additional patients were obtained 48 hr after 7-day courses of daily intravenous injections of a mixture of stable and (125)I-labeled T4. Both stable and labeled T3 were likewise found in these sera. In contrast to earlier experiments in humans in which (131)I-labeled T3 was not definitively demonstrated in serum after a single intravenous injection of (131)I-labeled T4, the present findings are taken to provide conclusive evidence of the extrathyroidal conversion of T4 to T3 in man. These results raise once again the question of the extent to which the metabolic effect of T4 is mediated through the peripheral generation of T3.
Autoantibody “Subspecificity” in Type 1 Diabetes
Authors: Jennifer M. Barker, Jeesuk Yu, Liping Yu, Jian Wang, Dongmei Miao, Fei Bao, Edward Hoffenberg, Jerald C. Nelson, Peter A. Gottlieb, Marian Rewers, George S. Eisenbarth
Journal: Diabetes Care (2005)

OBJECTIVE—Autoimmune thyroid disease (AIT), celiac disease, and Addison’s disease are characterized by the presence of autoantibodies: thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in AIT, tissue transglutaminase antibody (TTGAb) in celiac disease, and 21-hydroxylase antibody (21-OHAb) in Addison’s disease. The objective of this study was to define the prevalence of these autoantibodies and clinical disease in a population with type 1 diabetes. RESEARCH DESIGN AND METHODS—We screened 814 individuals with type 1 diabetes for TPOAb, TGAb, TTGAb, and 21-OHAb. Clinical disease was defined by chart review. Factors related to the presence of autoimmunity and clinical disease including age at onset of type 1 diabetes, duration of diabetes, age at screening, sex, and the presence of autoantibodies were reviewed. RESULTS—The most common autoantibodies expressed were TPOAb and/or TGAb (29%), followed by TTGAb (10.1%) and 21-OHAb (1.6%). Specific HLA DR/DQ genotypes were associated with the highest risk for expression of 21-OHAb (DRB1*0404-DQ8, DR3-DQ2) and TTGAb (DR3-DQ2- DR3-DQ2). The expression of thyroid autoantibodies was related to 21-OHAb but not to TTGAb. The presence of autoantibodies was associated with and predictive of disease. CONCLUSIONS—In this large cohort of individuals with type 1 diabetes, the expression of organ-specific autoantibodies was very high. The grouping of autoantibody expression suggests common factors contributing to the clustering.
Hepatic interferon-α gene transcripts and products in liver specimens from acute and chronic hepatitis B virus infection
Authors: Kayhan T. Nouri-Aria, Joachim Arnold, Fergus Davison, Bernard C. Portmann, Anthony Meager, Alan G. Morris, Graeme J. M. Alexander, Adrian L. W. F. Eddleston, Roger Williams
Journal: Hepatology (1991)

In this study we have examined the localization of interferon-alpha in liver tissue from acute and chronic hepatitis B virus carriers to establish whether the defect in interferon-alpha production reported in chronic hepatitis B virus infection is at a pretranscriptional or posttranscriptional level using in situ hybridization and immunohistochemical techniques. Interferon-alpha messenger RNA transcripts and the immunoreactive protein were abundant in liver tissue and in particular in hepatocytes from patients with acute hepatitis B virus infection who subsequently recovered. In contrast interferon-alpha polypeptide was present in a significantly lower number of sinusoidal cells, mononuclear cells and hepatocytes in chronic hepatitis B virus carriers. Although a high proportion of patients with chronic hepatitis B virus infection had cells that expressed interferon-alpha messenger RNA transcripts, the number of such cells was significantly less than in acute hepatitis B virus infection, indicating that the defect in the hepatic interferon-alpha synthesis is at the level of gene activation. Furthermore, using double immunohistochemical staining, the number of hepatocytes containing HBcAg correlated inversely with the proportion of neighboring sinusoidal cells expressing interferon-alpha. These data support previous observations that interferon-alpha production is reduced in chronic hepatitis B virus infection and are consistent with the view that this cytokine is important in the clearance of the virus.
Discriminating sputum-eosinophilic asthma: Accuracy of cutoffs in blood eosinophil measurements versus a composite index, ELEN
Authors: Deepak B Khatry, David L Gossage, Gregory P Geba, Joseph M Parker, Nizar N Jarjour, William W Busse, Nestor A Molfino
Journal: Journal of Allergy and Clinical Immunology (2015)
Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience.
Authors: W R Connell, M A Kamm, J K Ritchie, J E Lennard-Jones
Journal: Gut (1993)

Myelosuppression is an important and potentially lethal complication of azathioprine treatment. The blood count has been reviewed in all patients treated with azathioprine for inflammatory bowel disease over 27 years in one hospital. Altogether 739 patients (422 with Crohn9s disease, 284 with ulcerative colitis, and 33 with indeterminate colitis) were treated with 2 mg/kg/day azathioprine for a median of 12.5 months (range 0.5-132) between 1964 and 1991. Full blood counts were performed monthly for the duration of treatment. In 37 patients (5%) who developed bone marrow toxicity, the drug was withdrawn or the dose reduced. Thirty two of these patients were asymptomatic and five developed symptoms. Leucopenia (white blood count less than 3.0 x 10g/l) occurred in 28 (3.8%) patients, in nine of whom it was severe (white blood count &lt; 2.0 x 10(9)/l). Of these nine patients, three were pancytopenic: two died from sepsis and the other had pneumonia but recovered. A further two patients with severe leucopenia developed a mild upper respiratory infection only. Thrombocytopenia (platelet count &lt; 100,000 x 10(6)/l) in 15 patients was associated with leucopenia in six and developed in isolation in a further nine (total 2%). Isolated thrombocytopenia was never clinically severe. Myelotoxicity from azathioprine developed at any time during drug treatment (range 2 weeks-11 years after starting the drug) and occurred either suddenly or over several months. Bone marrow suppression as a result of azathioprine treatment is uncommon when a moderate dose is used, but is potentially severe. Leucopenia is the commonest and most important haematological complication. Regular monitoring of the full blood count is recommended during treatment.
<i>Clostridium difficile</i> Infection
Authors: Daniel A. Leffler, J. Thomas Lamont
Journal: New England Journal of Medicine (2015)

This article reviews the pathogenesis, epidemiology, diagnosis, and treatment of this nosocomial and potentially fatal infectious diarrhea, as well as the associated risk factors. New treatments include fecal microbiota transplantation for disease that is resistant to vancomycin.
International Union of Pharmacology. LIV. Nomenclature and Molecular Relationships of Inwardly Rectifying Potassium Channels
Authors: Yoshihiro Kubo, John P. Adelman, David E. Clapham, Lily Y. Jan, Andreas Karschin, Yoshihisa Kurachi, Michel Lazdunski, Colin G. Nichols, Susumu Seino, Carol A. Vandenberg
Journal: Pharmacological Reviews (2005)

Since the initial cDNA cloning of the first inward rectifiers Kir1.1 (ROMK1) and Kir2.1 (IRK1) in 1993, a succession of new members of this family have been identified, including the G protein-coupled Kir3 and the ATP-sensitive Kir6. These channels play an important physiological role in the