tbuckley/cabot-search huggingface dataset:
Malignant mesothelioma vs metastatic carcinoma of pleura: Do pathology and radiology agree?
Authors: Mehrdad Bakhshayesh, Leila Mosadegh, Shirin Karimi
Journal: European Respiratory Journal (2013)

Introduction: MPM is a rare malignant neoplasm of pleura that represents with several CT features seen in other common pleural malignancies.The aim of this study is to evaluate the agreement of radiology and pathology in differentiation between MPM and metastatic pleural malignancy and to demonstrate most characteristic CT finding of them.Material and Methods:55 patients,29males and 26females,diagnosed with MPMand metastatic pleural malignancies were enrolled in the retrospective studyThe diagnoses were made by pathology based on immuno histo chemistry study.All CT scans were observed to evaluate several parameters and the most probable diagnosis.Results:17 MPM and 38 metastatic pleural malignancies based on pathology and22MPM and 33metastatic pleural malignancies based on radiology were reported.The most common findings suggestive of malignant pleural mesothelioma were pleural thickening(88.2%), locculated effusion(58.8%)and thickening of interlobar fissure(47.1%)whereas free pleural effusion(71.7%), parenchymal infiltration(65.8%)mostly massive and pleural thickening(63.2%)were most prevalent parameter of metastatic cases. Regarding differentiating between MPMand metastatic pleural malignancy by pathology and radiology,kappa coefficient was 0.56 in our study which indicates moderate agreement.Conclusion: considering P-value
Is fibrillation chaos?
Authors: D T Kaplan, R J Cohen
Journal: Circulation Research (1990)

Ventricular fibrillation is examined to determine whether it is an instance of deterministic chaos. Surface ECGs from dogs in fibrillation were used to generate a state space representation of fibrillation. Our analysis failed to identify a low-dimensional attractor that could be associated with fibrillation. The results suggest that fibrillation is similar to a nonchaotic random signal. We note, however, that such random-looking but nonchaotic behavior can also be generated by a nonlinear deterministic system.
Connexin 30, a new marker of hyperproliferative epidermis
Authors: G. Lemaître, V. Sivan, J. Lamartine, J.-M. Cosset, B. Cavelier-Balloy, D. Salomon, G. Waksman, M.T. Martin
Journal: British Journal of Dermatology (2006)

Conflicts of interest: none declared. Sir, Gap junctions are intercellular channels that allow the passage of low molecular weight substances such as ions and second messengers between cells. These channels are formed by membrane proteins called connexins (Cx).1 In human epidermis, the gap junctions comprise mostly Cx43 and Cx26.2 The importance of gap junctions in the regulation of keratinocyte growth and differentiation has been demonstrated in wound healing3 and through the discovery of Cx mutations underlying skin disorders.4 Besides mutations, alterations in Cx expression have also been associated with hyperproliferative skin diseases such as psoriasis, where upregulation of Cx26 has been described in lesional skin.5 Cx30, although identified in human normal epidermis,2 has been poorly studied in skin. The present study addresses the question of the regulation of Cx30 expression in epidermis from patients presenting with three different types of hyperplasia: radiation‐induced hyperplasia, psoriasis and porokeratosis of Mibelli. In normal skin (breast, abdomen, foreskin; Table 1), we failed to detect any expression of the Cx30 protein in the interfollicular epidermis, whatever the anatomical skin localization (Fig. 1B). A negative Cx30 expression was also found at the margin of the lesion of one irradiated patient (inguinal region) and in the control skin of another irradiated patient (abdomen). For the latter irradiated patient, a similar result was also obtained by Western blotting and at the RNA level, as no transcript was detected in the normal abdomen skin. For the patient with porokeratosis of Mibelli, a faint expression of Cx30 was observed in the normal heel skin (Fig. 2C), as we previously described in normal palm epidermis.6 We also found faint labelling in some epidermal appendages. The expression of Cx30 was detected in sweat glands, ducts and outer root sheath of the hair follicle, with a decreased intensity from the internal to the external cell layers.7
Functional analyses of thymic CD5+ B cells. Responsiveness to major histocompatibility complex class II-restricted T blasts but not to lipopolysaccharide or anti-IgM plus interleukin 4.
Authors: M Inaba, K Inaba, Y Adachi, K Nango, H Ogata, S Muramatsu, S Ikehara
Journal: The Journal of Experimental Medicine (1990)

The function of thymic B cells in several standard in vitro assays was investigated. Thymic B cells, 75% of which were CD5+, showed a poor responsiveness to the mitogens LPS or anti-mu plus IL-4. Both proliferation and antibody formation were much lower in thymic than splenic B cell cultures. However, CD5- B cells purified using a cell sorter responded well to B cell stimulants, whereas purified CD5+ thymic B cells did not, indicating that CD5+ thymic B cells were unresponsive to B cell growth factor or LPS. Thymic B cells could be activated polyclonally by direct interaction with alloreactive T blasts, as manifested by DNA synthesis and antibody formation. These findings indicate that CD5+ thymic B cells may not be stimulated via sIg and IL-4, but require instead direct interaction with T blasts.
Viktor Hamburger and Rita Levi-Montalcini: The Path to the Discovery of Nerve Growth Factor
Authors: W. Maxwell Cowan
Journal: Annual Review of Neuroscience (2001)

▪ Abstract The announcement in October 1986 that the Nobel Prize for physiology or medicine was to be awarded to Rita Levi-Montalcini and Stanley Cohen for the discoveries of NGF and EGF, respectively, caused many to wonder why Viktor Hamburger (in whose laboratory the initial work was done) had not been included in the award. Now that the dust has settled, the time seems opportune to reconsider the antecedent studies on the relation of the developing nervous system to the peripheral structures it innervates. The studies undertaken primarily to investigate this issue culminated in the late 1950s in the discovery that certain tissues produce a nerve growth–promoting factor that is essential for the survival and maintenance of spinal (sensory) ganglion cells and sympathetic neurons. In this review, the many contributions that Viktor and Rita made to this problem, both independently and jointly, are reexamined by considering chronologically each of the relevant research publications together with some of the retrospective memoirs they have published in the years since the discovery of NGF was first reported. This review is dedicated to Viktor Hamburger on the occasion of his 100th birthday on July 9, 2000, and to Rita Levi-Montalcini to mark her 91st birthday on April 22, 2000, with admiration and affection.
Ancestors of Trans-Splicing Mitochondrial Introns Support Serial Sister Group Relationships of Hornworts and Mosses with Vascular Plants
Authors: M. Groth-Malonek
Journal: Molecular Biology and Evolution (2004)

Some group II introns in the organelle genomes of plants and algae are disrupted and require trans-splicing of the affected exons from independent transcripts. A peculiar mitochondrial nad5 gene structure is universally conserved in flowering plants where two trans-splicing introns frame a tiny exon of only 22 nucleotides, and two additional conventional group II introns interrupt the nad5 reading frame at other sites. These four introns are absent in the liverwort Marchantia polymorpha, which carries a group I intron at an unrelated site in nad5. To determine how intron gains and losses have sculptured mitochondrial gene structures in early land-plant evolution, we have investigated the full nad5 gene structures in the three bryophyte classes and the fern Asplenium nidus. We find the single Marchantia group I intron nad5i753 present as the only intervening sequence in both closely (Corsinia and Monoclea) and distantly related (Noteroclada, Bazzania, and Haplomitrium) liverwort genera. In a taxonomically wide spectrum of mosses (Sphagnum, Encalypta, Timmia, Ulota, and Rhacocarpus); however, we additionally identify the angiosperm-type group II introns nad5i230 and nad5i1455. The latter is a cis-arranged homolog to one of the two angiosperm trans-splicing introns, notably the first of its kind in mosses. In the hornwort Anthoceros, the “moss and liverwort–type” group I intron nad5i753 is absent, and, besides nad5i230 and nad5i1455, intron nad5i1477 is present as the second ancestral group II intron which has evolved into a trans-splicing arrangement in angiosperms. The influence of highly frequent RNA editing, most notably in the genera Haplomitrium, Anthoceros, and Asplenium, on phylogenetic tree construction is investigated and discussed. Taken together, the data (1) support a sister group relationship of liverworts as a whole to all other embryophytes, (2) indicate loss of a group I and serial entries of group II introns in the nad5 gene during early evolution of the nonliverwort lineage, and (3) propose a placement of hornworts as sister group to tracheophytes.
Neutral endopeptidase activity in newborn and adult rabbit tracheas
Authors: K Haver, C Gerard, L Kobzik, SA Shore
Journal: European Respiratory Journal (1997)

Neutral endopeptidase (NEP, E.C. 3.4.24.11), a widely distributed ectoenzyme, cleaves and inactivates a variety of biologically active peptides, including the tachykinin, substance P (SP). This study was undertaken to determine whether the modulation of SP airway smooth muscle contraction by NEP is age-dependent. We studied the contractile response of isolated tracheal rings from newborn and 120 day old New Zealand white rabbits. We measured NEP activity and determined immunoreactive NEP content in tracheal membrane preparations. NEP activity was then localized histochemically in sections of rabbit tracheas. In the presence of the NEP inhibitor, SCH 32615, the contractile response of isolated tracheal rings to SP was increased both in the newborn and 120 day old rabbits. However, the increase was greatest in the newborn animals. NEP activity in tracheal membrane preparations increased fivefold between the newborn and 120 day old rabbits. Western blot analysis also revealed a significant increase in the immunoreactive NEP content of these tracheal membrane preparations between the newborn and 120 day old rabbits. NEP activity, localized histochemically, was most intense in the epithelial region of the newborn animals, with a shift of activity to the subepithelial region with age. The prominent epithelial localization of neutral endopeptidase in the tracheas of these 1 day old rabbits, which we have shown to have relatively low neutral endopeptidase activity, suggests that the location of neutral endopeptidase in the airway, including proximity to relevant substance P receptors, may be critical to its function.
Expression of latent TGF-beta binding proteins and association with TGF-beta1 and fibrillin-1 following arterial injury
Authors: S Sinha
Journal: Cardiovascular Research (2002)

Objectives: Transforming growth factor-β (TGF-β), a potent regulator of wound healing and scar formation, is thought to have a key role in the response to arterial injury. Latent TGF-β binding proteins (LTBPs), members of the fibrillin superfamily, govern TGF-β1 release, targeting and activation in vitro and also play a role as structural components of fibrillin-rich microfibrils. Despite the potential of LTBPs to modulate the response to arterial injury through either or both of these mechanisms, as yet their expression and function in the injured vasculature remain poorly defined. Methods: In this study, a porcine model of coronary angioplasty was used to investigate LTBP-1 and LTBP-2 synthesis and their association with TGF-β1 and fibrillin-1. Results: After angioplasty, increased LTBP-1 and LTBP-2 immunostaining was detected in a similar distribution to increased TGF-β1 expression in the neointima and in the neoadventitia. Overnight organ cultures revealed the formation of large latent TGF-β1 complexes containing LTBP-1. Increased LTBP-1 proteolysis after arterial injury correlated with increased active and latent TGF-β levels. LTBP-2 synthesis increased in response to arterial injury but was neither present in large latent complexes nor proteolytically processed. LTBP-1 and LTBP-2 both co-localised to fibrillin-rich fibrillar structures in the neointima and adventitia. Conclusions: These data suggest that LTBP-1 may have a TGF-β1 binding role in the arterial response to injury, and that LTBP-1 and LTBP-2 may have a structural role in association with microfibrils within the developing neointimal lesion. LTBP-1 proteolysis is potentially an important regulatory step for TGF-β activation in the vasculature and inhibition of proteolysis could represent a novel therapeutic modality for controlling the arterial injury response.
Normal T lymphocytes can express two different T cell receptor beta chains: implications for the mechanism of allelic exclusion.
Authors: E Padovan, C Giachino, M Cella, S Valitutti, O Acuto, A Lanzavecchia
Journal: The Journal of Experimental Medicine (1995)

We have examined the extent of allelic exclusion at the T cell receptor (TCR) beta locus using monoclonal antibodies specific for V beta products. A small proportion (approximately 1%) of human peripheral blood T cells express two V beta as determined by flow cytometric analysis, isolation of representative clones, and sequencing of the corresponding V beta chains. Dual beta T cells are present in both the CD45R0+ and CD45R0- subset. These results indicate that dual beta expression is compatible with both central and peripheral selection. They also suggest that the substantial degree of TCR beta allelic exclusion is dependent only on asynchronous rearrangements at the beta locus, whereas the role of the pre-TCR is limited to signaling the presence of at least one functional beta protein.
Agreement between patient-reported and chart documented outcomes: Case study in COPD
Authors: Caitlyn Solem, Lavanya Sudharshan, Shawn Sun, Cynthia Macahilig, Monica Katyal, Xin Gao, Andrew Shorr
Journal: European Respiratory Journal (2013)

Objective

To describe agreement between patient (PT) report and medical chart (CH) documentation of smoking status and exacerbation frequency/severity in severe (SEV) and very SEV COPD.

Methods

Within this 2011-12 CH review/PT survey, 99 US-based pulmonologists and primary care physicians recruited physician-reported SEV or very SEV COPD PTs who had experienced a moderate (MOD) or SEV exacerbation in the last 3 months. Smoking status, 12-month exacerbation frequency, and exacerbation severity were compared between CH vs PT self-report using concordance, weighted kappa (κ) statistics, and intraclass correlation coefficients (ICC).

Results

Of 314 PTs, 25.5%/68.8% reported current/former smoking, with high PT vs CH agreement (κ=0.878). Severities of most recent PT- and CH-reported exacerbations were concordant in 79.2% (54.4% agree MOD; 24.8% agree SEV; 20.7% not concordant; κ=0.540). PTs reported a mean±SD of 2.5±2.7/1.0±1.3 MOD/SEV exacerbations vs CH-reported, 1.8±1.3/0.9±1.0, with poor to MOD agreement (MOD 41.7% concordant, ICC=0.17 [CI: 0.06-0.27]; SEV 69.7% concordant, ICC=0.54 [0.45-0.61]; total MOD/SEV 42.9% concordant; ICC=0.23 [0.12-0.33]). When not concordant, PTs tended to report more exacerbations than CH.

Conclusions

As there is a movement towards greater use of PT-reported outcomes, it is important to consider that PT experiences provide complimentary, but not identical, information vs CH. The greater number of PT vs CH-documented exacerbations may indicate underestimated exacerbation incidence and burden, but this may be attributed in part to recall bias. Low concordance between PT vs CH highlights the necessity of using multiple sources to fully understand COPD burden and outcomes.
Angiotensin II Stimulates Intercellular Adhesion Molecule-1 (ICAM-1) Expression by Human Vascular Endothelial Cells and Increases Soluble ICAM-1 Release In Vivo
Authors: L. Pastore, A. Tessitore, S. Martinotti, E. Toniato, E. Alesse, M. C. Bravi, C. Ferri, G. Desideri, A. Gulino, A. Santucci
Journal: Circulation (1999)

We evaluated whether angiotensin II (Ang II) influenced intercellular adhesion molecule (ICAM)-1 expression by human vascular endothelial cells derived from umbilical cord veins (HUVECs) and plasma soluble ICAM-1 levels in vivo.Cultured HUVECs were incubated with Ang II (from 10(-9) to 10(-6) mol/L) with or without candesartan and PD12319 (inhibitors of Ang II AT(1) and AT(2) receptors, respectively) for various times up to 4 hours. Total RNA was then extracted from HUVECs, and Northern blots were probed with a 1.9-kb ICAM-1 cDNA fragment. HUVEC supernatants were used to assess soluble ICAM-1 release by ELISA. Northern blot analysis detected a strong increase of ICAM-1 mRNA after 2-hour incubation with Ang II. The response was inhibited by candesartan. Soluble ICAM-1 release by HUVECs also increased (P<0. 002) after 2-hour Ang II stimulation. In vivo, Ang II (at an initial rate of 1.0 ng. kg(-1). min(-1), to be increased each 30 minutes by 2.0 ng. kg(-1). min(-1) to the final rate of 7.0 ng. kg(-1). min(-1)) was infused in 8 normotensive and 12 essential hypertensive individuals. In the latter, Ang II was reinfused after 4 weeks on either placebo (n=3), losartan (50 mg UID, n=5), or atenolol (50 mg UID, n=4) treatment. Plasma soluble ICAM-1 levels increased after Ang II infusion in hypertensives and normotensives (P<0.0001 after 90 minutes). Losartan reduced baseline soluble ICAM-1 levels (P<0.05) and Ang II-related ICAM-1 increments.Ang II upregulates ICAM-1 expression by HUVECs and stimulates in vitro and in vivo soluble ICAM-1 release. AT(1) receptor blockade inhibits such endothelial effects of Ang II.
Failure to Detect<i>connexin43</i>Mutations in 38 Cases of Sporadic and Familial Heterotaxy
Authors: Marinella Gebbia, Jeffrey A. Towbin, Brett Casey
Journal: Circulation (1996)

Heterotaxy results from failure to establish normal left/right asymmetry during embryonic development. Typical manifestations include complex heart defects and malpositioning of abdominal organs. Missense base substitutions clustered in a 150-base pair region of the gap-junction gene connexin43 (cx43) have been implicated in the pathogenesis of heterotaxy.cx43 was studied in 38 cases of sporadic and familial heterotaxy. A 400-base pair region containing the previously reported mutation sites was amplified and directly sequenced in 19 patients. Nineteen additional patients were tested for restriction fragments predicted by two of the previously reported missense substitutions. No difference from normal control subjects was detected in any of the patients.Randomly selected cases of heterotaxy are unlikely to be the result of mutations in cx43.
Cardiovascular Status in Long-Term Survivors of Hodgkin's Disease Treated With Chest Radiotherapy
Authors: M. Jacob Adams, Stuart R. Lipsitz, Steven D. Colan, Nancy J. Tarbell, S. Ted Treves, Lisa Diller, Nina Greenbaum, Peter Mauch, Steven E. Lipshultz
Journal: Journal of Clinical Oncology (2004)

Cardiovascular status was assessed in 48 Hodgkin's disease (HD) survivors at a median of 14.3 years (range, 5.9 to 27.5 years) after diagnosis because they may be at increased risk for cardiovascular abnormalities.Patients completed the Short-Form 36 quality-of-life instrument and were screened by echocardiography, exercise stress testing, and resting and 24-hour ECG.All patients received mediastinal irradiation (median, 40.0 Gy; range, 27.0 to 51.7 Gy) at a median age of 16.5 years (range, 6.4 to 25.0 years). Four patients received an anthracycline. Although every patient described their health as good or better, and none had symptomatic heart disease at screening, all but one had cardiac abnormalities on screening. Restrictive cardiomyopathy was suggested by reduced average left ventricular (LV) dimension (P < .001) and mass (P < .001), without increased LV wall thickness. Significant valvular defects were present in 42%; 75% had conduction defects. One survivor developed complete heart block shortly after the study visit. Autonomic dysfunction was suggested by a monotonous heart rate in 57%, persistent tachycardia in 31%, and blunted hemodynamic responses to exercise in 27%. Peak oxygen uptake (VO2max) during exercise, a predictor of mortality in heart failure, was significantly reduced (< 20 mL/kg/m2) in 30% of survivors. VO2max was correlated with increasing fatigue, increasing shortness of breath (both, r = -0.35; P =. 02), and decreasing physical component score on the SF-36 (r = 0.554; P = .00017).A variety of unsuspected, clinically significant cardiovascular abnormalities are common in long-term survivors of HD who are treated at a young age with mediastinal irradiation. We recommend serial, comprehensive cardiac screening of HD survivors who fit this profile.
A homoharringtonine-based induction regimen for the treatment of elderly patients with acute myeloid leukemia: a single center experience from China
Authors: Jianmin Wang, Shuqing Lü, Jianmin Yang, Xianmin Song, Li Chen, Chongmei Huang, Jun Hou, Weiping Zhang
Journal: Journal of Hematology & Oncology (2009)

The response to remission induction in elderly patients with acute myeloid leukemia (AML) remains poor. The purpose of this paper is to evaluate the efficacy and toxicity of a plant alkaloid, homoharringtonine, in combination with cytarabine as an induction therapy for AML in elderly patients (> or =60 years).Twenty-three patients were treated with the HA regimen consisting of homoharringtonine (2 mg/m2/day for 7 days) and cytarabine (Ara-C, 100 mg/m2/day for 7 days). The overall response rate was 56.5% with complete remission (CR) rate of 39.1% and partial remission of 17.4%. There was no early death in this cohort of patients. The estimated median overall survival (OS) time of all patients was (12.0 +/- 3.0) months. The estimated OS time of the CR patients was 15 months. The estimated one-year OS rate of all patients treated with HA protocol was (49.3 +/- 13.5) %. The estimated one-year OS rate of the CR patients was (62.5 +/- 17.1) %.HA is a suitable induction regimen for elderly patients with AML, with relatively low toxicity and reasonable response rate.
Restimulation-induced apoptosis of T cells is impaired in patients with X-linked lymphoproliferative disease caused by SAP deficiency
Authors: Andrew L. Snow, Rebecca A. Marsh, Scott M. Krummey, Philip Roehrs, Lisa R. Young, Kejian Zhang, Jack van Hoff, Deepali Dhar, Kim E. Nichols, Alexandra H. Filipovich, Helen C. Su, Jack J. Bleesing, Michael J. Lenardo
Journal: Journal of Clinical Investigation (2009)

X-linked lymphoproliferative disease (XLP) is a rare congenital immunodeficiency that leads to an extreme, usually fatal increase in the number of lymphocytes upon infection with EBV. It is most commonly defined molecularly by loss of expression of SLAM-associated protein (SAP). Despite this, there is little understanding of how SAP deficiency causes lymphocytosis following EBV infection. Here we show that T cells from individuals with XLP are specifically resistant to apoptosis mediated by TCR restimulation, a process that normally constrains T cell expansion during immune responses. Expression of SAP and the SLAM family receptor NK, T, and B cell antigen (NTB-A) were required for TCR-induced upregulation of key pro-apoptotic molecules and subsequent apoptosis. Further, SAP/NTB-A signaling augmented the strength of the proximal TCR signal to achieve the threshold required for restimulation-induced cell death (RICD). Strikingly, TCR ligation in activated T cells triggered increased recruitment of SAP to NTB-A, dissociation of the phosphatase SHP-1, and colocalization of NTB-A with CD3 aggregates. In contrast, NTB-A and SHP-1 contributed to RICD resistance in XLP T cells. Our results reveal what we believe to be novel roles for NTB-A and SAP in regulating T cell homeostasis through apoptosis and provide mechanistic insight into the pathogenesis of lymphoproliferative disease in XLP.