tbuckley/cabot-search huggingface dataset:
Epithelial Pten Controls Acute Lung Injury and Fibrosis by Regulating Alveolar Epithelial Cell Integrity
Authors: Kahori Miyoshi, Shigehisa Yanagi, Kohichi Kawahara, Miki Nishio, Hironobu Tsubouchi, Yoshifumi Imazu, Ryusuke Koshida, Nobuhiro Matsumoto, Akiko Taguchi, Shu-ichi Yamashita, Akira Suzuki, Masamitsu Nakazato
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Injury to alveolar epithelial cells (AECs) and to their repair process is integral to the pathogenesis of acute lung injury (ALI) and idiopathic pulmonary fibrosis (IPF). The mechanisms regulating the integrity of AECs and their intrinsic regulators remain unclear. Pten is a tumor suppressor, and its function in epithelial cells during organ fibrosis is unknown.Objectives: To determine the role of epithelial Pten in ALI and lung fibrosis.Methods: Bronchioalveolar epithelium–specific Pten-deleted SP-C-rtTA/(tetO)7-Cre/PtenΔ/Δ (SOPtenΔ/Δ) mice were studied by structural, biochemical, and physiologic analyses and compared with wild-type mice. Further mechanistic studies were performed in vivo, in vitro, and on samples from patients with IPF.Measurements and Main Results: SOPtenΔ/Δ mice demonstrated exacerbated alveolar flooding and subsequent augmented lung scarring with enhanced disassembly of tight junctions (TJs) of AECs and degradation of basement membranes. The induction of dominant negative PTEN gene in lung epithelial cells led to augmented transforming growth factor-1–induced disruptions of TJs. Epithelial-derived myofibroblasts were increased in the epithelium-specific Pten-deficient mice. The lungs of bleomycin-treated SOPtenΔ/Δ mice showed increased pAkt, pS6K, Snail, and matrix metalloproteinase expressions and decreased claudin-4, E-cadherin, and laminin-β1 expressions. Akt inactivation definitively saved SOPtenΔ/Δ mice through amelioration of ALI and retention of AEC integrity. We detected a reduction of PTEN expression and AKT hyperactivation in the AECs of human IPF lungs.Conclusions: Our results highlight epithelial Pten as a crucial gatekeeper controlling ALI and lung fibrosis by modulating AEC integrity, and the Pten/PI3K/Akt pathway as a potential therapeutic target in these intractable diseases.
Obstetricians defend safety of childbirth in Italy
Authors: M. Day
Journal: BMJ (2010)

Six of Italy’s most senior obstetricians have claimed in an open letter to a national newspaper that their profession is under attack after the press coverage of a series of high profile neonatal incidents in which mothers or babies have died or been injured.

In August it was reported that a baby died shortly after a difficult birth at Rome’s Policlinico Casilino hospital. The parents say that a row between two attending doctors allowed fatal delays in care. And in September the press reported the deaths of two mothers, in Milan and in Matera, in the southern region of Basilicata, after multiple births.

In three other incidents in the past …
Evidence that Growth factor independence 1b regulates dormancy and peripheral blood mobilization of hematopoietic stem cells
Authors: Cyrus Khandanpour, Ehssan Sharif-Askari, Lothar Vassen, Marie-Claude Gaudreau, Jinfang Zhu, William E. Paul, Taro Okayama, Christian Kosan, Tarik Möröy
Journal: Blood (2010)
Adenoviral E1A Function through Myc
Authors: Abhishek A. Chakraborty, William P. Tansey
Journal: Cancer Research (2008)

The study of DNA tumor viruses has been invaluable in uncovering the cellular nodes and pathways that contribute to oncogenesis. Perhaps one of the best-studied oncoproteins encoded by a DNA tumor virus is adenovirus E1A, which modifies the function of key regulatory proteins such as retinoblastoma (Rb) and the chromatin remodeling protein p400. Although the interaction of E1A with Rb has long been known to target regulation of the E2F transcription factors, the downstream target of the E1A-p400 interaction has remained elusive. We have recently reported that a critical downstream link of the E1A-p400 nexus is the oncoprotein transcription factor c-Myc. Through its interaction with p400, E1A stabilizes Myc and promotes formation of Myc-p400 complexes on chromatin, leading to activation of Myc target genes. These findings point to an important role for p400 in Myc function and reveal that E1A drives oncogenesis by tapping into two important transcriptional networks: those of E2F and Myc.
STUDIES CONCERNING THE SITE OF RENIN FORMATION IN THE KIDNEY
Authors: Meyer Friedman, A. Kaplan
Journal: The Journal of Experimental Medicine (1942)

1. The absence of glomeruli in the kidney of the midshipman fish (Porichthys notatus) is reported. 2. The detection of renin in the glomerular kidney of the carp, the catfish, and the hog, and the apparent absence of this substance in the aglomerular kidney of the midshipman fish suggest that the tubular portion of the mammalian kidney does not produce or store renin.
Substitution Rates in the X- and Y-Linked Genes of the Plants, Silene latifolia and S. dioica
Authors: Dmitry A. Filatov, Deborah Charlesworth
Journal: Molecular Biology and Evolution (2002)

Theory predicts that selection should be less effective in the nonrecombining genes of Y-chromosomes, relative to the situation for genes on the other chromosomes, and this should lead to the accumulation of deleterious nonsynonymous substitutions. In addition, synonymous substitution rates may differ between X- and Y-linked genes because of the male-driven evolution effect and also because of actual differences in per-replication mutation rates between the sex chromosomes. Here, we report the first study of synonymous and nonsynonymous substitution rates on plant sex chromosomes. We sequenced two pairs of sex-linked genes, SlX1-SlY1 and SlX4-SlY4, from dioecious Silene latifolia and S. dioica, and their non–sex-linked homologues from nondioecious S. vulgaris and Lychnis flos-jovis, respectively. The rate of nonsynonymous substitutions in the SlY4 gene is significantly higher than that in the SlX4 gene. Silent substitution rates are also significantly higher in both Y-linked genes, compared with their X-linked homologues. The higher nonsynonymous substitution rate in the SlY4 gene is therefore likely to be caused by a mutation rate difference between the sex chromosomes. The difference in silent substitution rates between the SlX4 and SlY4 genes is too great to be explained solely by a higher per-generation mutation rate in males than females. It is thus probably caused by a difference in per-replication mutation rates between the sex chromosomes. This suggests that the local mutation rate can change in a relatively short evolutionary time.
Idiopathic Pulmonary Fibrosis
Authors: Katerina M. Antoniou, David M. Hansell, Michael B. Rubens, Katharina Marten, Sujal R. Desai, Nikolaos M. Siafakas, Andrew G. Nicholson, Roland M. du Bois, Athol U. Wells
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

The pathogenic importance of smoking status in idiopathic pulmonary fibrosis (IPF) is uncertain. In theory, increased oxidative stress in current and former smokers might promote disease progression. However, better survival has been reported for current smokers with IPF, although this might reflect less severe disease at presentation (a "healthy smoker effect").To determine whether smoking status is associated with survival differences in IPF.A total of 249 patients with IPF were studied (current smokers, n = 20; former smokers, n = 166; never-smokers, n = 63). Survival was evaluated against smoking status, using proportional hazards analysis, adjusting for sex, age, disease severity (extent of the disease on high-resolution computed tomography, composite physiologic index [CPI], percentage predicted diffusing capacity for carbon monoxide in separate models), and the degree of honeycombing.Current smokers had milder disease than did former smokers, with lower CPI scores (P < 0.0001), less extensive disease on high-resolution computed tomography (P < 0.005), and higher unadjusted survival (hazard ratio = 0.44; 95% confidence interval = 0.24, 0.80; P = 0.007). However, survival did not differ between current and former smokers (P = 0.39) after adjustment for CPI levels. By contrast, the increase in survival seen in nonsmokers than in former smokers (hazard ratio = 0.51; 95% confidence interval = 0.41, 0.83; P = 0.008) was amplified (P < 0.0005) by adjustment for CPI levels.In IPF, survival and severity-adjusted survival are higher in nonsmokers than in former smokers or the combined group of former and current smokers. By contrast, a better outcome in current smokers, compared with former smokers, reflects less severe disease at presentation and may represent a healthy smoker effect.
Characterization of autoantibodies against the platelet glycoprotein antigens llb/llla in childhood idiopathic thrombocytopenia purpura
Authors: Jeffrey W. Taub, Indira Warrier, Christine Holtkamp, Diana S. Beardsley, Jeanne M. Lusher
Journal: American Journal of Hematology (1995)

The majority of children with idiopathic thrombocytopenia (ITP) have an acute self-limiting course and no diagnostic test has been identified which will predict the course of thrombocytopenia and detect those with the chronic autoimmune form. The detection of autoantibodies directed against the platelet glycoprotein complex IIB/IIIa, may identify patients with chronic ITP. Serum anti-GP IIb/IIIa antibodies were assessed by the indirect MAIPA assay in 54 children with immune thrompocytopenia at initial presentation along with an additional 7 children previously diagnosed with chronic ITP, to determine if there was a difference in antibody positivity between acute and chronic ITP patients, and whether the identification of antibodies could be used as a predictive test at diagnosis. There was no significant difference in the percentage of antibodies detected in children classified with acute ITP (27/40-68%) compared to children with chronic ITP (13/21-62%, P > 0.05). Patients with acute ITP had significantly lower mean platelet counts at diagnosis compared to the chronic ITP group (16,225/mm3 vs 32,250/mm3, P < 0.05), though there was no significant difference in the bleeding manifestations between the acute and chronic ITP groups. Serum anti-GP IIb/IIIa antibodies are detected in a high percentage of children with ITP and autoantibodies appear to be involved in the pathogenesis of both acute and chronic ITP. The detection of anti-GP IIb/IIIa antibodies at diagnosis, however, does not appear to be a useful prognostic test in childhood ITP.
Dual Cutaneous Reactions to Anti‐Human IgE; No Change in Plasma Level of the Split Product Complement C3d or Effect of Heparin
Authors: Grönneberg R
Journal: Allergy (1985)

The possible dependence of the dual cutaneous reaction (DCR) on activation of the complement and coagulation systems was further elucidated. Heterologous whole anti‐human IgE was injected intradermally (i.d.) on the volar aspect of the forearms of 17 drug‐free healthy volunteers and venous samples for the selected laboratory test collected from the adjacent cubital vein. Plasma level of C3 split products (C3d) did not change significantly 6 h and 96 h after the injection of anti‐IgE inducing immediate cutaneous reactions (ICRs) or DCRs as compared with prechallenge values. Conventional heparin, a compound with anti‐coagulant and anti‐complementary effects, injected i.d. (200 IE) concomitantly with and by s.c. (1000 IE) infiltration of the whealing 15 and 90 min subsequently to anti‐IgE challenge produced no significant inhibition of the resulting ICRs or DCRs. The results suggest that the previously reported involvement of the coagulation process is a secondary phenomenon and do not support the concept that activation of the complement system is necessary for the evolution of DCRs.
Attenuation Correction of Somatostatin Receptor SPECT by Integrated Low-Dose CT
Authors: Ingo G. Steffen, Sebastian Mehl, Friederike Heuck, Florian Elgeti, Christian Furth, Holger Amthauer, Juri Ruf
Journal: Clinical Nuclear Medicine (2009)

Aim: Somatostatin receptor scintigraphy (SRS) is an established imaging modality for neuroendocrine tumors (NET). Additional single photon emission computed tomography (SPECT-CT) not only permits image fusion but also attenuation correction (AC) of SPECT data. This study evaluated whether attenuation corrected SPECT-images (SPECT[AC]) are more sensitive than nonattenuation corrected SPECT-reconstructions (SPECT[NAC]) for the detection of NET lesions. Methods: The imaging data (planar In-111-octreotide scintigraphy and SPECT-CT) of 50 consecutive patients (28 male; 22 female; age, 34–80; mean, 65 years) with NET were included in this retrospective analysis. SPECT data were reconstructed with and without integrated CT-based AC and then analyzed by 2 experienced readers for the presence of pathologic uptake in a blinded consensus reading. Fused SPECT-CT, contemporary CT/MRI, and clinical as well as imaging follow-up served as a reference standard. All foci were rated in both the SPECT(NAC)- and SPECT(AC)-reconstructions for intensity and contrast using a 6-point-score (“0 = no uptake/no delineation from surrounding tissue” to “5 = very high uptake/very strong delineation from surrounding tissue”). The scores were analyzed in a 6 × 6 contingency table using the McNemar Bowker test. Results: A total of 222 pathologic foci were detected by SPECT(NAC) and 227 foci by SPECT(AC), respectively. In 67 of 227 foci (29.5%), focus intensity/contrast increased after AC, whereas only 5 foci showed a decrease (P < 0.001). Sensitivity increased by 2.2% (P = 0.025; 95% CI: 0.02%–4.1%) as 5 foci were detected only by SPECT(AC). However, as these 3 patients were already diagnosed with systemic disease, there was no influence on the therapeutic strategy chosen. Conclusion: Attenuation correction of somatostatin receptor scintigraphy-SPECT significantly improves focus visualization and, albeit slightly, also significantly increases sensitivity.
The Familial Occurrence of the Mid-Late Systolic Click—Late Systolic Murmur Syndrome.
Authors: William Shell
Journal: Annals of Internal Medicine (1968)

s1 May 1968The Familial Occurrence of the Mid-Late Systolic Click—Late Systolic Murmur Syndrome.William Shell, M.D., Park W. Willis III, M.D., F.A.C.P., Mary E. Clifford, M.D., F.A.C.P., Joseph A. Walton Jr., M.D.William Shell, M.D.Search for more papers by this author, Park W. Willis III, M.D., F.A.C.P.Search for more papers by this author, Mary E. Clifford, M.D., F.A.C.P.Search for more papers by this author, Joseph A. Walton Jr., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1161_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe pedigrees of 4 families are reported in which mid or late systolic extra sounds, late systolic murmurs, pansystolic murmurs, and abnormal electrocardiograms showed a familial pattern. Each propositus came to attention because of a systolic extra sound and a late systolic murmur. In 31 members of the four families studied, 11 mid or late systolic extra sounds, 7 late systolic murmurs, 8 pansystolic murmurs, and 8 "abnormal" electrocardiograms were found. The prevalence of these abnormalities ranged from 50 to 100% in the 4 families. In 3 of the families there were instances of unexplained sudden death before age 30.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Ann Arbor, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1161-1161KeywordsElectrocardiographySystolic ejection murmur Issue Published: 1 May 1968 PDF downloadLoading ...
Osteogenesis on nanoparticulate mineralized collagen scaffolds via autogenous activation of the canonical BMP receptor signaling pathway
Authors: Xiaoyan Ren, David Bischoff, Daniel W. Weisgerber, Michael S. Lewis, Victor Tu, Dean T. Yamaguchi, Timothy A. Miller, Brendan A.C. Harley, Justine C. Lee
Journal: Biomaterials (2015)
Anti-infective research and development—problems, challenges, and solutions
Authors: John S Bradley, Robert Guidos, Steve Baragona, John G Bartlett, Ethan Rubinstein, George G Zhanel, Michael D Tino, David L Pompliano, Frank Tally, Praveen Tipirneni, Glenn S Tillotson, John H Powers, Glenn S Tillotson
Journal: The Lancet Infectious Diseases (2006)
Lymphoma After Solid Organ Transplantation: Risk, Response to Therapy, and Survival at a Transplantation Center
Authors: Jason S. Knight, Alexander Tsodikov, Diane M. Cibrik, Charles W. Ross, Mark S. Kaminski, Douglas W. Blayney
Journal: Journal of Clinical Oncology (2009)

We studied the incidence, risk factors, treatment, and outcomes of post-transplantation lymphoproliferative disorder (PTLD) that occurred at the University of Michigan since 1964.We identified 7,040 patients who received solid organ transplantation (SOT) and post-transplantation immunosuppressive therapy. Seventy-eight patients developed PTLD.Diffuse large B-cell lymphoma (n = 43), polymorphic PTLD (n = 10), Hodgkin's lymphoma (n = 7), Burkitts lymphoma (n = 6), plasmacytoma (n = 5), and mucosa-associated lymphoid tissue lymphoma (n = 3) were all over-represented in the SOT population compared with a population sample from the Surveillance, Epidemiology, and End Results (SEER) database; follicular lymphoma (n = 0) was underrepresented. Negative pretransplantation Epstein-Barr virus (EBV) serology was a risk factor for PTLD. Available histologic analysis of tumor tissue showed that 75% were CD20 positive and that 62% were EBV positive; EBV-positive tumors occurred sooner after SOT than EBV-negative tumors (mean, 29 v 66 months). Extralymphatic disease (79%), poor performance status (68%), elevated lactate dehydrogenase (LDH; 71%), and advanced stage (68%) disease were all common at the time of lymphoma diagnosis. Two thirds of patients had a complete response when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone-like chemotherapy (either with or without rituximab). Median overall survival in all patients with PTLD was 8.23 years (95% CI, 2.28 to 30.0 years).EBV-naïve patients who receive a donor organ from an EBV-infected donor are in the highest-risk situation for PTLD development. Most of these lymphomas are CD20 positive. Follicular lymphoma is unusual. With treatment, survival of patients with PTLD was indistinguishable from that of the SEER population sample.
Tricuspid Leaflet Aortic Valve Prosthesis
Authors: BENSON B. ROE, PAUL B. KELLY, JOHN L. MYERS, DAVID W. MOORE
Journal: Circulation (1966)

The theoretical and practical advantages of the flexible-leaflet prosthetic aortic valve make it worthy of continued development. Laboratory and clinical experience with a precision-molded, single-unit, tricuspid silicone rubber prosthesis suggest that the problems of materials, construction, and performance have been overcome. The use of a suitable elastomer in a precision casting with an anticlotting surface coating has resulted in a leaflet prosthesis the long-term functional performance of which should compare favorably with any device currently in use.
ACUTE VASCULAR LESIONS IN MICE FOLLOWING INJECTIONS OF PNEUMOCOCCI
Authors: T. P. Sprunt, J. A. Luetscher
Journal: The Journal of Experimental Medicine (1912)

Mice dying several days after injections of pneumococci, both living and dead, frequently show at autopsy large intrathoracic hemorrhages. The histological study of the thoracic organs indicates that there occurs in each case a sharply circumscribed, acute degeneration of the wall of some large vessel, usually the ascending aorta or one of the pulmonary arteries. This degenerated portion is torn out by the pressure of the blood with almost complete disappearance of the vessel wall, leading to a gross hemorrhage. A similar change is occasionally found in the walls of the veins which contain cardiac instead of smooth muscle. We have found this lesion only in mice which had been recently inoculated with pneumococci. Negative cultures at autopsy, the lack of inflammatory reaction, and the occurrence of the conditions after injection of dead pneumococci suggest the cause to be a toxic degeneration of the vessel wall brought about by the poisons of the injected organisms.
Antibiotic-induced dysbiosis alters host-bacterial interactions and leads to colonic sensory and motor changes in mice
Authors: M Aguilera, M Cerdà-Cuéllar, V Martínez
Journal: Gut Microbes (2014)

Alterations in the composition of the commensal microbiota (dysbiosis) seem to be a pathogenic component of functional gastrointestinal disorders, mainly irritable bowel syndrome (IBS), and might participate in the secretomotor and sensory alterations observed in these patients.We determined if a state antibiotics-induced intestinal dysbiosis is able to modify colonic pain-related and motor responses and characterized the neuro-immune mechanisms implicated in mice. A 2-week antibiotics treatment induced a colonic dysbiosis (increments in Bacteroides spp, Clostridium coccoides and Lactobacillus spp and reduction in Bifidobacterium spp). Bacterial adherence was not affected. Dysbiosis was associated with increased levels of secretory-IgA, up-regulation of the antimicrobial lectin RegIIIγ, and toll-like receptors (TLR) 4 and 7 and down-regulation of the antimicrobial-peptide Resistin-Like Molecule-β and TLR5. Dysbiotic mice showed less goblet cells, without changes in the thickness of the mucus layer. Neither macroscopical nor microscopical signs of inflammation were observed. In dysbiotic mice, expression of the cannabinoid receptor 2 was up-regulated, while the cannabinoid 1 and the mu-opioid receptors were down-regulated. In antibiotic-treated mice, visceral pain-related responses elicited by intraperitoneal acetic acid or intracolonic capsaicin were significantly attenuated. Colonic contractility was enhanced during dysbiosis. Intestinal dysbiosis induce changes in the innate intestinal immune system and modulate the expression of pain-related sensory systems, an effect associated with a reduction in visceral pain-related responses. Commensal microbiota modulates gut neuro-immune sensory systems, leading to functional changes, at least as it relates to viscerosensitivity. Similar mechanisms might explain the beneficial effects of antibiotics or certain probiotics in the treatment of IBS.
Removal of extruded I.U.D.
Authors: U E Mountrose, W L Whitehouse
Journal: BMJ (1972)

2 case histories of extrusion of an IUD through the uterine muscle into the pouch of Douglas are described.  Colpotomy was performed to remove the IUDs.  Both patients had a painfree uncomplicated postoperative recovery and were released from the hospital within 48 hours.  Colpotomy is recommended for cases of extrusion into the pouch of Douglas instead of the more complicated procedures of laparotomy or laparoscopy.