tbuckley/cabot-search huggingface dataset:
Evolution of Soldier-Specific Venomous Protease in Social Aphids
Authors: M. Kutsukake, N. Nikoh, H. Shibao, C. Rispe, J.-C. Simon, T. Fukatsu
Journal: Molecular Biology and Evolution (2008)

In social aphids of the genus Tuberaphis a cysteine protease gene of the family cathepsin B exhibits soldier-specific expression and intestinal protease production. The product is orally excreted and injected by soldier nymphs into natural enemies, thereby exerting an insecticidal activity. In an attempt to gain insights into when and how the novel venomous protease for the altruistic caste has evolved, we investigated the soldier-specific type (S-type) and nonspecific type (N-type) cathepsin B genes from social and nonsocial aphids. All the social aphids examined, representing the genera Tuberaphis, Astegopteryx, and Cerataphis, possessed both the S-type and N-type genes. Phylogenetically distant nonsocial aphids also possessed cathepsin B genes allied to the S-type and the N-type, indicating the evolutionary origin of these genes in the common ancestor of extant aphids. In Tuberaphis species the S-type genes exhibited significant soldier-specific expression and accelerated molecular evolution whereas the N-type genes did not. In Astegopteryx and Cerataphis species, meanwhile, both the S-type and N-type genes exhibited neither remarkable soldier-specific expression nor accelerated molecular evolution. These results suggest that the S-type gene acquired the soldier-specific expression and the venom function after divergence of the genus Tuberaphis. On the structural model of the S-type protease of Tuberaphis styraci the accelerated molecular evolution was associated with the molecular surface rather than the catalytic cleft, suggesting that the venom activity was probably acquired by relatively minor modifications on the molecular surface rather than by generation of a novel active site. In Cerataphis jamuritsu the S-type gene was, although containing a stop codon, structurally almost intact and still transcribed, suggesting recent pseudogenization of the gene copy and possible relevance to relaxed functional constraint in the highly multiplied protease gene family. On the basis of these results we suggest that the massive amplification in aphid cathepsin B genes might have predisposed the evolution of venomous protease in the social aphid lineage and argue that gene duplication, accelerated molecular evolution, and acquisition of novel gene function must have played considerable roles in the evolution of complex biological systems including insect sociality.
Cervical Cytology Service
Authors: A. Elliott
Journal: BMJ (1965)

MEDICAL JOURNAFor children in hospital we are amongst the pioneers in co-operating with hospital authorities to introduce play into the wards.The " play lady " does much to alleviate the fears and sense of insecurity attending going to hospital.Paediatric staff are beginning to discover that sick children absorbed in play recover more quickly and suffer less from the emotional upset sometimes following the hospital experience.-Iam, etc.,
Autoimmunity and antigenic targets in ovarian pathology
Authors: T. Forges
Journal: Human Reproduction Update (2004)

The involvement of autoimmune mechanisms in premature ovarian failure has been put forward by numerous investigators. In various other ovarian pathologies, such as idiopathic infertility, polycystic ovary syndrome, or endometriosis, similar mechanisms have been suggested. However, the exact role of autoimmunity in the pathophysiology of these diseases still remains controversial. The diagnosis of autoimmune ovarian disease relies on several clinical, biological and histological findings, but special interest has been focused on antiovarian autoantibodies. The search for these antibodies has been undertaken by several authors and yielded somewhat conflicting results which might be conditioned by methodological differences and by the multiplicity of potential immune targets. These targets, which comprise various steroidogenic enzymes, gonadotrophins and their receptors, the corpus luteum, zona pellucida and oocyte, are reviewed. Further investigation of these targets is required to improve the diagnostic tools that will lead to a precocious and reliable diagnosis of autoimmune ovarian disease, an appropriate clinical surveillance as well as the selection of patients who may benefit from immune‐modulating therapy and possibly recover ovarian function and fertility.
THE DYNAMICS OF RETICULOENDOTHELIAL BLOCKADE
Authors: M. Glenn Koenig, Robert M. Heyssel, M. Ann Melly, David E. Rogers
Journal: The Journal of Experimental Medicine (1965)

The dynamics of "reticuloendothelial blockade" were studied in living rabbits and isolated, perfused rabbit livers utilizing gelatin as a blockading agent and Au(198) stabilized in gelatin as a tracer. Employing the above experimental model, the following observations were made. (a) RES blockade was specific and dependent on the surface properties of the particle under study. (b) RES blockade was not caused by saturation of hepatic removal mechanisms. (c) RES blockade was not caused by depletion of demonstrable serum opsonins. (d) RES blockade appeared to correlate with high circulating levels of the blockading agent, per se. Thus, under the conditions employed, the term "reticuloendothelial blockade" was a misnomer. Although specificity of liver macrophage-particle interaction was evident and deserves further study, the data suggest that blockade as usually studied is a laboratory phenomenon induced by the continuing circulation of the blockading agent.
Trajectories of Recovery and Dysfunction after Acute Illness, with Implications for Clinical Trial Design
Authors: Theodore J. Iwashyna
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

studies (9, 10).Other antiviral treatments are scarce: ribavirin may be used in severe RSV and paramyxovirus infections, and cidofovir in adenovirus infections, particularly in immunocompromised hosts, but proof of efficacy remains elusive (11, 12).Drugs against rhinovirus and others are under development, but are not yet available (13).The treatment of patients having developed severe pneumonia with a specific antiviral treatment is thus far from becoming the standard of care, but this is now due to the lack of drugs and no longer to the lack of appropriate diagnostic procedures.In conclusion, undoubtedly viral infection of the respiratory tract may be associated with and/or cause exacerbation of chronic lung disease ( 14) or serious lower respiratory tract complications including viral pneumonia, and probably in a much larger proportion of patients than commonly thought, particularly if immunosuppression or other conditions are present (8).Choi and coauthors contribute to the knowledge and understanding of the etiology of severe pneumonia including HCAP.This could provide hints to design studies to limit antibiotic overuse (a key issue not addressed in the study) and to better control hospital transmission of viral agents.However, many unresolved questions still remain, the main one being the direct therapeutic consequences due to the absence of a specific antiviral agent for most of these infections.Progress in clinical microbiology has surpassed antiviral drug development, but the time has come for clinicians to use these diagnostic tools to impact their clinical management and to be prepared for future progress in the field.
Ten-Year Outcomes in a Population-Based Cohort of Node-Negative, Lymphatic, and Vascular Invasion–Negative Early Breast Cancers Without Adjuvant Systemic Therapies
Authors: Stephen K. Chia, Caroline H. Speers, Cicely J. Bryce, Malcolm M. Hayes, Ivo A. Olivotto
Journal: Journal of Clinical Oncology (2004)

To discuss the absolute benefits from adjuvant systemic therapy knowledge of long-term outcomes and baseline risks of relapse and disease-specific survival are required. We assessed the 10-year outcomes in a population-based cohort of node-negative (N-) lymphovascular negative (LV-) early breast cancers diagnosed from 1989 to 1991 who did not receive adjuvant systemic therapy.One thousand one hundred eighty-seven cases of pT(1-2)N(0) LV- breast cancers with a median follow-up of 10.4 years were reviewed. Kaplan-Meier survival curves for relapse free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS) were compared with log-rank tests with cohorts stratified for tumor size and grade.The median age of this series was 62 years. Four hundred thirty tumors were < or = 1 cm in diameter (cohort 1), 507 were 1.1-2 cm (cohort 2), and 250 were 2.1 to 5 cm in diameter (cohort 3). The 10-year outcomes for cohorts 1, 2, and 3, respectively, were significantly different: RFS, 82%, 75%, and 66%; BCSS, 92%, 90%, and 77%; and OS, 79%, 78%, and 66%. Tumor grade significantly altered outcome within size cohorts, particularly in pT(1)N(0) breast cancers.This study provides detailed information on the continued relapse and breast cancer death rate to 10 years of follow-up. Specifically, without adjuvant systemic therapy, patients with LV-, N - breast cancer had a > or = 25% 10-year risk of relapse and a corresponding 10-year breast cancer death rate of > or = 10% if they had either a grade 3 tumor < or = 1 cm, a grade 2 to 3 tumor from 1.1 to 2 cm, or any grade tumor greater than 2 cm.
Induction of Coxsackievirus-Adenovirus–Receptor Expression During Myocardial Tissue Formation and Remodeling
Authors: Henry Fechner, Michel Noutsias, Carsten Tschoepe, Kerstin Hinze, Xiaomin Wang, Felicitas Escher, Matthias Pauschinger, Dick Dekkers, Roland Vetter, Martin Paul, Jos Lamers, Heinz-Peter Schultheiss, Wolfgang Poller
Journal: Circulation (2003)

The coxsackievirus-adenovirus receptor (CAR) was cloned as a receptor for both viruses, but its primary biological functions and regulatory mechanisms are unknown. CAR was low in healthy adult myocardium, whereas strong CAR reexpression was observed in human dilated cardiomyopathy. The molecular mechanisms of CAR induction in cardiomyocytes are unknown.We report on CAR regulation during development, CAR induction after myocardial infarction, and cell-to-cell contact-dependent CAR regulation in the rat. The high CAR expression during development in various organs decreased up to 190-fold after birth. After infarction resulting in severe cardiac dysfunction (dP/dt(max), -53%; dP/dt(min), -58%; left ventricular pressure, -45%), CAR was induced locally in cardiomyocytes of the infarct zone, where it was also expressed by capillary-like CD31+ structures and CD18+ interstitial cells, whereas it remained confined to subendothelial layers of arterioles and venules. In cultured cardiomyocytes, endothelin-1, cardiotrophin-1, leukemia-inhibiting factor, and cyclic stretch had no effect on CAR, whereas at high versus low cell density, CAR was suppressed up to 10-fold (P=0.006). Conditioned media from low- or high-density cardiomyocytes or cardiofibroblasts had no effect.The locally confined CAR upregulation after infarction makes induction by various humoral factors unlikely, because cardiac dysfunction results in high activities of sympathetic and renin-angiotensin systems and cytokines. The cell culture experiments identify a cell-to-cell contact-dependent mechanism of CAR regulation. Further characterization of the signals linking cell-to-cell interactions to CAR gene expression may provide insight into mechanisms and functional consequences of the generalized CAR induction in dilated cardiomyopathy, and of its local induction after myocardial infarction.
Fibroblast Growth Factor-2 and Receptor-1α(IIIc) Regulate Postnatal Rat Lung Cell Apoptosis
Authors: Man Yi, Rosetta Belcastro, Samuel Shek, Daochun Luo, Martin Post, A. Keith Tanswell
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Fibroblast growth factor receptor-1alpha(IIIc) [FGF-R1alpha(IIIc)] regulates recovery of neonatal rat lung growth, after 95% oxygen-mediated growth arrest. Its role in normal postnatal alveologenesis is unknown.To determine if FGF-R1alpha(IIIc) regulates normal postnatal alveologenesis.Truncated soluble FGF-R1alpha(IIIc) or neutralizing antibodies to FGF-1 or FGF-2 were injected intraperitoneally into 3-d-old rats. The pups were killed at Day 7 for studies of alveolar development.Injected, truncated soluble FGF-R1alpha(IIIc) inhibited phosphorylation of the endogenous FGF-R1, and downstream pathway, and paradoxically increased lung DNA content and tissue fraction while inhibiting lung cell DNA synthesis. The increase in tissue thickness was due to reduced apoptosis, as indicated by reductions in cleaved effector caspases 3 and 7. Inhibition of the intrinsic apoptosis pathway was suggested by decreases in the proapoptotic protein Bax and mitochondrial cytochrome c release, and an increase in the antiapoptotic protein Bcl-x(L). Injected antibodies to FGF-1 and FGF-2 had no effect on DNA synthesis, but both increased Bcl-x(L) content and decreased cytochrome c release and cleaved caspase-7 protein expression. However, only injection of the antibody to FGF-2 replicated the increased tissue fraction and inhibited apoptosis observed with the injection of truncated soluble FGF-R1alpha(IIIc).Inhibition of ligand binding, most likely of FGF-2, to the FGF-R1alpha(IIIc) inhibits normal postnatal lung cell apoptosis.
Resistance to Lyme disease in decorin-deficient mice
Authors: Eric L. Brown, R. Mark Wooten, Barbara J.B. Johnson, Renato V. Iozzo, Amanda Smith, Marc C. Dolan, Betty P. Guo, Janis J. Weis, Magnus Höök
Journal: Journal of Clinical Investigation (2001)

Microbial adhesion to the host tissue represents an early, critical step in the pathogenesis of most infectious diseases. Borrelia burgdorferi, the causative agent of Lyme disease (LD), expresses two surface-exposed decorin-binding adhesins, DbpA and DbpB. A decorin-deficient (Dcn–/–) mouse was recently developed and found to have a relatively mild phenotype. We have now examined the process of experimental LD in Dcn–/– mice using both needle inoculation and tick transmission of spirochetes. When exposed to low doses of the infective agent, Dcn–/– mice had fewer Borrelia-positive cultures from most tissues analyzed than did Dcn+/+ or Dcn+/– mice. When the infection dose was increased, similar differences were not observed in most tissues but were seen in bacterial colonization of joints and the extent of Borrelia-induced arthritis. Quantitative PCR demonstrated that joints harvested from Dcn–/– mice had diminished Borrelia numbers compared with issues harvested from Dcn+/+ controls. Histological examination also revealed a low incidence and severity of arthritis in Dcn–/– mice. Conversely, no differences in the numbers of Borrelia-positive skin cultures were observed among the different genotypes regardless of the infection dose. These differences, which were observed regardless of genetic background of the mice (BALB/c or C3H/HeN) or method of infection, demonstrate the importance of decorin in the pathogenesis of LD.
CHANGES IN THE TITER OF ANTIPNEUMOCOCCAL HUMORAL IMMUNITY IN ADULT HUMAN BEINGS
Authors: James B. Graeser, M. Cornwell Harrison
Journal: The Journal of Experimental Medicine (1933)

Fifty-five individuals were tested to determine the pneumococcidal promoting activity of their serum against Types I and II pneumococci. By repeated tests an attempt was made to study the constancy of the degree of their immunity over intervals of 2 to 6 months. In this group were included nine persons with common colds and twelve cases of a severe influenza-like infection. Fifteen of the fifty-five cases showed a change in titer of their humoral immunity against either Type I or Type II or both. Three of these showed an increase, and twelve a decrease. This reaction in most instances was a specific one in that the altered reaction toward one type was not associated with a similar change toward the other type pneumococcus. Colds and influenza-like infections apparently exerted no effect upon the titer of humoral immune substances.
Oncogenic K-ras Drives Cell Cycle Progression and Phenotypic Conversion of Primary Pancreatic Duct Epithelial Cells
Authors: Cristina Agbunag, Dafna Bar-Sagi
Journal: Cancer Research (2004)

Abstract We have established a primary pancreatic duct epithelial cell culture (PDEC) system to investigate the relationship between oncogenic activation of K-ras and pancreatic ductal tumorigenesis. We have found that the acute introduction of physiological levels of oncogenic K-ras (K-rasV12) into quiescent PDECs stimulates S-phase entry and induces a pronounced increase in cell size. Both effects are dependent on the functional integrity of the phosphatidylinositol 3′-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway. In addition, K-rasV12 promotes the loss of epithelial E-cadherin and the gain of mesenchymal N-cadherin in PDEC. Our observations indicate that the oncogenic activation of K-ras is sufficient to elicit mitogenic and morphogenic responses in pancreatic ductal cells and hence is likely to play an instructive role in the initiation of pancreatic ductal adenocarcinoma.
Clinical results and revascularization status five years following randomization to PTCA or CABQ in bypass angioplasty revascularization investigation (BARI)
Authors: E.L. Aldermann, M.G. Bourassa, P.L. Whillow, R.M. Califf, L. Schwartz, K.E. Kip
Journal: Journal of the American College of Cardiology (1998)
The Consult Guys - Clean Coronaries But a Broken Heart
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2014)

Web Exclusives16 September 2014The Consult Guys - Clean Coronaries But a Broken HeartFREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MD and Howard H. Weitz, MDAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G14-3009 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Bayer, sanofi-aventis; Consultancies: Bristol-Myers Squibb, Bayer, sanofi-aventis. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 September 2014Volume 161, Issue 6Page: CG9KeywordsConflicts of interestHeartResearch grantsResearch reporting guidelines ePublished: 16 September 2014 Issue Published: 16 September 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.Loading ...
Recovery after taking Weedol
Authors: E. Li. Lloyd
Journal: BMJ (1969)

satisfactory therapeutic response.The total available evidence suggests that had lower degrees of prothrombin activity been consistently maintained the results might have more closely resembled those of the Anticoagulant Committee of the American Heart Association,2 Loeliger and his co-workers,' and Meuwissen and Hart,' Aspenstrbm and Korsan-Bengtsen,' and the results of the U.S. Veterans Administration Long-Term Study,' ' as well as many other studies both short-and long-term from the British Isles and from other countries.The Working Party of the Medical Research Council had previously used an average daily dose of 108 mg. of phenindione in their study dealing with long-term pre- ventive anticoagulant therapy, which pro- duced favourable effects in several important categories of mortality and morbidity.How- ever, in this study involving acute myocardial infarction the use of the Thrombotest at 10-20% levels resulted in a serious reduction of approximately one-third in the daily dose to an average of 72 mg.This represents a paradox in the principle of anticoagulant therapy.Acute thromboembolic states usually require more active rather than less active treatment when compared with long- term prevention in an otherwise quiescent phase.What this study does confirm is that when levels of activity in the range of 10-20% by the Thrombotest are used only minor therapeutic effects involving thrombo- embolic complications can be expected.As with all other potent drugs, one must give adequate amounts of anticoagulants to obtain full therapeutic effects.It is a matter of great and international concern that clinicians not especially con- versant with the problems and the research in this field will assume that the treatment was optimal, and thereby interpret this report as establishing that anticoagulants are ineffec- tive in the treatment of acute myocardial infarction.This conclusion is not warranted -the therapeutic level used was not optimal.
Manifestations of Concentration Camp Effects on the Second Generation
Authors: HARVEY A. BAROCAS, CAROL B. BAROCAS
Journal: American Journal of Psychiatry (1973)

The authors explore the process by which the concentration camp syndrome, which includes destructive self-identification, is perpetuated in the children of survivors in ways that engender depression, guilt, and aggression and inhibit autonomous growth. They point out the need for further research that will provide a clearer understanding of the dynamics involved and suggest treatment possibilities.
Intrinsic Factor-mediated Absorption of Cobalamin by Guinea Pig Ileal Cells
Authors: Cyrus R. Kapadia, Del Serfilippi, Kurt Voloshin, Robert M. Donaldson
Journal: Journal of Clinical Investigation (1983)

To investigate the fate of intrinsic factor and cobalamin during cobalamin absorption, we incubated enterocytes isolated from guinea pig ileum for periods of up to 30 min with 57Co-labeled cyano-cobalamin bound either to human intrinsic factor or to rabbit intrinsic factor biosynthetically labeled with [35S]methionine. When the labeled complex was incubated for 30 min with isolated ileal cells under conditions that block cellular metabolism, virtually all cellular radioactivity could be removed by washing the cell surface with EDTA or acid. In contrast, washing removed only half the radioactivity from cells incubated at 37°C in O2. When residual cellular radioactivity was extracted and analyzed by gel filtration, 80-94% of both the 35S and 57Co radioactivity eluted in the same fractions as the original complex. The remaining 6-20% eluted as free [57Co]cobalamin or [35S]methionine. To examine events occurring after 30 min, we instilled into tied-off ileal loops of intact guinea pigs radiolabeled intrinsic factor-cobalamin complex and extracted nondissociable radioactivity 2-4.5 h later. The proportion of extracted 57Co eluting as free cobalamin increased to 39-46%, that eluting as intrinsic factor-cobalamin complex declined to 22-45%, and 9-34% now eluted as a macromolecule that reacted with antitranscobalamin II antibody but not antiintrinsic factor antibody. Extracted 35S radioactivity eluted in several peaks in addition to the intrinsic factor peak. These findings suggest that (a) after reversible attachment of intrinsic factor-cobalamin complex to its ileal surface receptor, an energy-dependent process prevents removal of the complex from the cell surface by EDTA or acid; (b) cobalamin dissociates from intrinsic factor and, as suggested by previous workers, binds to a molecule antigenically similar to transcobalamin II; and (c) intrinsic factor is slowly degraded and forms breakdown products that are detectable in ileal extracts.