tbuckley/cabot-search huggingface dataset:
Pulmonary toxoplasmosis in HIV-infected patients: usefulness of polymerase chain reaction and cell culture
Authors: I Lavrard, C Chouaid, P Roux, JL Poirot, M Marteau, B Lemarchand, MC Meyohas, JL Olivier
Journal: European Respiratory Journal (1995)

Toxoplasmosis is a serious opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). The lung is a major site of infection after the central nervous system. The aim of the study was to assess the polymerase chain reaction (PCR) and cell culture for the detection of Toxoplasma gondii. One hundred and thirty two human immunodeficiency virus (HIV)-infected patients with respiratory manifestations, who underwent fibreoptic bronchoalveolar lavage, were investigated. Detection of Toxoplasma gondii was compared using three techniques: Giemsa staining; polymerase chain reaction with specific primers derived from the P30 gene; and culture on the MRC5 cell line. Toxoplasma gondii was detected in the same four samples by all three techniques. We conclude that PCR adds little to conventional (and cheaper) tools already used to diagnose pulmonary toxoplasmosis.
Parathyroid Hormone–Related Protein Promotes Epithelial–Mesenchymal Transition
Authors: Juan Antonio Ardura, Sandra Rayego-Mateos, David Rámila, Marta Ruiz-Ortega, Pedro Esbrit
Journal: Journal of the American Society of Nephrology (2009)

Epithelial–mesenchymal transition (EMT) is an important process that contributes to renal fibrogenesis. TGF-β1 and EGF stimulate EMT. Recent studies suggested that parathyroid hormone–related protein (PTHrP) promotes fibrogenesis in the damaged kidney, apparently dependent on its interaction with vascular endothelial growth factor (VEGF), but whether it also interacts with TGF-β and EGF to modulate EMT is unknown. Here, PTHrP(1-36) increased TGF-β1 in cultured tubuloepithelial cells and TGF-β blockade inhibited PTHrP-induced EMT-related changes, including upregulation of α-smooth muscle actin and integrin-linked kinase, nuclear translocation of Snail, and downregulation of E-cadherin and zonula occludens-1. PTHrP(1-36) also induced EGF receptor (EGFR) activation; inhibition of protein kinase C and metalloproteases abrogated this activation. Inhibition of EGFR activation abolished these EMT-related changes, the activation of ERK1/2, and upregulation of TGF-β1 and VEGF by PTHrP(1-36). Moreover, inhibition of ERK1/2 blocked EMT induced by either PTHrP(1-36), TGF-β1, EGF, or VEGF. In vivo, obstruction of mouse kidneys led to changes consistent with EMT and upregulation of TGF-β1 mRNA, p-EGFR protein, and PTHrP. Taken together, these data suggest that PTHrP, TGF-β, EGF, and VEGF might cooperate through activation of ERK1/2 to induce EMT in renal tubuloepithelial cells.
Molecular pathogenesis of pediatric astrocytic tumors1
Authors: Mitsutoshi Nakamura, Keiji Shimada, Eiwa Ishida, Tomonori Higuchi, Hiroyuki Nakase, Toshisuke Sakaki, Noboru Konishi
Journal: Neuro-Oncology (2007)

Astrocytomas are the most common pediatric brain tumors, accounting for 7%-8% of all childhood cancers. Relatively few studies have been performed on their molecular properties; therefore, classification of pediatric astrocytic tumors into genetic subtypes similar to that of adult tumors remains to be defined. Here, we report an extensive characterization of 44 pediatric astrocytomas--16 diffuse astrocytomas (WHO grade II), 10 anaplastic astrocytomas (WHO grade III), and 18 glioblastomas (WHO grade IV)--in terms of genetic alterations frequently observed in adult astrocytomas. Some form of p53 mutation was found in three diffuse astrocytomas, in three anaplastic astrocytomas, and in six glioblastomas examined; PTEN mutations were detected only in two glioblastomas. EGFR amplification was detected in only one anaplastic astrocytoma and two glioblastomas, but no amplification was observed for the PDGFR-alpha gene. Loss of heterozygosity (LOH) on 1p/19q and 10p/10q was less common in pediatric astrocytic tumors than in those seen in adults, but the frequency of LOH on 22q was comparable, occurring in 44% of diffuse astrocytomas, 40% of anaplastic astrocytomas, and 61% of glioblastomas. Interestingly, a higher frequency of p53 mutations and LOH on 19q and 22q in tumors from children six or more years of age at diagnosis was found, compared with those from younger children. Our results suggest some differences in children compared to adults in the genetic pathways leading to the formation of de novo astrocytic tumors. In addition, this study suggests potentially distinct developmental pathways in younger versus older children.
TCT-56 Incremental value of platelet reactivity over a risk score of clinical and procedural variables in predicting bleeding events after percutaneous coronary intervention
Authors: Fabio Mangiacapra, Elisabetta Ricottini, Emanuele Barbato, Giuseppe Patti, Vincenzo Vizzi, Andrea D'Ambrosio, Bernard De Bruyne, William Wijns, Germano Di Sciascio
Journal: Journal of the American College of Cardiology (2012)
Murine cytotoxic T lymphocyte recognition of individual influenza virus proteins. High frequency of nonresponder MHC class I alleles.
Authors: J R Bennink, J W Yewdell
Journal: The Journal of Experimental Medicine (1988)

We determined the MHC restriction of CTL responses to five individual influenza virus proteins. Four viral proteins failed to be recognized in conjunction with three of the five class I alleles of the H-2k and H-2d haplotypes, while the fifth was recognized only in conjunction with a single allele. This indicates that there is a significant chance that a given class I allele will be associated with low responsiveness or nonresponsiveness for a given foreign protein. This explains, at least in part, why MHC-linked nonresponsiveness is frequently detected in polyclonal antiviral CTL responses. Most importantly, these findings support the idea that responsiveness to foreign antigens is a critical factor in maintaining the high degree of MHC class I polymorphism in outbred populations.
RORα Suppresses Breast Tumor Invasion by Inducing SEMA3F Expression
Authors: Gaofeng Xiong, Chi Wang, B. Mark Evers, Binhua P. Zhou, Ren Xu
Journal: Cancer Research (2012)

Inactivation of tumor suppressors and inhibitory microenvironmental factors is necessary for breast cancer invasion; therefore, identifying those suppressors and factors is crucial not only to advancing our knowledge of breast cancer, but also to discovering potential therapeutic targets. By analyzing gene expression profiles of polarized and disorganized human mammary epithelial cells in a physiologically relevant three-dimensional (3D) culture system, we identified retinoid orphan nuclear receptor alpha (RORα) as a transcription regulator of semaphorin 3F (SEMA3F), a suppressive microenvironmental factor. We showed that expression of RORα was downregulated in human breast cancer tissue and cell lines, and that reduced mRNA levels of RORα and SEMA3F correlated with poor prognosis. Restoring RORα expression reprogrammed breast cancer cells to form noninvasiveness structures in 3D culture and inhibited tumor growth in nude mice, accompanied by enhanced SEMA3F expression. Inactivation of RORα in nonmalignant human mammary epithelial cells inhibited SEMA3F transcription and impaired polarized acinar morphogenesis. Using chromatin immunoprecipitation and luciferase reporter assays, we showed that transcription of SEMA3F is directly regulated by RORα. Knockdown of SEMA3F in RORα-expressing cancer cells rescued the aggressive 3D phenotypes and tumor invasion. These findings indicate that RORα is a potential tumor suppressor and inhibits tumor invasion by inducing suppressive cell microenvironment.
Predictive implications of stress testing. Follow-up of 2700 subjects after maximum treadmill stress testing.
Authors: M H Ellestad, M K Wan
Journal: Circulation (1975)

Follow-up data on 2700 subjects who had had maximum stress tests were assembled in life tables. A positive test, characterized by ST-segment depression of 1.5 mm, 0.08 sec from the J point, predicted an incidence of some new coronary event of 9.5% a year, as compared with 1.7% in those with a negative test. The incidence of infarction and death was also significantly higher than in the negative responders. Early onset of ischemia occurring at moderate exercise (4 metabolic equivalents-METS) resulted in an incidence of all coronary events of 15% a year, while ischemia first manifested at the seventh minute of exercise (approximately 8 METS) results in an incidence of only 4% per year. The magnitude of ST depression and the age of onset of ischemia failed to influence the incidence of coronary events. A myocardial infarction previous to the test increased the incidence of events in both positive and negative responders. The positives with a previous infarction had more than double the incidence of coronary events than the positive responders with no pre-existing infarction. Those with chronotropic incompetence had a high incidence of coronary events even though the ECG response to exercise was normal.
Deletion polymorphism in the angiotensin I converting enzyme (ACE) gene as a genetic risk factor for sarcoidosis.
Authors: K. Furuya, E. Yamaguchi, A. Itoh, N. Hizawa, N. Ohnuma, J. Kojima, N. Kodama, Y. Kawakami
Journal: Thorax (1996)

BACKGROUND: Genetic control of serum angiotensin I converting enzyme (SACE) levels has been suggested. A study was undertaken to elucidate the role of this polymorphism in sarcoidosis. METHODS: Three hundred and forty one unrelated healthy controls and 103 consecutive patients with sarcoidosis participated in the study. SACE levels and an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene were studied in each subject and new reference intervals for SACE activity for each genotype were determined. The difference in genotype and allele frequencies between controls and patients was analysed and odds ratios were calculated to estimate the relative risk. RESULTS: A significant association was seen between ACE gene polymorphism and SACE levels in both patients and controls. The new reference intervals for each genotype discriminated abnormal SACE levels in patients more accurately, especially those with genotype II. In women the frequencies of allele I were 0.68 (allele D 0.32) in controls and 0.58 (allele D 0.42) in patients, and the difference between the two female groups was significant (p &lt; 0.05). Thus, an excess of genotype ID or DD was observed in female patients (odds ratio 2.18; 95% confidence interval 1.18 to 4.01; p = 0.01). CONCLUSIONS: These findings suggest that ACE gene polymorphism is associated with SACE levels in both patients with sarcoidosis and controls. ACE gene polymorphism should be further evaluated as a candidate marker for an increased risk of sarcoidosis.
Inverse relationship between net electric charge on the antigen and that on the sensitized cell in cellular immune response: demonstration with basic encephalitogen of the brain.
Authors: D Teitelbaum, C Webb, H Rauch, Y Karniely, R Arnon, M Sela
Journal: The Journal of Experimental Medicine (1975)

An inverse relationship exists between the net-electrical charge of immunogens and the antibodies elicited (1). The cellular basis of the net charge phenomenon has been established for both positively and negatively charged immunogens, by cell separation techniques over columns of opposite charge (7, 8). To establish whether this phenomenon can be extended to include cell-mediated immunity, the response to basic encephalitogenic protein (BE) which induces experimental allergic encephalomyelitis (EAE) was now investigated. Lymph node cells from sensitized strain 13 guinea pigs were fractionated over positively and negatively charged columns and compared to unfractionated cell populations in two assay systems: (a) in vitro response to BE in terms of lymphocyte transformation and (b) the passive transfer of EAE to unsensitized syngeneic recipients. The response was found to be confined to the fraction of cells eluted from glass bead columns, namely, the more negative cells. Cells eluted from poly-L-lysine-coated glass bead columns (i.e., positive cells) were devoid of the capacity to respond to this antigen either in vivo or in vitro. It was previously established that thymocytes rather than bone marrow cells account for the inverse charge phenomenon as assayed by T-helper-cell function in in vivo antibody production (8). We have now extended the inverse charge effect to include cell-mediated immune response of the delayed hypersensitivity type.
Re-epithelialization rate and protein expression in the suction-induced wound model: comparison between intact blisters, open wounds and calcipotriol-pretreated open wounds
Authors: T. Leivo, U. Kiistala, M. Vesterinen, K. Owaribe, R.E. Burgeson, I. Virtanen, A. Oikarinen
Journal: British Journal of Dermatology (2000)

We have investigated re-epithelialization following induction of suction blisters in humans in intact blisters, open wounds, i.e. blister roofs removed immediately after blister induction, and calcipotriol-pretreated open wounds. Intact blisters simulate blister healing in bullous disease, while open wounds simulate re-epithelialization during wound healing. Re-epithelialization was clearly faster in open wounds than in intact blisters, and was not affected by calcipotriol pretreatment. Bullous pemphigoid antigen 2 (BP180), bullous pemphigoid antigen 1 (BP230), plectin/hemidesmosomal 1 protein (HD1), laminin 5, laminin alpha5, laminin beta1, type VII collagen, tenascin-C, beta4, alphavbeta5, alpha5 and alpha9 integrins were studied in intact blisters and open wounds by immunohistochemistry. Hemidesmosomal plaque proteins BP230 and plectin/HD1, which connect the keratin cytoskeleton to the hemidesmosome, appeared earlier at the leading edge in intact blisters than in open wounds. Band-like immunostaining in the basement membrane for laminin 5, alpha5 and beta1 chains was continuous in blister bases, but partially discontinuous in open wound bases. The other antigens studied showed similar expression in intact blisters and open wounds. BP180, BP230, plectin/HD1, beta4 integrin, laminin 5 and tenascin-C expression were further studied in calcipotriol-pretreated open wounds. Calcipotriol did not affect the expression of these antigens. The immunohistochemical results suggest that the keratin cytoskeleton is linked to the basal plasma membrane of migrating basal cells via BP230 and plectin/HD1 earlier in the more slowly re-epithelializing blisters than in open wounds. An intact laminin sheath may inhibit keratinocyte migration in intact blisters.
The role of developmental immaturity and plasticity in evolution
Authors: David F. Bjorklund, Jason Grotuss
Journal: Behavioral and Brain Sciences (2006)

Aspects of cognitive immaturity may serve both to adapt children to their immediate environment and to prepare them for future ones. Language may have evolved in children's groups in the context of play. Developmental plasticity provides variability upon which natural selection operates, and such plasticity, that likely played an important role in the evolution of language, characterizes human children today.
Avenin fails to induce a Th1 response in coeliac tissue following in vitro culture
Authors: C Kilmartin
Journal: Gut (2002)

<b>Background:</b> It is well established that the wheat protein gliadin triggers inflammation in coeliac patients. However, the potential toxicity of avenin, the equivalent protein in oats, is debated. <b>Aim:</b> To investigate the immunogenicity of avenin using the cytokines interferon γ (IFN-γ) and interleukin (IL)-2 as markers of immunological activity. <b>Methods:</b> Duodenal biopsies from coeliac patients were cultured with 5 mg/ml of peptic tryptic (PT) gliadin (n=9) or 5 mg/ml of PT avenin (n=8) for four hours. Biopsies cultured with RPMI 1640 alone served as controls. Non-coeliac biopsies were also cultured with PT gliadin (n=8) and PT avenin (n=8). Total RNA was extracted from the tissue after culture. Cytokine mRNA was quantified by TaqMan polymerase chain reaction. Secreted cytokine protein was measured in the culture supernatant by enzyme linked immunosorbent assay. <b>Results:</b> After culture with PT gliadin, an increase in IFN-γ mRNA was observed in all nine patients with coeliac disease. Increased IFN-γ protein was also found in four of these patients. Smaller increases in IL-2 mRNA were detected in six subjects with increased IL-2 protein found in two patients. In contrast with PT gliadin, there was no significant IFN-γ or IL-2 response when coeliac biopsies were cultured with PT avenin. Similarly, biopsies from normal controls did not respond to PT gliadin or PT avenin stimulation. <b>Conclusions:</b> The findings of this study suggest that the immunogenic sequences in gliadin are not present in avenin. Moreover, they are in keeping with in vivo studies which report that oats are safe for consumption by coeliac patients.
Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro.
Authors: R S Kornbluth, P S Oh, J R Munis, P H Cleveland, D D Richman
Journal: The Journal of Experimental Medicine (1989)

To determine the effects of immunomodulatory agents upon HIV replication in macrophages, cultured monocyte-derived macrophages were treated with various substances and then infected with a macrophage-tropic strain of HIV-1. Pretreatment with rIFN-alpha, IFN-beta, and IFN-gamma, or bacterial LPS prevented viral replication in macrophages. In treated cultures, little or no infectious HIV or p24 core antigen was released into the supernatant, no virions were seen by electron microscopy, no viral RNA or DNA was detectable in the cell lysates, and no cytopathology (as determined by multinucleated giant cell formation) occurred. In contrast, pretreatment with a wide dose range of recombinant IL-1 beta, IL-2, IL-4, IL-6, M-CSF, TNF, or lymphotoxin failed to protect macrophages from productive infection by HIV. A consistent effect of granulocyte/macrophage-CSF on HIV replication in macrophages was not observed. In dose response studies, pretreatment with approximately 100 U/ml of IFN-alpha, approximately 10 U/ml of IFN-beta, or approximately 100 U/ml of IFN-gamma was sufficient to prevent virion release maximally and to prevent cytopathology completely. In kinetic studies, IFN-alpha, IFN-gamma, or LPS were added to the macrophage cultures either before or after infection with HIV. Even when added 3 d after infection with a multiplicity of 1 50% tissue-culture infectious dose per cell, all three treatments markedly reduced virion release, suggesting that these agents act at a point in the viral life cycle beyond the early events of virus binding, penetration, and uncoating. These data indicate that HIV replication in previously uninfected macrophages may be regulated by an inducible host cell mechanism. These findings may explain the restricted replication of HIV in macrophages in vivo and suggest an antiviral role for interferons in the therapy of HIV infection.
Temporal scaling of molecular evolution in primates and other mammals.
Authors: P D Gingerich
Journal: Molecular Biology and Evolution (1986)

Molecular clocks are routinely tested for linearity using a relative rate test and routinely calibrated against the geological time scale using a single or average paleontologically determined time of divergence between living taxa. The relative rate test is a test of parallel rate equality, not a test of rate constancy. Temporal scaling provides a test of rates, where scaling coefficients of 1.0 (isochrony) represent stochastic rate constancy. The fossil record of primates and other mammals is now known in sufficient detail to provide several independent divergence times for major taxonomic groups. Molecular difference should scale negatively or isochronically (scaling coefficients less than 1.0) with divergence time: where two or more divergence times are available, molecular difference appears to scale positively (scaling coefficient greater than 1.0). A minimum of four divergence times are required for adequate statistical power in testing the linear model: scaling is significantly nonlinear and positive in six of 11 published investigations meeting this criterion. All groups studied show some slowdown in rates of molecular change over Cenozoic time. The break from constant or increasing rates during the Mesozoic to decreasing rates during the Cenozoic appears to coincide with extraordinary diversification of placental mammals at the beginning of this era. High rates of selectively neutral molecular change may be concentrated in such discrete events of evolutionary diversification.
Laparoscopic Therapy of Cholelithiasis
Authors: J L Ponsky
Journal: Annual Review of Medicine (1993)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Children's facial expressions of pain in the context of complex social interactions
Authors: Carl L. von Baeyer
Journal: Behavioral and Brain Sciences (2002)

In children experiencing pain, the study of the social context of facial expressions might help to evaluate evolutionary and conditioning hypotheses of behavioural development. Social motivations and influences may be complex, as seen in studies of children having their ears pierced, and in studies of everyday pain in children. A study of opposing predictions of the long-term effects of parental caregiving is suggested.
Ikaros is absolutely required for pre-B cell differentiation by attenuating IL-7 signals
Authors: Beate Heizmann, Philippe Kastner, Susan Chan
Journal: The Journal of Experimental Medicine (2013)

Pre-B cell receptor (pre-BCR) signaling and migration from IL-7–rich environments cooperate to drive pre-B cell differentiation via transcriptional programs that remain unclear. We show that the Ikaros transcription factor is required for the differentiation of large pre-B to small pre-B cells. Mice deleted for Ikaros in pro/pre-B cells show a complete block of differentiation at the fraction C′ stage, and Ikaros-null pre-B cells cannot differentiate upon withdrawal of IL-7 in vitro. Restoration of Ikaros function rescues pre-B cell differentiation in vitro and in vivo and depends on DNA binding. Ikaros is required for the down-regulation of the pre-BCR, Igκ germline transcription, and Ig L chain recombination. Furthermore, Ikaros antagonizes the IL-7–dependent regulation of &amp;gt;3,000 genes, many of which are up- or down-regulated between fractions C′ and D. Affected genes include those important for survival, metabolism, B cell signaling, and function, as well as transcriptional regulators like Ebf1, Pax5, and the Foxo1 family. Our data thus identify Ikaros as a central regulator of IL-7 signaling and pre-B cell development.