tbuckley/cabot-search huggingface dataset:
Modeling Sites of RNA Editing as a Fifth Nucleotide State Reveals Progressive Loss of Edited Sites from Angiosperm Mitochondria
Authors: Jeffrey P. Mower
Journal: Molecular Biology and Evolution (2007)

RNA editing is a type of nucleic acid modification found in many eukaryotic lineages. In plants, RNA editing occurs by the site-specific conversion of cytidines to uridines in mitochondrial and plastid transcripts. To quantify the rates of edit site gain and loss in angiosperm mitochondrial genes, a nonreversible maximum likelihood model was developed that treats sites of RNA editing as a fifth nucleotide state. The rate of loss of editing, either by genomic replacement with a thymidine or by loss of recognition by the editing complex, was found to be significantly higher than the rate of gain. Furthermore, the frequency of editing is not at equilibrium in angiosperm mitochondrial sequences; there is a strong tendency for the number of edited sites to decrease over time. These results indicate that selection plays a key role in driving the higher rate of edit site loss relative to gain and suggest that the strength of selection against editing has become increasingly stringent over the course of angiosperm evolution. The model described here should be easily adaptable to other systems that involve nucleic acid modifications.
Filaggrin null alleles are not associated with hand eczema or contact allergy
Authors: A. Lerbaek, H. Bisgaard, T. Agner, K. Ohm Kyvik, C.N.A. Palmer, T. Menné
Journal: British Journal of Dermatology (2007)

The filaggrin protein is a key component of stratum corneum and homo- or heterozygotes for the filaggrin variant alleles R501X and 2282del4 have varying degrees of impaired skin barrier. The variant alleles have repeatedly been shown to be associated with atopic dermatitis. Any possible association with hand eczema or contact allergy are unexplored.To explore associations between the variant alleles, hand eczema, contact allergy and atopic dermatitis.In total, 183 adult individuals participated in a clinical examination of the hands, patch testing and filaggrin genotyping. Children without any evidence of atopic dermatitis from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) study were used as controls. The chi(2) test was used for comparison of allele frequencies.The majority (73%) had hand eczema, 25% had contact allergy and 14% had a diagnosis of atopic dermatitis. The association between atopic dermatitis and the filaggrin variant alleles was confirmed (odds ratio 3.5, P = 0.015). Allele frequencies in individuals with hand eczema or contact allergy were not statistically significantly increased.There is no association between the variant alleles and hand eczema or contact allergy.
Minimally Invasive Surfactant Administration in Preterm Infants
Authors: Kiran More, Pankaj Sakhuja, Prakesh S. Shah
Journal: JAMA Pediatrics (2014)

IMPORTANCE Surfactant administration by minimally invasive methods that allow for spontaneous breathing might be safer and more effective than administration with endotracheal intubation and mechanical ventilation; however, the efficacy and safety of minimally invasive methods have not been reviewed.OBJECTIVE To conduct a meta-narrative review of the efficacy and safety of minimally invasive surfactant administration using a thin catheter, aerosolization, a laryngeal mask airway, and pharyngeal administration in preterm infants with or at risk for respiratory distress syndrome.
The painful heel. Comparative study in rheumatoid arthritis, ankylosing spondylitis, Reiter's syndrome, and generalized osteoarthrosis.
Authors: J C Gerster, T L Vischer, A Bennani, G H Fallet
Journal: Annals of the Rheumatic Diseases (1977)

This study presents the frequency of severe and mild talalgias in unselected, consecutive patients with rheumatoid arthritis, ankylosing spondylitis, Reiter's syndrome, and generalized osteoarthosis. Achilles tendinitis and plantar fasciitis caused a severe talalgia and they were observed mainly in males with Reiter's syndrome or ankylosing spondylitis. On the other hand, sub-Achilles bursitis more frequently affected women with rheumatoid arthritis and rarely gave rise to severe talalgias. The simple calcaneal spur was associated with generalized osteoarthrosis and its frequency increased with age. This condition was not related to talalgias. Finally, clinical and radiological involvement of the subtalar and midtarsal joints were observed mainly in rheumatoid arthritis and occasionally caused apes valgoplanus.
Adenovirus Type 12 Infection
Authors: Henry G. Cramblett, Elizabeth W. Edmond
Journal: JAMA (1964)

IN 1962, Trentin and others<sup>1</sup>reported that adenovirus type 12 produced undifferentiated sarcoma when injected into newborn hamsters after an interval of 33 days or more. This was the first report of malignancies produced in animals by inoculation of virus of human origin. Reports of recovery of this virus from specimens taken from ill children have been few. The prototype strain (Huie) was recovered from the stool specimen of a child with suspected nonparalytic poliomyelitis.<sup>2</sup>Further isolations have been made from the anal swabs of apparently well children.<sup>3,4</sup>Recent reports have described the recovery of this virus from specimens from children with central nervous system (CNS) disease<sup>5,6</sup>and illnesses resembling acute lymphocytosis.<sup>7</sup> This report describes illnesses of three infants and one child from whom adenovirus type 12 was recovered, the serologic responses of the patients to the infection, and studies of the incidence of neutralizing
Anticoagulants and Cerebral Embolism
Authors: Frederic Reichel
Journal: JAMA (1968)

<h3>To the Editor:—</h3> The use of anticoagulants in the management of cerebal embolism has been highly controversial, and after studying some of the literature, I have concluded that the evidence is contradictory to your editorial statement that therapy should probably be promptly instituted rather than waiting several days (<b>201</b>:877, 1967). The rationale for prompt use of anticoagulants is based primarily on the study of Carter,<sup>1</sup>in which he reported a significantly higher recovery rate in those patients who were promptly treated. Subsequent reports by other investigators were less enthusiastic however, and Carter himself has modified his earlier approach, delaying anticoagulants for three weeks.<sup>2</sup> Neuropathologists are familiar with the frequent occurrence of hemorrhagic infarction following cerebral embolism, as shown both in experimental animals and at autopsy. Fisher and Adams<sup>3</sup>reported a 51% incidence of hemorrhagic infarction in 123 cases of fatal cerebral embolism. They demonstrated fragmentation of
Mitochondria-targeted ubiquinone (MitoQ) decreases ethanol-dependent micro and macro hepatosteatosis
Authors: Balu K. Chacko, Anup Srivastava, Michelle S. Johnson, Gloria A. Benavides, Mi Jung Chang, Yaozu Ye, Nirag Jhala, Michael P. Murphy, Balaraman Kalyanaraman, Victor M. Darley-Usmar
Journal: Hepatology (2011)

Abstract: Chronic alcohol-induced liver disease results in inflammation, steatosis, and increased oxidative and nitrosative damage to the mitochondrion. We hypothesized that targeting an antioxidant to the mitochondria would prevent oxidative damage and attenuate the steatosis associated with alcoholic liver disease. To test this we investigated the effects of mitochondria-targeted ubiquinone (MitoQ) (5 and 25 mg/kg/day for 4 weeks) in male Sprague-Dawley rats consuming ethanol using the Lieber-DeCarli diet with pair-fed controls. Hepatic steatosis, 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), hypoxia inducible factor α (HIF1α), and the activity of the mitochondrial respiratory chain complexes were assessed. As reported previously, ethanol consumption resulted in hepatocyte ballooning, increased lipid accumulation in the form of micro and macrovesicular steatosis, and induction of cytochrome P450 2E1 (CYP2E1). MitoQ had a minor effect on the ethanol-dependent decrease in mitochondrial respiratory chain proteins and their activities; however, it did decrease hepatic steatosis in ethanol-consuming animals and prevented the ethanol-induced formation of 3-NT and 4-HNE. Interestingly, MitoQ completely blocked the increase in HIF1α in all ethanol-fed groups, which has previously been demonstrated in cell culture models and shown to be essential in ethanol-dependent hepatosteatosis. Conclusion: These results demonstrate the antioxidant capacity of MitoQ in alleviating alcohol-associated mitochondrial reactive oxygen species (ROS) and several downstream effects of ROS/RNS (reactive nitrogen species) production such as inhibiting protein nitration and protein aldehyde formation and specifically ROS-dependent HIF1α stabilization. (HEPATOLOGY 2011;)
Development of a Health-Protective Drinking Water Level for Perchlorate
Authors: David Ting, Robert A. Howd, Anna M. Fan, George V. Alexeeff
Journal: Environmental Health Perspectives (2006)

We evaluated animal and human toxicity data for perchlorate and identified reduction of thyroidal iodide uptake as the critical end point in the development of a health-protective drinking water level [also known as the public health goal (PHG)] for the chemical. This work was performed under the drinking water program of the Office of Environmental Health Hazard Assessment of the California Environmental Protection Agency. For dose-response characterization, we applied benchmark-dose modeling to human data and determined a point of departure (the 95% lower confidence limit for 5% inhibition of iodide uptake) of 0.0037 mg/kg/day. A PHG of 6 ppb was calculated by using an uncertainty factor of 10, a relative source contribution of 60%, and exposure assumptions specific to pregnant women. The California Department of Health Services will use the PHG, together with other considerations such as economic impact and engineering feasibility, to develop a California maximum contaminant level for perchlorate. We consider the PHG to be adequately protective of sensitive subpopulations, including pregnant women, their fetuses, infants, and people with hypothyroidism.
Signal Transduction Mechanisms of Ca<sup>2+</sup>Mobilizing Hormones: The Case of Gonadotropin-Releasing Hormone*
Authors: ZVI NAOR
Journal: Endocrine Reviews (1990)

Hormones, neurotransmitters, growth factors, antigens, and light exert their diverse biological effects by producing "second messenger" molecules which amplify and propagate the receptor signal into the cell biochemical network. The "second messengers" [e.g. cAMP, cGMP, Ca2+, and diacylglycerol (DG)] activate respective protein kinases which are the key enzymes in the regulatory network of the living organism (1). Protein kinases (∼100 have been described) are divided into serine/threonine and tyrosine-specific kinases (2). The main members of the first family are activated by second messengers, whereas several members of the tyrosine-specific kinases are associated with growth factor receptors or are encoded by retroviral oncogenes or the cellular homolog counterparts. The kinases catalyze the transfer of phosphate from ATP to serine, threonine, or tyrosine in the substrate proteins, and phosphatases remove the phosphate group (3). The phosphorylation-dephosphorylation cycle enables the cell to alternate from resting to activated state (or vice versa) according to the stimuli input.
Heat clearance and heat production studies in acute experimental coronary occlusion
Authors: J. GRAYSON, M. ROBERTSON, C. SCOTT
Journal: Cardiovascular Research (1973)

After acute coronary occlusion in the anaesthetized dog, heat clearance from a heated thermocouple declined slowly, whereas heat production fell abruptly, thereafter recovering slightly. Since heat clearance depends on total flow and heat production on nutritional or capillary flow, it is suggested that non-nutritional flow channels may exist in the myocardium.
β1A Integrin Expression Is Required for Type 1 Insulin-Like Growth Factor Receptor Mitogenic and Transforming Activities and Localization to Focal Contacts
Authors: Hira Lal Goel, Michael Breen, Jianzhong Zhang, Ishita Das, Sadie Aznavoorian-Cheshire, Norman M. Greenberg, Ada Elgavish, Lucia R. Languino
Journal: Cancer Research (2005)

The cells' ability to proliferate in response to growth factor stimulation is significantly altered during cancer progression. To investigate the mechanisms underlying these alterations in prostate cancer, the role and expression of beta1A integrin and type 1 insulin-like growth factor receptor (IGF-IR), known to contribute to cell proliferation and transformation, were analyzed. Using small interfering RNA oligonucleotides to down-regulate beta1A, we show that beta1A expression is required for IGF-IR-mediated prostate cancer cell proliferation and anchorage-independent growth. In vivo, using age-matched transgenic adenocarcinoma of mouse prostate (TRAMP) mice at different stages of prostate cancer [prostatic intraepithelial neoplasia, PIN; well-differentiated adenocarcinoma, WD; and poorly differentiated adenocarcinoma, PD], the expression of beta1A and of IGF-IR was studied. beta1A and IGF-IR expression levels were concurrently up-regulated in high PIN and WD, whereas their expression did not correlate in late-stage PD. In contrast to the up-regulated expression of beta1A, the levels of beta1C, a beta1 cytoplasmic variant that inhibits cell proliferation, were down-regulated in all stages of prostate cancer. A similar expression pattern was observed for a beta1C downstream effector, Grb2-associated binder-1 (Gab1) which is known to inhibit IGF-IR phosphorylation. To analyze in vitro the mechanistic implications of beta1A, beta1C, and Gab1 deregulation in prostate cancer, we investigated whether expression of either beta1 variant in beta1-null cells affected IGF-IR localization. We found that IGF-IR and beta1A were colocalized in highly specialized integrin signaling compartments, designated focal contacts. However, in the presence of beta1C, IGF-IR remained diffuse on the cell surface and did not localize to focal contacts. The findings that beta1 integrins and IGF-IR are concurrently deregulated and that expression of beta1 integrins is necessary to achieve appropriate IGF-IR intracellular distribution point to the important role that the cross-talk between these receptors may have during prostate cancer progression and will be helpful in formulating new therapeutic strategies.
Abstract 2985: CHD1L upregulates TCTP and induces mitotic defects and chromosome missegregation through decreasing Cdk1 activity by Cdc25C ubiquitination
Authors: Tim Hon Man Chan, Leilei Chen, Xin-Yuan Guan
Journal: Cancer Research (2011)

Abstract CHD1L is a target oncogene responsible for the 1q21 amplification event in hepatocellular carcinoma (HCC). Here, TCTP was found to be a CHD1L target gene. CHD1L protein directly binds to the promoter region (−733/-1027) of TCTP and upregulates the latter's expression in both cell lines and clinical specimens. Overexpression of TCTP, detected in 41.9% of human HCCs, was significantly associated with heavy liver cirrhosis and advanced tumor stage. During mitosis, the elevated expression of TCTP could accelerate the ubiquitin-proteasome degradation of Cdc25C, which in turn led to the failure in the dephosphorylation of Cdk1 on Tyr15 and the decreased Cdk1 activity, finally causing a faster mitosis exit and chromosome missegregation. Depletion experiments confirmed that TCTP accelerates M phase progression and induces tumorigenicity. Overall, we reveal a novel molecular pathway (CHD1L)-(TCTP)-(Cdc25C)-(Cdk1) during hepatocarcinogenesis which causes the malignant transformation of hepatocytes with the phenotypes of accelerated mitotic progression and the production of aneuploidy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2985. doi:10.1158/1538-7445.AM2011-2985
Duty to Warn Third Parties-Reply
Authors: Almeta E. Cooper
Journal: JAMA (1983)

<h3>In Reply.—</h3> The comments from attorney Brennan and Dr Biegler are appreciated. They illustrate the concern in both the medical and legal communities about the duty of physicians to warn third parties of the potentially violent behavior of their patients. Mr Brennan's comments about<i>McIntosh v Milano</i>are particularly helpful because the exoneration of the physician at the trial level helps demonstrate that the judicial system can respond appropriately to those who are able to document that their actions to warn or to refrain from warning others are based on a reasonable belief and evaluation of the individual patient.
Failure of atrial natriuretic factor to increase with saline load in patients with dilated cardiomyopathy and mild heart failure.
Authors: M Volpe, C Tritto, N De Luca, A F Mele, G Lembo, S Rubattu, M Romano, P De Campora, I Enea, B Ricciardelli
Journal: Journal of Clinical Investigation (1991)

To investigate whether the response of atrial natriuretic factor (ANF) to volume expansion is impaired in the early stages of dilated cardiomyopathy, the effects of saline load (SL; 0.25 ml/kg.min for 120 min) were assessed in 12 patients with dilated cardiomyopathy and asymptomatic to mildly symptomatic heart failure (HF) and in nine normal subjects (N). SL increased plasma ANF levels in N (from 14.3 +/- 2 to 19.5 +/- 3 and 26 +/- 4 pg/ml, at 60 and 120 min, respectively, P less than 0.001), but not in HF (from 42.9 +/- 9 to 45.9 +/- 9 and 43.9 +/- 8 pg/ml). Left ventricular end-diastolic volume (LVEDV) and stroke volume were increased (P less than 0.001) by SL in N but not in HF. Urinary sodium excretion (UNaV) increased in N more than in HF during SL, whereas forearm vascular resistance (FVR) did not change in N and increased in HF (P less than 0.001). In five HF patients SL was performed during ANF infusion (50 ng/kg, 5 ng/kg.min) that increased ANF levels from 37.1 +/- 10 to 146 +/- 22 pg/ml. In this group, SL raised both LVEDV (P less than 0.01) and ANF (P less than 0.05), whereas FVR did not rise. In addition, the UNaV increase and renin and aldosterone suppressions by SL were more marked than those observed in HF under control conditions. Thus, in patients with dilated cardiomyopathy and mild cardiac dysfunction, plasma ANF levels are not increased by volume expansion as observed in N. The lack of ANF response is related to the impaired cardiac adaptations. The absence of an adequate increase of ANF levels may contribute to the abnormal responses of HF patients to saline load.
TROPICAL CUTANEOUS MYIASIS IN MAN.
Authors: J. LEE ADAMS
Journal: JAMA (1904)

At the present time, when the construction of an isthmian canal has turned the attention of medical men toward the tropical diseases of the Isthmus of Panama, I believe it will be of both scientific and practical value to bring forward a few observations I made on the isthmus, in regard to one of the most troublesome and common diseases of that locality. Tropical cutaneous myiasis of man is caused by the<i>Dermatobia noxialis</i>, sometimes called the<i>Gusanotpeludo</i>or<i>Muche</i>. Since 1749 numerous authors have treated the subject, but usually from the entomologic standpoint. Among the authors may be mentioned Linnaeus,<sup>1</sup>Say,<sup>2</sup>Clark,<sup>3</sup>LeConte,<sup>2</sup>Verrill, Goudot, Matas, Blanchard,<sup>4</sup>Railliet,<sup>5</sup>and others.<sup>6</sup>Blanch ard's<sup>4</sup>article is the most extensive and complete. It contains a synopsis of the writings of thirty-one authors, extending from 1749 to 1889, and gives a detailed description of numerous larvae, which he has examined.
Uveitis in psoriasis associated with HLA-B51; a link to Behcet's disease?
Authors: E. Morita, S. Sato, S. Yamamoto
Journal: British Journal of Dermatology (1997)

Journal Article Uveitis in psoriasis associated with HLA‐B51; a link to Behcet's disease? Get access E. Morita, E. Morita Department of Dermatology, Hiroshima University School of Medicine, Kasumi 1‐2‐3, Minami‐ku, Hiroshima 734, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Sato, S. Sato Department of Dermatology, Hiroshima General Hospital, Jigozen 1‐3‐3, Hatsukaichi 738, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Yamamoto S. Yamamoto Department of Dermatology, Hiroshima University School of Medicine, Kasumi 1‐2‐3, Minami‐ku, Hiroshima 734, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 136, Issue 6, 1 June 1997, Page 979, https://doi.org/10.1111/j.1365-2133.1997.tb03957.x Published: 01 June 1997
Abstract 334: PIK3CA overexpression induces epithelial-mesenchymal transition and progression of head and neck squamous cell carcinonoma.
Authors: Li Du, Xi Chen, Jingping Shen, Fang Zhang, Shi-Long Lu
Journal: Cancer Research (2013)

Abstract Head and neck squamous cell carcinoma (HNSCC) patients have a poor prognosis and invasion and metastasis are the major causes of mortality. However, the molecular mechanisms of HNSCC invasion and metastasis remain obscure. The phosphatidylinositol 3-kinase (PI3K) pathway regulates a wide range of cellular processes crucial for tumorigenesis. Amplification and mutation of PIK3CA, the gene coding for the catalytic subunit of PI3K, are among the most common genetic alterations in human HNSCC. To delineate the in vivo roles of PIK3CA during head and neck tumorigenesis, we developed a PIK3CA genetically engineered mouse model (GEMM), in which PIK3CA overexpression is specifically induced in the head and neck epithelia. While overexpression of PIK3CA alone resulted in epithelial hyperplasia, and carcinoma in situ, it was not sufficient to induce visible tumor formation. In contrast, when we applied 4NQO, a DNA adduct-forming agent widely used as a tobacco surrogate together with PIK3CA overexpression, the PIK3CA-GEMM developed ∼50% poorly differentiated HNSCC compared to ∼10% of those in the control mice. PIK3CA tumors also had increased numbers of infiltrated leukocytes and angiogenesis. In addition, either regional lymph node metastases or lung metastases was observed in ∼40% of the PIK3CA-GEMM compared to no metastases in control mice. Characterizations of PIK3CA tumors revealed that PIK3CA tumors underwent epithelial and mesenchymal transition, and formed poorly differentiated metastatic tongue SCC in an orthotopical mouse model. Molecular analysis of the PIK3CA tumors suggests that rather than AKT, PDK1 facilitates progression of PI3K-driven HNSCC, and enhanced TGFbeta signaling with increased TGFbeta1 ligand and Smad3 may further contribute to this process. Lastly, overexpression of PIK3CA is associated with HNSCC progression and metastasis, and positively correlated with PDK1 expression but negatively with AKT activation, further verified the clinical relevance of our GEMM study. In summary, our results suggest that PIK3CA oncogene drives invasion and metastasis of HNSCC through PDK1 and TGFbeta signaling, and combined targeting of these pathways will reduce tumor progression in advanced HNSCC patients with PIK3CA alterations, which comprise about ∼40% of all HNSCC patients. Citation Format: Li Du, Xi Chen, Jingping Shen, Fang Zhang, Shi-Long Lu. PIK3CA overexpression induces epithelial-mesenchymal transition and progression of head and neck squamous cell carcinonoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 334. doi:10.1158/1538-7445.AM2013-334