tbuckley/cabot-search huggingface dataset:
Abstract B49: Integrin alpha2beta1 (α2β1) promotes prostate cancer skeletal metastasis
Authors: Joseph L. Sottnik, Stephanie Daignault-Newton, Xiaotun Zhang, Morrissey Colm, Maha H. Hussain, Evan T. Keller, Christopher L. Hall
Journal: Cancer Research (2013)

Abstract Men who die of prostate cancer (PCa) do so because of systemic metastases, the most frequent of which are within the skeleton. Recent data suggest that the colonization of the skeleton is mediated in part by collagen type I, the most abundant protein within the bone. We have shown that enhanced collagen I binding through increased expression of integrin α2β1 stimulated in vitro invasion and promoted the growth of PCa cells within the bone. Accordingly, we tested whether α2β1 integrin is both a mediator and a predictive marker of skeletal metastasis. To directly test whether α2β1 integrin expression mediates PCa cell metastasis, α2 integrin was over-expressed in low-tumorigenic LNCaP PCa cells or selectively knocked-down in highly metastatic LNCaPcol PCa cells. The over-expression of full-length cDNA to α2 integrin stimulated whereas shRNA-mediated knock-down of α2 integrin abolished the ability of transduced cells to bind to or migrate towards collagen I. Correspondingly, α2 integrin knock-down reduced both the tumor volume of intra-osseous lesions and the formation of experimental metastases in the liver and skeleton compared to control-transduced cells demonstrating that α2β1 promotes the establishment of distant metastases. To investigate the clinical significance of α2β1 expression in PCa, α2β1 protein was measured in prostatic tissues and in soft tissue and bone metastases. The data demonstrate that α2β1 protein was elevated in PCa skeletal metastases compared to either PCa primary lesions or soft tissue metastases suggesting that α2β1 mediates the selective metastasis of PCa cells to the bone. Taken together, these data support that α2β1 integrin promotes the systemic metastasis of PCa cells and provide evidence that α2β1 integrin activity may promote skeletal metastasis in PCa patients. These studies provide a strong rationale for the development of α2β1 as a therapeutic target for the treatment of PCa skeletal metastases and thus have the potential to reduce both the incidence and mortality associated with metastatic PCa. Citation Format: Joseph L. Sottnik, Stephanie Daignault-Newton, Xiaotun Zhang, Morrissey Colm, Maha H. Hussain, Evan T. Keller, Christopher L. Hall. Integrin alpha2beta1 (α2β1) promotes prostate cancer skeletal metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B49.
Orthostatic Tremor, Progressive External Ophthalmoplegia, and Twinkle
Authors: Margherita Milone, Bryan T. Klassen, Megan L. Landsverk, Richard H. Haas, Lee-Jun Wong
Journal: JAMA Neurology (2013)

Orthostatic tremor (OT) is a high-frequency (13-18 Hz) leg tremor occurring in standing position. Orthostatic tremor has an unknown pathophysiologic mechanism. It is thought to be sporadic but siblings with OT from 3 unrelated families were reported. No mutations have been reported in OT. We describe a patient with OT carrying a C10orf2 TWINKLE mutation to highlight the possible association of OT with mitochondrial dysfunction and mutations in the mitochondrial replicative helicase Twinkle.A man in his late 60s had ptosis and tremor on standing for 30 years, followed by development of progressive external ophthalmoplegia. Polygraphic recordings revealed an orthostatic synchronic tremor with 17.5-Hz frequency. Electromyography/nerve conduction studies showed evidence for a mild myopathy and associated mild axonal sensorimotor peripheral neuropathy. Muscle biopsy revealed ragged red fibers; mild cerebral atrophy was evident by magnetic resonance imaging. Molecular analysis revealed a novel heterozygous missense mutation at an evolutionarily conserved residue of the C10orf2 TWINKLE gene.Although the incidental association of OT and C10orf2 TWINKLE mutation is possible, the simultaneous onset of OT and eyelid ptosis at a much younger age than usually observed for OT raises the possibility of mitochondrial dysfunction and loss of mitochondrial DNA integrity in the pathogenesis of OT.
Pim Kinases Promote Cell Cycle Progression by Phosphorylating and Down-regulating p27Kip1 at the Transcriptional and Posttranscriptional Levels
Authors: Daisuke Morishita, Ryohei Katayama, Kazuhisa Sekimizu, Takashi Tsuruo, Naoya Fujita
Journal: Cancer Research (2008)

Abstract The serine/threonine kinase Pim is known to promote cell cycle progression and to inhibit apoptosis leading to tumorigenesis. However, the precise mechanisms remain unclear. We show, herein, that all the Pim family members (Pim1, Pim2, and Pim3) bind to and directly phosphorylate the cyclin-dependent kinase inhibitor p27Kip1 at threonine-157 and threonine-198 residues in cells and in vitro. The Pim-mediated phosphorylation induced p27Kip1 binding to 14-3-3 protein, resulting in its nuclear export and proteasome-dependent degradation. Ectopic expression of Pim kinases overcome the G1 arrest mediated by wild-type p27Kip1 but not by phosphorylation-resistant T157A-p27Kip1 or T198A-p27Kip1. In addition to the posttranslational regulations, p27Kip1 promoter assay revealed that Pim kinases also had the ability to suppress p27Kip1 transcription. Pim-mediated phosphorylation and inactivation of forkhead transcription factors, FoxO1a and FoxO3a, was involved in the transcriptional repression of the p27Kip1 gene. In contrast, inhibition of Pim signaling by expressing the dominant-negative form of Pim1 increased nuclear p27Kip1 level and attenuated cell proliferation. Because the CDK inhibitor p27Kip1 plays a crucial role in tumor suppression by inhibiting abnormal cell cycle progression, Pim kinases promote cell cycle progression and tumorigenesis by down-regulating p27Kip1 expression at both transcriptional and posttranslational levels. [Cancer Res 2008;68(13):5076–85]
Interleukin 8 secretion by colonic crypt cells in vitro: response to injury suppressed by butyrate and enhanced in inflammatory bowel disease.
Authors: P Gibson, O Rosella
Journal: Gut (1995)

Epithelia from several sites exhibit inducible secretion of interleukin 8 (IL-8). This study aimed to characterise secretion of IL-8 by colonic epithelial cells in vitro. Colonic crypt cells were isolated enzymatically from resected colon and the IL-8 content of culture supernates was measured by ELISA. The rate of secretion of IL-8 accelerated and levels of IL-8 transcripts increased appreciably during culture. Exposure to tumour necrosis factor alpha (TNF alpha) failed to increase secretion further. Secretion was not induced by the enzymatic digestion or by serum used in the culture medium but was significantly inhibited by butyrate, by a mean of 23%. Control experiments indicated that colonic crypt cells were the likely source. The secretion of IL-8 over 24 hours by cells from uninflamed mucosa of patients with ulcerative colitis or Crohn9s disease was more than twofold that from normal cells, while that from cancer bearing colons was normal. TNF alpha (10 mM) significantly suppressed IL-8 secretion only in the ulcerative colitis group and the change was different to those in the normal (p = 0.007) and Crohn9s disease groups (p = 0.012). Cells from inflamed areas secreted more IL-8 than those from autologous uninflamed areas (p = 0.009) but responses to modulating factors were no different. The induction of IL-8 secretion by colonic crypt cells in vitro is probably a response to injury associated with isolation and culture. It is suppressed by butyrate and increased in inflammatory bowel disease independently of the presence of mucosal inflammation. Whether epithelial derived IL-8 plays a part in the pathogenesis of inflammatory bowel disease is not yet clear.
‘Double trouble’: diagnostic challenges in genetic skin disorders
Authors: D. Kiritsi, M. Valari, K. Mileounis, L. Bruckner-Tuderman, C. Has
Journal: British Journal of Dermatology (2014)

Journal Article ‘Double trouble’: diagnostic challenges in genetic skin disorders Get access D. Kiritsi, D. Kiritsi Department of Dermatology Medical Center‐University of Freiburg Hauptstraße 7 79104 Freiburg Germany Search for other works by this author on: Oxford Academic Google Scholar M. Valari, M. Valari Department of Dermatology Agia Sofia Children's Hospital Athens Greece Search for other works by this author on: Oxford Academic Google Scholar K. Mileounis, K. Mileounis Private Dermatology Practice Palaio Faliro Athens Greece Search for other works by this author on: Oxford Academic Google Scholar L. Bruckner‐Tuderman, L. Bruckner‐Tuderman Department of Dermatology Medical Center‐University of Freiburg Hauptstraße 7 79104 Freiburg Germany Search for other works by this author on: Oxford Academic Google Scholar C. Has C. Has Department of Dermatology Medical Center‐University of Freiburg Hauptstraße 7 79104 Freiburg Germany Correspondence: Cristina Has. E‐mail: cristina.has@uniklinik-freiburg.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 1, 1 January 2015, Pages 276–278, https://doi.org/10.1111/bjd.13159 Published: 01 January 2015
Repression of 15-Hydroxyprostaglandin Dehydrogenase Involves Histone Deacetylase 2 and Snail in Colorectal Cancer
Authors: Michael G. Backlund, Jason R. Mann, Vijaykumar R. Holla, Qiong Shi, Takikoku Daikoku, Sudhansu K. Dey, Raymond N. DuBois
Journal: Cancer Research (2008)

Abstract Prostaglandin E2 (PGE2) promotes cancer progression by modulating proliferation, apoptosis, angiogenesis, and the immune response. Enzymatic degradation of PGE2 involves the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Recent reports have shown a marked diminution of 15-PGDH expression in colorectal carcinomas (CRC). We report here that treatment of CRC cells with histone deacetylase (HDAC) inhibitors, including sodium butyrate and valproic acid, induces 15-PGDH expression. Additionally, we show that pretreatment of CRC cells with HDAC inhibitors can block epidermal growth factor–mediated or Snail-mediated transcriptional repression of 15-PGDH. We show an interaction between Snail and HDAC2 and the binding of HDAC2 to the 15-PGDH promoter. In vivo, we observe increased Hdac2 expression in Apc-deficient mouse adenomas, which inversely correlated with loss of 15-Pgdh expression. Finally, in human colon cancers, elevated HDAC expression correlated with down-regulation of 15-PGDH. These data suggest that class I HDACs, specifically HDAC2, and the transcriptional repressor Snail play a central role in the suppression of 15-PGDH expression. These results also provide a cyclooxygenase-2–independent mechanism to explain increased PGE2 levels that contribute to progression of CRC. [Cancer Res 2008;68(22):9331–7]
1118-82 Distinct modes of cardiovascular death associated with impaired epicardial and myocardial perfusion following fibrinolysis for ST elevation myocardial infarction
Authors: Stephen D Wiviott, Marc S Sabatine, David A Morrow, Raphaelle Dumaine, Sabina A Murphy, Kieth E Boundy, Christopher P Cannon, C.Michael Gibson
Journal: Journal of the American College of Cardiology (2004)
Allergy to diazepam.
Authors: L Milner
Journal: BMJ (1977)

Vertical gaze palsy in barbiturate intoxicationParalysis of conjugate gaze is not a well-recognised sign of barbiturate intoxication in the conscious patient.1 2We describe here the occurrence of a vertical gaze palsy in a patient intoxicated with a medium-acting barbiturate. Case reportA 28-year-old Australian woman (75-5 kg) presented with a four-day history of right frontal headache, drowsiness, photophobia, ataxia, anorexia, and vomiting.She denied ingestion of drugs, other than prednisone (5 mg/ day) and theophyllin when required for her asthma, and there was no history of drug intoxication.There was no family history of adverse drug effects.She was afebrile and the general examination showed nothing abnormal.There was mild neck stiffness.She was drowsy and mildly dysarthric but could co-operate fully with the examination.There was mild engorgement of retinal veins in the right eye.Pupil size and reaction were normal.Horizontal gaze was full with bilateral fine gaze-evoked nystagmus in the supine position, which was unsustained when she sat up.Convergence was absent.Conjugate upward gaze was completely absent and no upward movement of the eyes occurred on forceful eye closure or with the oculocephalic manoeuvre.Downward gaze was full.The remainder of the examination showed nothing abnormal apart from generalised depression of deep tendon reflexes and mild ataxia of gait.
The Vulnerability of Court-Appointed Impartial Experts in Child-Custody Cases
Authors: William J. Curran
Journal: New England Journal of Medicine (1985)

Among the most hotly contested and emotional courtroom battles are those involving child-custody disputes. These are the cases that could not be settled amicably between the parties in divorce and separation actions. Reforms in divorce law have removed a great deal of the wrangling over grounds and guilt in the marital split itself, but no amount of procedural or substantive reform can eliminate conflict arising from the faith, love, hopes, and dreams wrapped up in the children produced by the relationship. It is estimated that by the end of this decade approximately one third of American children, before reaching the . . .
P1-178: Synchronous multisystemic(pulmonary and gastrointestinal) extranodal marginal zone lymphoma of malt type and two lung carcinomas with different histologic and immunophenotypic features
Authors: Duygu Gürel, Devrim Tayfur, Aydin Sanli, Onur Turan, Volkan Karacam, Atila Akkoclu, Aydanur Kargi
Journal: Journal of Thoracic Oncology (2007)
The relationship between albuminuria, MCP-1/CCL2, and interstitial macrophages in chronic kidney disease
Authors: K.S. Eardley, D. Zehnder, M. Quinkler, J. Lepenies, R.L. Bates, C.O. Savage, A.J. Howie, D. Adu, P. Cockwell
Journal: Kidney International (2006)
Management of Ovarian Stromal Cell Tumors
Authors: Nicoletta Colombo, Gabriella Parma, Vanna Zanagnolo, Alessandra Insinga
Journal: Journal of Clinical Oncology (2007)

To describe the clinical management of ovarian stromal cell tumors, which are a heterogeneous group of neoplasms that develop from the sex cords and the ovarian stroma.We reviewed the current evidence on the clinical management of these relatively rare ovarian malignancies, which are typically detected at an early stage and may recur as late as 30 years following the initial treatment. The overall prognosis is favorable with a long-term survival ranging from 75% to 90% for all stages. Adult granulosa cell tumor (GCT) is the most common malignancy among these tumors.Surgery is the cornerstone of initial treatment. In women of childbearing age and with disease limited to one ovary, a fertility-sparing surgery can be a reasonable approach. Tumor stage represents the most important clinical parameter of prognostic relevance. The value of postoperative adjuvant therapy for high-risk patients has not been proven by prospective randomized studies. Platinum-based chemotherapy is used currently for patients with advanced stages or recurrent disease, with an overall response rate of 63% to 80%. Taxane and platinum combination chemotherapy seems to be a reasonable candidate for future trials. Little evidence exists for the use of radiation or hormonal therapy, and these modalities should be restricted to selected cases. Given the propensity of GCT for late relapse, prolonged follow-up is required.Surgery remains the most effective treatment for ovarian stromal tumors and, whenever feasible, for relapsing disease. Platinum-based chemotherapy is currently used in metastatic or recurrent tumors.
Malignant Melanoma with Metastatic Rhabdomyosarcomatoid Transdifferentiation
Authors: Stefan Gattenlöhner, Eva-Bettina Brocker, Hans-Konrad Muller-Hermelink
Journal: New England Journal of Medicine (2008)

To the Editor: We report on the case of a 41-yearold man with a 2.1-cm primary malignant melanoma of the skin, located on the crown of the head.The tumor was stage pT4 (with invasion of contiguous structures), Clark level V, and 6 mm in thickness, with classic morphologic and immunohisto- Malignant Melanoma with Metastatic Rhabdomyosarcomatoid Transdifferentiation33p9 A Primary Malignant Melanoma B Lymph-Node Metastasis with Rhabdomyosarcomatoid Transdifferentiation C Rhabdoid-like Features of Primary Malignant Melanoma
Androgen Receptor Roles in Spermatogenesis and Fertility: Lessons from Testicular Cell-Specific Androgen Receptor Knockout Mice
Authors: Ruey-Sheng Wang, Shuyuan Yeh, Chii-Ruey Tzeng, Chawnshang Chang
Journal: Endocrine Reviews (2009)

Abstract Androgens are critical steroid hormones that determine the expression of the male phenotype, including the outward development of secondary sex characteristics as well as the initiation and maintenance of spermatogenesis. Their actions are mediated by the androgen receptor (AR), a member of the nuclear receptor superfamily. AR functions as a ligand-dependent transcription factor, regulating expression of an array of androgen-responsive genes. Androgen and the AR play important roles in male spermatogenesis and fertility. The recent generation and characterization of male total and conditional AR knockout mice from different laboratories demonstrated the necessity of AR signaling for both external and internal male phenotype development. As expected, the male total AR knockout mice exhibited female-typical external appearance (including a vagina with a blind end and a clitoris-like phallus), the testis was located abdominally, and germ cell development was severely disrupted, which was similar to a human complete androgen insensitivity syndrome or testicular feminization mouse. However, the process of spermatogenesis is highly dependent on autocrine and paracrine communication among testicular cell types, and the disruption of AR throughout an experimental animal cannot answer the question about how AR in each type of testicular cell can play roles in the process of spermatogenesis. In this review, we provide new insights by comparing the results of cell-specific AR knockout in germ cells, peritubular myoid cells, Leydig cells, and Sertoli cells mouse models that were generated by different laboratories to see the consequent defects in spermatogenesis due to AR loss in different testicular cell types in spermatogenesis. Briefly, this review summarizes these results as follows: 1) the impact of lacking AR in Sertoli cells mainly affects Sertoli cell functions to support and nurture germ cells, leading to spermatogenesis arrest at the diplotene primary spermatocyte stage prior to the accomplishment of first meiotic division; 2) the impact of lacking AR in Leydig cells mainly affects steroidogenic functions leading to arrest of spermatogenesis at the round spermatid stage; 3) the impact of lacking AR in the smooth muscle cells and peritubular myoid cells in mice results in similar fertility despite decreased sperm output as compared to wild-type controls; and 4) the deletion of AR gene in mouse germ cells does not affect spermatogenesis and male fertility. This review tries to clarify the useful information regarding how androgen/AR functions in individual cells of the testis. The future studies of detailed molecular mechanisms in these in vivo animals with cell-specific AR knockout could possibly lead to useful insights for improvements in the treatment of male infertility, hypogonadism, and testicular dysgenesis syndrome, and in attempts to create safe as well as effective male contraceptive methods.
P242 Patients Overestimate Their Degree of Asthma Control Despite the Presence of Symptoms: A UK Survey: Abstract P242 Table 1
Authors: M Fletcher, D Hiles, E Luck
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> Many patients with asthma overestimate the extent to which their symptoms are controlled, which may suggest that the real-world burden of the disease is greater than reported. This abstract reports data from a UK-based survey assessing the variation between patients’ perceptions of asthma control and their symptoms. <h3>Methods</h3> This was a cross-sectional online survey administered by YouGov plc (November 2011) to a panel of over 350,000 individuals. Panellists who had previously identified themselves as having asthma were invited by e-mail to participate in the survey. Responses were collated and analysed by YouGov and Insight Research Group. Overall, 1083 individuals completed the survey; 49% of respondents were aged over 55 years and 45% were male. Almost two-thirds (64%) of patients were using both reliever and preventer therapy and 17% were using reliever medication only. <h3>Results</h3> Most respondents reported that their asthma control was ‘very good’ (37%) or ‘good’ (42%). However, 19% of respondents described having uncontrolled asthma (i.e. ‘symptoms not very well managed’) at least once a month and 10% reported lack of asthma control at least once a week. In the 2 years prior to the survey, 12% of individuals had visited an accident-and-emergency department due to their asthma (ranging from 1 to 5 visits). Moreover, 41% of individuals used reliever medication at least once a day, and almost two-thirds experienced frequent (at least ‘sometimes’) day-time symptoms and over one-third had frequent night-time symptoms (Table). The most common day-time symptoms were coughing (experienced by 65% of individuals at least ‘sometimes’), wheezing (62%) and breathlessness (58%). Despite this, 91% of respondents were ‘very satisfied’ or ‘fairly satisfied’ (44% and 47%, respectively) with their level of asthma control, and 59% did not believe it was possible to improve control. <h3>Conclusions</h3> Patients are generally satisfied with their level of asthma control despite evidence of poor symptom control, suggesting a disconnection between patient perception of asthma control and actual asthma control. This suggests a need for further education to help patients better recognize the symptoms of poor asthma control and how this can help them aspire to greater asthma control.
Use of anabolic steroids has been reported by 9% of men attending gymnasiums
Authors: P. Korkia
Journal: BMJ (1996)

EDITOR,—F H Lloyd and colleagues report several cases of subfertility in male body builders who misused anabolic steroids.1 I would draw the authors' attention to a report commissioned by the Departments of Health for England, Scotland, and Wales, entitled Anabolic Steroid Use in Great Britain: An Exploratory Investigation.2

The research for the report investigated use of anabolic steroids in 21 gymnasiums in England, Scotland, and Wales and found that 119 …