tbuckley/cabot-search huggingface dataset:
Expression of classical and non-classical MHC class I antigens in murine hair follicles
Authors: R. PAUS, S. EICHMÜLLER, U. HOFMANN, B.M. CZARNETZKI, P. ROBINSON
Journal: British Journal of Dermatology (2006)

Not all keratinocytes in human and rat hair follicles express MHC class I antigens (MHC I). In the present study, we report the first immunohistological profile of classical and non‐classical MHC I expression in the skin of adolescent C57 BL‐6 mice during the induced hair cycle. MHC I immunoreactivity (H‐2b, H‐2Db) is absent in the matrix and inner root sheath of growing (=anagen) hair follicles, and the dermal papillae are H‐2b negative during catagen and telogen. This lack of normal MHC I expression may serve to sequester potentially damaging autoantigens from immune recognition. In addition, we present the first evidence of non‐classical MHC class I antigen expression in normal mammalian skin: during the entire hair cycle, the distal hair follicle shows strong Qa‐2 immunoreactivity, which appears to be restricted to an epithelial follicle compartment densely populated by gamma‐delta T cells with which Qa‐2 molecules may interact as part of a primitive antibacterial defense system of the follicle. The murine hair cycle is an attractive model for dissecting the functional roles of H‐2b and Qa‐2 molecules in hair biology and in related tissue‐interaction systems.
Downregulation of EGFR by a novel multivalent nanobody-liposome platform
Authors: Sabrina Oliveira, Raymond M. Schiffelers, Joris van der Veeken, Roy van der Meel, Ranitha Vongpromek, Paul M.P. van Bergen en Henegouwen, Gert Storm, Rob C. Roovers
Journal: Journal of Controlled Release (2010)
Specific Antivenene and Prednisone in Viper-bite Poisoning: Controlled Trial
Authors: H. A. Reid, P. C. Thean, W. J. Martin
Journal: BMJ (1963)

Since the pioneer work of Calmette (1894) and Fraser (1895) it has been generally assumed that specific antivenene is the most effective treatment available for snake bite.Many reports claim support for this assumption, but to the critical mind the impressions and conclusions are vitiated by the many variables in human snake-bite poisoning.In Malaya the most common cause of snake bite is the pit viper, Ancistrodon rhodostoma (Boie).In 1958 a limited supply of specific A. rhodostoma antivenene became avail- able for the first time in Malaya.Since the number of A. rhodostoma victims was much too high (Reid, Thean, and Martin, 1963) to allow each subject this specific antiserum, it was thought ethical to use the limited supply in controlled clinical trials.A first trial comparing the effect of the specific antivenene with that of non-specific polyvalent antivenene from the Haffkine Institute, India (which had been in routine use during the preceding five years in Malaya), suggested that specific antivenene benefited systemic poisoning but did not help local poisoning.With the proviso that patients with very severe systemic poisoning would be excluded or withdrawn from the next trial, we then compared the effects of specific antivenene with those in a control group receiving no antivenene.Since steroids have also been claimed to benefit victims of snake bite we included a third group given prednisone.* This excludes necrosis healing-time.
Cyclosporine- and FK506-induced sympathetic activation correlates with calcineurin-mediated inhibition of T-cell signaling.
Authors: T Lyson, L D Ermel, P J Belshaw, D G Alberg, S L Schreiber, R G Victor
Journal: Circulation Research (1993)

Cyclosporine A (CsA)-induced hypertension appears to be caused in part by neurogenic vasoconstriction, but the mechanism by which CsA activates the sympathetic nervous system is unknown. In T lymphocytes, the cellular target of CsA and the macrolide immunosuppressant FK506 (as complexes with their endogenous cytoplasmic receptors, or immunophilins) is the Ca(2+)-calmodulin-dependent phosphatase calcineurin. The presence of calcineurin and its colocalization with immunophilin in the brain led us to hypothesize that the phosphatase also mediates CsA-induced sympathetic activation. We now report that sympathetic activity and arterial pressure in rats are increased not only by CsA but also by FK506, which is structurally unrelated to CsA but inhibits the same calcineurin-sensitive T-cell signaling pathway. In contrast, sympathetic activity and blood pressure are not increased by rapamycin, which forms an immunophilin complex that does not bind calcineurin. Furthermore, CsA- and FK506-induced sympathetic activation is attenuated for drug analogues possessing modest changes in molecular structure in a way that closely parallels the ability of each analogue to inhibit calcineurin-mediated T-cell signaling. These results implicate an important role for extralymphoid (ie, neuronal) calcineurin in mediating immunosuppressive drug toxicity.
Catheterisation in elderly women is no "easy" option
Authors: V. Aylett
Journal: BMJ (2001)

EDITOR—In their review of the management of urinary incontinence in women, Thakar and Stanton say that patients with chronic urinary incontinence, particularly elderly patients, may be easier to manage with a permanent indwelling catheter.1 As one of the “geriatric giants” described by Isaacs in 1992, urinary incontinence is a serious problem in older patients, with a prevalence of one in five to 10 in women older than …
Polymorphonuclear Leukocytes in Non-Insulin-dependent Diabetes Mellitus: Abnormalities in Metabolism and Function
Authors: Jadwiga M. Alexiewicz
Journal: Annals of Internal Medicine (1995)

Objective: To determine basal levels of cytosolic calcium ([Ca2+]i) and phagocytic activity in polymorphonuclear leukocytes (PMNLs) from patients with non–insulin-dependent diabetes (NIDDM). Design: Prospective cohort study. Setting: A university-county hospital. Measurements: Cytosolic calcium levels, adenosine triphosphate (ATP) content, and phagocytosis of PMNLs from patients with NIDDM and from controls. Intervention: In patients with NIDDM, we evaluated the effect of treatment with an oral hypoglycemic agent (glyburide) on [Ca2+]i levels, ATP content, and the phagocytosis of PMNLs. Patients: 22 controls and 34 patients with NIDDM were examined. Fifteen patients were studied before and after 3 months of treatment with glyburide. Results: Polymorphonuclear leukocytes from patients with NIDDM showed significantly elevated basal levels of [Ca2+]i (68 ± 9.6 compared with 43 ± 4.9 nmol/L; P < 0.01); reduced ATP content (1.30 ± 0.58 compared with 2.35 ± 0.45 nmol/106PMNLs; P < 0.01); and impaired phagocytosis (117 ± 21.0 compared with 145 ± 17.4 µg oil/107PMNLs per minute; P < 0.01) compared with controls. There was a direct and significant correlation (P < 0.01, r = 0.80) between [Ca2+]i levels in PMNLs and serum glucose levels and an inverse correlation between phagocytic ability and [Ca2+]i levels (P < 0.01; r = 0.62) as well as between phagocytic activity and fasting serum glucose levels (P < 0.01, r = 0.54) in patients with NIDDM. Glyburide therapy resulted in significant reduction in fasting serum glucose levels; in PMNLs, this treatment resulted in a significant reduction in [Ca2+]i levels, a significant increase in ATP content, and a significant improvement of phagocytosis. Conclusions: Patients with NIDDM have elevated [Ca2+]i levels in PMNLs. This abnormality is probably induced by hyperglycemia and is primarily responsible for the impaired phagocytosis seen in these patients.
Antibody to intermediate filaments of the cytoskeleton.
Authors: O A Osung, M Chandra, E J Holborow
Journal: Annals of the Rheumatic Diseases (1982)

IgM antibodies against cultures of intermediate filaments (IMF) of the cytoskeleton were demonstrated by immunofluorescence in the sera of 94 (80%) of 118 patients with seropositive rheumatoid arthritis. These antibodies reacted with IMF in cultures of both human fetal fibroblasts and laryngeal carcinoma (HEp2) cells. Of 10 patients from whom paired synovial fluids were also available 8 had anti-IMF antibodies in both serum and fluid. In seronegative RA the incidence of anti-IMF was 40%, in ankylosing spondylitis 25%, in osteoarthrosis 16%, and in normal subjects 14%. Only a minority of RA sera positive for anti-IMF antibodies were also positive for smooth muscle antibody. Absorption experiments suggest that in RA anti-IMF is directed at the intermediate filament protein, vimentin.
GW25-e5231 Activin receptor-like kinase 7 silencing alleviates cardiomyocyte apoptosis, cardiac fibrosis and left ventricular dysfunction in type 2 diabetic rat
Authors: Liu Lin, Ming Zhong, Li Li, Yuanyuan Shang, Zhihao Wang, Yun Zhang, Yuguo Chen, Wei Zhang, Mengxiong Tang
Journal: Journal of the American College of Cardiology (2014)
Type II NKT cells differentially regulate CD4 T cell subsets
Authors: Faith C Robertson, Xiuju Lu, Masaki Terabe, Jay A Berzofsky
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Natural killer T (NKT) cells lie at the interface between the innate and adaptive immune systems and are important mediators of tumor immunosurveillance. This CD1d-restricted lymphoid population recognizes lipid antigen and can rapidly produce an array of cytokines and chemokines
The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS)
Authors: Jeffrey L. Kaufman
Journal: JAMA (1997)

To the Editor.  —The MIDAS study by Dr Borhani et al1uses high-resolution ultrasound to determine the thickness of carotid artery intima as a marker for progression of atherosclerosis. However, the type of ultrasound probe used and its frequency were not defined in the protocol. The measurements were reported to the nearest 0.01 mm, but the statistical analysis and results reported data to the third decimal place. Moreover, I have trouble believing their report on the basis of the physics of ultrasound probes now commercially available. Axial resolution of ultrasound probes is related to the frequency of the probe; the maximum resolution for 7.5-to 10-MHz probes is reported to range ±0.2 mm and for 5-MHz probes ±mm.2For a 2-cycle system, the resolution is 1.54 divided by the frequency in megahertz. Therefore, the data analysis and results of this study may well overstate the ability of current
THE SURGERY OF THE BILIARY TRACT.ESPECIALLY THE INDICATIONS FOR OPERATION AND THE IMPORTANCE OF DRAINAGE.
Authors: MAURICE H. RICHARDSON
Journal: JAMA (1904)

The present communication seems to me justified only in the light of experiences which I have had during the past winter. We are still far from a satisfactory solution of many questions concerning the surgery of the biliary tract. The following are some of these questions: (a) Should gallstones be removed even if they cause no symptoms? (b) What is the importance of biliary drainage after opening the gall bladder or gall ducts? (c) What is the best way of preventing hernia after operations on the biliary passages? (d) What is the significance of the biliary fistula? From the beginning, hernia in the scar and biliary fistula have been enough to dampen the surgeon's enthusiasm for a procedure which, in many other respects, is one of the most brilliant and effective in modern surgery. The cause of hernia after operations on the biliary tract is the long incision and
Colorectal neoplasm detection using virtual colonoscopy: a feasibility study
Authors: H M Fenlon, D P Nunes, P D Clarke, J T Ferrucci
Journal: Gut (1998)

Virtual colonoscopy is a potentially powerful tool for non-invasive colorectal evaluation. In vitro studies have established its accuracy in simulated polyp detection but little data exist regarding its use in clinical practice.To evaluate the ability of virtual colonoscopy to detect colorectal cancers and polyps in patients with endoscopically proven colorectal neoplasms and to correlate the findings of virtual colonoscopy with those of conventional colonoscopy, surgery, and histopathology.Thirty eight patients with endoscopic findings suggestive of colorectal carcinoma.Virtual colonoscopy was performed using thin section helical computed tomography (CT) of the abdomen and pelvis after rectal insufflation of room air. Commercially available software was used to generate endoscopic "fly through" examinations of the colon from the CT data. Results were correlated with the findings of conventional colonoscopy and with the surgical and histopathological outcome in each case.Thirty eight pathologically proven colorectal cancers and 23 adenomatous polyps were present. On virtual colonoscopy, all cancers and all polyps measuring greater than 6 mm in size were identified; there were two false positive reports of polyps. On conventional colonoscopy, there was one false positive report of a malignant sigmoid stricture; four subcentimetre polyps were overlooked. Virtual colonoscopy enabled visualisation of the entire colon in 35 patients; conventional colonoscopy was incomplete in 14 patients. Virtual colonoscopy correctly localised all 38 cancers, compared with 32 using conventional colonoscopy.Virtual colonoscopy is a feasible method for evaluating the colon; it may have role in diagnosis of colorectal cancer and polyps.
Breast cancer and oral contraceptives: findings in Oxford-Family Planning Association contraceptive study.
Authors: M P Vessey, K McPherson, R Doll
Journal: BMJ (1981)

Among the 17 032 women taking part in the Oxford-Family Planning Association contraceptive study, 72 were first diagnosed as having breast cancer between the date they were admitted to the study and 1 September 1980. The relative risk of developing the disease in women who had used oral contraceptives in comparison with those who had never used them was estimated to be 0.96 (95% confidence limits 0.59 to 1.63). Among women aged under 35 years, the corresponding relative risk (based on only 14 women with breast cancer) was estimated to be 0.61. No relation was apparent between the risk of developing breast cancer and duration of oral-contraceptive use or interval since first oral-contraceptive use in any age group. The data in this study are thus reassuring; but observations based on women with long-term use of oral contraceptives, especially those starting to use the preparations at an early age, are few.
TCT-764 Safety and Biocompatibility of the Coherex WaveCrest™ Left Atrial Appendage Occluder in a 30-Day Canine Study
Authors: Yanping Cheng, Jenn McGregor, Robert Sommer, William Gray, Daryl Edmiston, Gerard Conditt, Genghua Yi, Armando Tellez, Serge Rousselle, Juan Granada, Greg Kaluza
Journal: Journal of the American College of Cardiology (2012)
Peritoneal Dialysis
Authors: R. O. Burns, L. W. Henderson, E. B. Hager, John P. Merrill
Journal: New England Journal of Medicine (1962)

THE technic of peritoneal dialysis was first used to treat uremia in man about forty years ago.1 Early complications of overhydration, infection and peripheral vascular collapse, together with the inadequacy of the catheters used and the difficulty in draining the irrigating fluid, did much to prevent its development as a routine procedure. The procedure was extensively explored by Frank, Seligman and Fine,2 using surgically inserted sump drains. With this technic, however, infection was common and prevented its widespread use. The introduction of a method employing a plastic catheter inserted through the hollow trocar used for an ordinary abdominal paracentesis has . . .
MR-01 * MicroRNA-145 REGULATES JAM-A EXPRESSION AND COMPROMISES GLIOBLASTOMA MAINTENANCE
Authors: A. Alvarado, M. Li, P. Sathyan, S. Majumder, J. Rich, J. Lathia
Journal: Neuro-Oncology (2014)

Glioblastoma is composed of heterogeneous cellular populations, including self-renewing, tumorigenic cancer stem cells (CSCs). Discrete anatomical niches have been described where CSCs communicate with their surroundings to promote their self-renewal, tumor maintenance and increased resistance to conventional therapies. Therefore, signaling molecules involved in cell-cell interactions and the associated regulatory mechanisms are vital to CSC function. CSC interaction with their niche via adhesion proteins is critical for CSC maintenance, and enhanced adhesion is a hallmark of stemness. In the context of cancer, gene expression is regulated through the upregulation or downregulation of specific microRNAs (miRNAs). The interaction between miRNAs and proteins involved in niche adhesion and communication remains largely unexplored. Junctional adhesion molecule A (JAM-A) is a CSC-specific adhesion protein and its targeting decreases self-renewal and tumorigenicity. To determine whether JAM-A promotes self-renewal, we overexpressed JAM-A and observed an increase in proliferation, self-renewal, and tumor formation. In order to link this adhesion mechanism to a larger signaling network, we evaluated the upstream mechanisms by which JAM-A is regulated and specifically expressed by CSCs. By analyzing miRNAs, we found that JAM-A expression is suppressed by miR-145 and confirmed JAM-A as a direct target of mir-145 using luciferase constructs. miR-145 has previously been described to be a negative regulator of glioblastoma growth, and we found that non-CSCs expressed high levels of miR-145 while CSCs expressed low miR-145, correlating to differences in JAM-A expression between CSCs and non-CSCs. Introduction of miR-145 into CSCs decreased self-renewal, stem cell marker expression (SOX2, OCT4 and NANOG) and activation of self-renewal pathways (STAT3 and AKT). Mechanistic studies are in progress to determine how miR-145 and JAM-A interact to control stem cell and self-renewal pathways. Our results link CSC-specific adhesion to a microRNA regulatory network that is altered in glioblastoma.
Abstract 4528: Genotoxic and estrogenic properties of new antiestrogens
Authors: Shinya Shibutani, Y. R. Santosh Laxmi, Naomi Suzuki, Yoshinori Okamoto
Journal: Cancer Research (2011)

Abstract Long-term administration of tamoxifen (TAM) to breast cancer patients and women at high risk of developing this disease gives serious side effects, including endometrial cancer. These side-effects are due to the DNA damaging and/or estrogenic action of the drug. Several antiestrogens have been developed in last three decades, but were dropped out from the clinical trials due to their undesirable effects on the uterus. To avoid this serious side-effect, we have synthesized a new triphenylethylene antiestrogen, E-3-{4-[(E)-4-chloro-1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]-phenyl} acrylic acid (SS1020) and a new benzopyran antiestrogen, 2E-3-{4-[(7-hydroxy-2-oxo-3-phenyl-2H-chromen-4-yl)-methyl]-phenyl}-acrylic acid (SS5020). SS1020 and SS5020 had antitumor potential much higher than that of TAM or other antiestrogens at the human equivalent doses (TAM 0.3-1.0 mg/kg/day), against 7,12-dimethylbenz(a)anthracene-induced mammary tumors in rats or human MCF-7 breast cancer xenograft implanted into athymic nude mice. To evaluate their genotoxic activity, the capability of forming hepatic DNA adducts in rats was determined. When rats were treated orally at a dose molar equivalent to TAM (20 mg/kg/day), a high level (∼1 adduct/105 nucleotides) of DNA adducts was detected in TAM-treated rats whereas no DNA adducts were observed in rats treated with SS1020 or SS5020. To evaluate the estrogenic potential, the uterotrophic activity of our compounds was determined in ovariectomized (OVX) rats at a dose molar equivalent to TAM (10 mg/kg/day), which is 30 times higher than the human equivalent dose of TAM. TAM had high uterotrophic activity while SS1020 and SS5020 did not present significant uterotrophic activity. Therefore, SS1020 and SS5020, lacking estrogenic and genotoxic actions, are expected not to induce reproductive cancers. Interestingly, the antitumor activities of several antiestrogens examined were, rather, increased significantly to the lowering uterotrophic activity evaluated with OVX-rats, but not to their antiproliferative activities against cultured estrogen receptor positive human MCF-7 breast cancer cells. The use of uterotrophic assay, not antiproliferative assay, may be a suitable screening system to exploit antiestrogen alternatives. Non-genotoxic and non-estrogenic SS1020 and SS5020, having strong antitumor potency superior to that of TAM, could be safer alternatives for breast cancer therapy and prevention. 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 4528. doi:10.1158/1538-7445.AM2011-4528
Prevention of Depression in At-Risk Adolescents
Authors: Judy Garber, Gregory N. Clarke, V. Robin Weersing, William R. Beardslee, David A. Brent, Tracy R. G. Gladstone, Lynn L. DeBar, Frances L. Lynch, Eugene D’Angelo, Steven D. Hollon, Wael Shamseddeen, Satish Iyengar
Journal: JAMA (2009)

A COMMON AND episodic condition that is associated with difficulties in relationships, impaired school and work performance, and increased risk for substance abuse and suicide. 1 Adolescent-onset depression is strongly associated with chronic and recurrent depression in adulthood, 2,3 which is a leading cause of morbidity and mortality. 4Despite substantial progress in the treatment of adolescent depression (ie, acute response and remission rates are about 60% and 30%, respectively), 5 only about 25% of depressed youth receive treatment 6 and at least 20% develop recurrent, persistent, and chronic depression that is very difficult to treat. 5,7The serious developmental consequences of adolescent depression and the associated treatment challenges once it has developed underscore the need for programs aimed at prevention. 8 One of the most potent and clinically salient risk factors for the development of depression in youth is parental depression. 9Offspring of de-
Ewing’s sarcoma precursors are highly enriched in embryonic osteochondrogenic progenitors
Authors: Miwa Tanaka, Yukari Yamazaki, Yohei Kanno, Katsuhide Igarashi, Ken-ichi Aisaki, Jun Kanno, Takuro Nakamura
Journal: Journal of Clinical Investigation (2014)

Ewing's sarcoma is a highly malignant bone tumor found in children and adolescents, and the origin of this malignancy is not well understood. Here, we introduced a Ewing's sarcoma-associated genetic fusion of the genes encoding the RNA-binding protein EWS and the transcription factor ETS (EWS-ETS) into a fraction of cells enriched for osteochondrogenic progenitors derived from the embryonic superficial zone (eSZ) of long bones collected from late gestational murine embryos. EWS-ETS fusions efficiently induced Ewing's sarcoma-like small round cell sarcoma formation by these cells. Analysis of the eSZ revealed a fraction of a precursor cells that express growth/differentiation factor 5 (Gdf5), the transcription factor Erg, and parathyroid hormone-like hormone (Pthlh), and selection of the Pthlh-positive fraction alone further enhanced EWS-ETS-dependent tumor induction. Genes downstream of the EWS-ETS fusion protein were quite transcriptionally active in eSZ cells, especially in regions in which the chromatin structure of the ETS-responsive locus was open. Inhibition of β-catenin, poly (ADP-ribose) polymerase 1 (PARP1), or enhancer of zeste homolog 2 (EZH2) suppressed cell growth in a murine model of Ewing's sarcoma, suggesting the utility of the current system as a preclinical model. These results indicate that eSZ cells are highly enriched in precursors to Ewing's sarcoma and provide clues to the histogenesis of Ewing's sarcoma in bone.