tbuckley/cabot-search huggingface dataset:
Mechanisms of eosinophil adherence to cultured vascular endothelial cells. Eosinophils bind to the cytokine-induced ligand vascular cell adhesion molecule-1 via the very late activation antigen-4 integrin receptor.
Authors: A Dobrina, R Menegazzi, T M Carlos, E Nardon, R Cramer, T Zacchi, J M Harlan, P Patriarca
Journal: Journal of Clinical Investigation (1991)

We have examined the mechanisms involved in the adherence of normal peripheral blood eosinophils to cultured human umbilical vein endothelial cells (HEC) under three conditions: (a) adherence in the absence of treatment of HEC or eosinophils with activating agents (basal adherence); (b) adherence induced by stimulation of eosinophils with phorbol ester (eosinophil-dependent adherence); and (c) adherence induced by pretreatment of HEC with LPS, tumor necrosis factor (TNF), or IL-1 (endothelial-dependent adherence). A mechanism was identified that was equally active in basal, eosinophil-dependent, and endothelial-dependent adherence. This mechanism was optimally active in the presence of both Ca++ and Mg++, and reduced in the presence of Ca++ only or Mg++ only. Furthermore, like the other mechanisms of eosinophil adherence, it was active at 37 degrees C but not at 4 degrees C. A second mechanism of adherence was involved in eosinophil- and in endothelial-dependent adherence. This mechanism was dependent on the CD11/CD18 adhesion complex of eosinophils (i.e., inhibited by anti-CD18 MAb) and it was active in the presence of Ca++ and Mg++ or Mg++ only, but not Ca++ only. The third mechanism of adherence was specific for endothelial-dependent adherence. It involved the endothelial ligand vascular cell adhesion molecule-1 (VCAM-1) and the eosinophil receptor very late activation antigen-4 (VLA-4, CD49d/CD29, i.e., inhibited by anti-VCAM-1 MAb or anti-VLA-4 MAb). This mechanism was active in the presence of Ca++ and Mg++ but not of Ca++ only or Mg++ only, and was not up- or downregulated when eosinophils were stimulated with phorbol ester. In contrast, the endothelial leukocyte adhesion molecule-1 (ELAM-1), that binds neutrophils and monocytes, was not involved in eosinophil adherence to LPS-, TNF-, or IL-1-stimulated HEC (i.e., not inhibited by anti-ELAM-1 MAb). We conclude that eosinophils, like monocytes and lymphocytes, bind to the cytokine-induced endothelial ligand VCAM-1 via the integrin receptor VLA-4.
Usefulness of Bone Imaging in Diagnosis of Sternocostoclavicular Hyperostosis
Authors: NOBUAKI OTSUKA, MASAO FUKUNAGA, TERUKI SONE, KIYOHISA NAGAI, TATSUSHI TOMOMITSU, SHINICHI YANAGIMOTO, AKIRA MURANAKA, SHIMATO ONO, RIKUSHI MORITA
Journal: Clinical Nuclear Medicine (1986)

Four Patients with sternocostoclavicular hyperostosis showing characteristic abnormal uptake on bone imageing are described Bone imaging was useful in the diagnosis of sternocostoclavicular hyperostosis.
PITYRIASIS LICHENOIDES AND PARAPSORIASIS.
Authors: F.R.C.P. John T. Ingram
Journal: British Journal of Dermatology (1953)

Journal Article PITYRIASIS LICHENOIDES AND PARAPSORIASIS. Get access JOHN T. INGRAM, M.D., F.R.C.P. JOHN T. INGRAM, M.D., F.R.C.P. Physician in Charge of the Skin Department, The General Infirmary, Leeds; Lecturer on Diseases of the Skin, The University of Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 65, Issue 9, 1 September 1953, Pages 293–299, https://doi.org/10.1111/j.1365-2133.1953.tb13754.x Published: 01 September 1953
Effects of chloride and extracellular fluid volume on bicarbonate reabsorption along the nephron in metabolic alkalosis in the rat. Reassessment of the classical hypothesis of the pathogenesis of metabolic alkalosis.
Authors: J H Galla, D N Bonduris, R G Luke
Journal: Journal of Clinical Investigation (1987)

Volume expansion has been considered essential for the correction of chloride-depletion metabolic alkalosis (CDA). To examine the predictions of this hypothesis, rats dialyzed against 0.15 M NaHCO3 to produce CDA and controls, CON, dialyzed against Ringer-HCO3 were infused with either 6% albumin (VE) or 80 mM non-sodium chloride salts (CC) added to 5% dextrose (DX) and studied by micropuncture. CDA was maintained in rats infused with DX. VE expanded plasma volume (25%), maintained glomerular filtration rate (GFR), but did not correct CDA despite increased fractional delivery of total CO2 (tCO2) out of the proximal tubule (36 +/- 2%) as compared with VE/CON (24 +/- 4%; P less than 0.05). In contrast, CC corrected CDA despite volume contraction (-16%) and lower GFR than CC/CON; proximal tCO2 delivery in CC/CDA (29 +/- 4%) did not differ from VE/CDA. CC was associated with an increment in tCO2 excretion. The data strongly suggest that maintenance and correction of CDA are primarily dependent upon total body chloride and its influences on intrarenal mechanisms and not on the demands of sodium or fluid homeostasis.
<i>O6-Methylguanine-DNA Methyltransferase</i> Regulation by p53 in Astrocytic Cells
Authors: Michael D. Blough, Magdalena C. Zlatescu, J. Gregory Cairncross
Journal: Cancer Research (2007)

Abstract Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter (i.e., gene silencing) occurs in 40% to 50% of patients with glioblastoma and predicts benefit from temozolomide chemotherapy; when unmethylated, MGMT repairs DNA damage induced by temozolomide, contributing to chemoresistance. In this study, we tested the hypothesis that MGMT is regulated by p53 in astrocytic cells, the precursors of which may give rise to glioblastoma. p53 is of interest because, in addition to often being mutated in glioblastoma, inactivation sensitizes some astrocytoma cell lines to temozolomide. MGMT expression was examined in neonatal murine astrocytes and SF767 human astrocytic glioma cells following p53 inactivation by knockout (murine only) or RNAi methods. MGMT mRNA and protein were detected in murine wild-type p53 astrocytes. However, in knockout murine astrocytes and wild-type cells in which p53 was inhibited by RNAi, MGMT expression was reduced by &amp;gt;90%. This effect of p53 on MGMT expression was unrelated to MGMT promoter methylation—in both wild-type and p53-null astrocytes, the MGMT promoter was unmethylated. In wild-type astrocytes, the p53 protein localized to a regulatory region of the MGMT promoter. In SF767 human astrocytic glioma cells, transient knockdown of p53 led to the down-regulation of MGMT gene expression. In murine astrocytes and SF767 cells, p53 regulates MGMT expression without affecting promoter methylation; in astrocytes, this effect may be due to direct binding of p53 to the MGMT promoter. These results imply that the best use of temozolomide requires a thorough understanding of MGMT regulation. [Cancer Res 2007;67(2):580–4]
Textbook of Pathology
Authors: Milton G. Bohrod
Journal: JAMA (1966)

Written for students of medicine and adequate for the purpose, this work is not likely to attract either clinicians or pathology residents. The language is good but certainly not spritely. Nor is the reading made easier by the solid blocks of type which result from relegating all the illustrations to a separate volume. An inquiry into the psychology of reading might help authors and publishers of textbooks.  The most attractive feature of this work will be its illustrations, although even here the book disappoints. The gross pictures are in general adequate, although some come from a time when color photography was not yet what it is today. The photomicrographs, on the other hand, are often in better color but are mostly at unsuitable magnifications. And when it is necessary to point out what those dots in the right-hand corner represent, perhaps the picture has failed in its purpose.  There are
ChIP-Seq identification of weakly conserved heart enhancers
Authors: Matthew J Blow, David J McCulley, Zirong Li, Tao Zhang, Jennifer A Akiyama, Amy Holt, Ingrid Plajzer-Frick, Malak Shoukry, Crystal Wright, Feng Chen, Veena Afzal, James Bristow, Bing Ren, Brian L Black, Edward M Rubin, Axel Visel, Len A Pennacchio
Journal: Nature Genetics (2010)
GENERALIZED EDEMA OCCURRING ONLY AT THE MENSTRUAL PERIOD
Authors: WILLIAM A. THOMAS
Journal: JAMA (1933)

In enumerating the factors concerned in edema, one has come to recognize (though not always to explain) a number of conditions most commonly associated with the phenomenon, such as alterations in chemical and mineral balance, metabolic disturbances within the tissues, changes in colloidal state of dispersion, quantitative and qualitative changes in serum proteins, or endocrine dysfunction, and is able at times to deal empirically with the conditions and to obtain satisfactory results. Occasionally, however, one encounters situations entirely unique in so far as these recognized factors are concerned. It is the purpose of this paper to present two cases of generalized massive edema occurring only at the menstrual periods. As originally presented, the theme of the paper was edema, but the neurologic and gynecologic phases so overwhelmed the picture, and the internists had so little to contribute, that its appearance in this section is not unnatural. The first case has
Frequency analysis of cytotoxic T lymphocyte precursors in chimeric mice. Evidence for intrathymic maturation of clonally distinct self-major histocompatibility complex- and allo-major histocompatiblilty complex-restricted virus-specific T cells.
Authors: H Wagner, C Hardt, R Bartlett, H Stockinger, M Röllinghoff, H Rodt, K Pfizenmaier
Journal: The Journal of Experimental Medicine (1981)

To study whether the thymic major histocompatibility complex (MHC) imposes a constraint on the receptor repertoire of maturating cytotoxic T lymphocyte (CTL) precursors, the restriction phenotypes of virus-specific CTL of MHC-compatible and of MHC-incompatible thymus- and bone marrow-grafted (A X B)F1 chimeric mice were compared. Dependent on the mode of in vitro sensitization, thymocytes or splenocytes of both types of chimeric mice generated Sendai virus-specific, self-MHC-or allo-MHC-restricted CTL. By applying the limiting-dilution technique, the CTL-precursor (CTL-P) frequencies of self-MHC-restricted and allo-MHC-restricted virus-specific T cells as well as of alloreactive T cells were determined. The data obtained revealed that independent of MHC differences between thymus and bone marrow, the frequencies of self-MHC-restricted and allo-MHC-restricted CTL-P were comparable, and in the same older of magnitude as those previously determined in conventionally reared mice. Self-MHC-restricted, virus-specific CTL-P were in a three- to fivefold excess over allo-MHC-restricted CTL-P. A segregation analysis revealed that clonally distinct CTL-P give rise to either self-restricted or allo-MHC-restricted, virus-specific CTL. Both sets were found not only in the spleen, but also in the thymus of chimeric mice, formally demonstrating the intrathymic differentiation pathway of self-MHC as well of allo-MHC-restricted CTL-P. These data reveal no major constraint of the thymic MHC on the capacity of T cells to recognize viral antigens either in the context of self-MHC or of allogeneic MHC products.
Circadian Rhythms of Pineal Function in Rats
Authors: SUE A. BINKLEY
Journal: Endocrine Reviews (1983)

MELATONIN is believed to be synthesized in the pineal gland from serotonin by a two-step pathway. N-Acetyltransferase (NAT) catalyzes the acetylation of serotonin (5HT) by acetyl coenzyme A (AcCoA) to form N-acetylserotonin (NAS); hydroxyindole-O-methyltransferase (HIOMT) catalyzes the methylation of NAS by S-adenyosyl methionine (SAM) to make melatonin (MEL, MT). The activities of the enzymes are easily measured with radiochemical assays (1–3). Serotonin is found in pinealocytes (70%) and in the sympathetic nerve terminals (30%) in the pineal gland. It is thought that pinealocytes take up tryptophan from the blood but that the presence of serotonin in the nerve terminals represents uptake by the terminals (4). Tryptophan-5-hydroxylase and aromatic L-amino acid decarboxylase convert the tryptophan to serotonin (4). There are several aspects of pineal metabolism which make it unique. First, the pineal gland appears to be the principal source of rhythmically produced melatonin and the pineal gland was the tissue in which the indole hormone, melatonin, was discovered (5).
OC-103 Tumour regression grading correlates to survival in oesophago-gastric cancer. A report of current survival outcomes following neo-adjuvant chemotherapy: Abstract OC-103 Table 1
Authors: A M Reece-Smith, I Soomro, S madhusudan, S L Parsons
Journal: Gut (2012)

<h3>Introduction</h3> Patients who demonstrate a histological response to chemotherapy as determined by tumour regression grading (TRG) are known to have improved survival.<sup>1 2</sup> We report current survival expectations for patients following neo-adjuvant chemotherapy and resection of gastro-oesophageal cancer. <h3>Methods</h3> TRG was determined by a specialist pathologist in 250 patients after chemotherapy, and survival outcomes were assessed by Kaplan–Meier analysis of patients divided into responder (Mandard TRG 1–3) and non-responder (TRG 4&amp;5) groups, with log-rank comparisons. <h3>Results</h3> After a median follow-up of 54.4 months survival was found to be improved in those with histological response to chemotherapy (p&lt;0.001). Median survival was estimated to be 34.0 months and 21.2 months in oesophageal adenocarcinoma responders and non-responders and this was statistically significant (p=0.050). Junctional cancers demonstrated the largest survival difference at 51.1 months compared to 24.6 months (p=0.003). In gastric cancers the median survival was yet to be reached for responders and was 35.2 months for non-responders. However, smaller numbers in this group led to loss of statistical power (p=0.166). A higher proportion of patients with good response to chemotherapy was not seen using MAGIC regimen (Pearson χ<sup>2</sup> p=0.616). Good response to chemotherapy (TRG1-3) was associated with lower incidence of positive CRM (p=0.021) <h3>Conclusion</h3> Tumour regression grading is a useful predictor of overall survival allowing clinicians greater ability to counsel their patients. However, MAGIC therapy appears to improve survival possibly through mechanisms other than simply increasing the proportion of patients that have histological response. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Becker</b>, <i>et al. Ann Surg</i> 2011;<b>253</b>:934–9. 2. <b>Fareed</b>, <i>et al. Histopathology</i> 2009;<b>55</b>:399–406.
A Predictive Morphometric Model for the Obstructive Sleep Apnea Syndrome
Authors: Clete A. Kushida
Journal: Annals of Internal Medicine (1997)

Background: Mathematical formulas have been used to clinically predict whether patients will develop the obstructive sleep apnea syndrome (OSAS). However, these models do not take into account the disproportionate craniofacial anatomy that accompanies OSAS independently of obesity. Objective: To determine the accuracy of a morphometric model, which combines measurements of the oral cavity with body mass index and neck circumference, in predicting whether a patient has OSAS. Design: 6-month prospective study. Setting: University-based tertiary referral sleep clinic and research center. Participants: 300 consecutive patients evaluated for sleep disorders for the first time. Measurements: Body mass index, neck circumference, and oral cavity measurements were obtained, and a model value was calculated for each patient. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. Sleep apnea was defined as more than five episodes of apnea or hypopnea per hour of sleep. Results: The morphometric model had a sensitivity of 97.6% (95% CI, 95% to 98.9%), a specificity of 100% (CI, 92% to 100%), a positive predictive value of 100% (CI, 98.5% to 100%), and a negative predictive value of 88.5% (CI, 77% to 96%). No significant discrepancies were revealed in tests of intermeasurer and test-retest reliability. Conclusions: The morphometric model provides a rapid, accurate, and reproducible method for predicting whether patients in an ambulatory setting have OSAS. The model may be clinically useful as a screening tool for OSAS rather than as a replacement for polysomnography.
Advertising and Our Journal
Authors: ROBERT H. MOSER
Journal: Annals of Internal Medicine (1977)

Editorials1 July 1977Advertising and Our JournalROBERT H. MOSER, M.D., F.A.C.P.ROBERT H. MOSER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-87-1-114 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe uncertain romance between scholarly journals and the drug industry has long been like a marriage of convenience between partners who become friends ultimately, not because they were very fond of each other originally, but because they needed each other.The fact is that without the financial support of drug houses theAnnals of Internal Medicinewould cost a full-rate subscriber about $37.00 per year instead of $25.00 (and members of the College an increase in dues to $92.00 per year). This fact also applies to all other peer-review journals in clinical medicine. This is what justifies the incorporation of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ROBERT H. MOSER, M.D., F.A.C.P.Affiliations: American College of Physicians PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byConflicts between Commercial and Scientific Interests in Pharmaceutical Advertising for Medical JournalsThe “Fourth Part” of Pediatrics : 50 Years of Display AdvertisingAn analysis of advertisements in the Journal of the American Academy of Dermatology, 1980 and 1990Pharmaceutical Advertisements in Leading Medical Journals: Experts' AssessmentsMichael S. Wilkes, MD, MPH, Bruce H. Doblin, MD, MPH, Martin F. Shapiro, MD, PhDPharmaceutical Advertising and the Medical JournalAnniversary and AdvertisementsERIC E. LETOVSKY 1 July 1977Volume 87, Issue 1Page: 114-115KeywordsDrugs ePublished: 1 December 2008 Issue Published: 1 July 1977 PDF downloadLoading ...
Acute and chronic graft-vs-host reaction in skin: report of two cases
Authors: J. M. MASCARO, C. ROZMAN, J. PALOU†, A. GRAÑENA, T. CASTEL†, E. FELIU, J. MALLOLAS†
Journal: British Journal of Dermatology (1980)

SUMMARY The cutaneous changes of the acute form of graft-vs-host reaction are described in two patients who underwent bone marrow transplantation for treatment of severe aplastic anaemia. One patient went on to develop a chronic reaction of the lichenoid type. Histopathology confirmed the presence of ‘satellite cell necrosis’ from the acute stage of the disease onwards. Direct immunofluorescence showed deposits of immunoglobulin (IgG, IgM), fibrinogen and complement on the necrotic keratinocytes, whilst the basement membrane was positive for C3. These findings suggest that humoral immunity as well as cellular immunity may play a part in the production of the rash.
Abstract 2652: Formulation and pharmacokinetics of Lazaroid U-74389G (LAZ) liposomes in rats
Authors: Fady Makram L. Ibrahim, Pamela New, Diana S-L Chow
Journal: Cancer Research (2010)

Abstract Purpose Lazaroid U74389G (LAZ) is a 21-aminosteroid that has a radioprotective and antioxidant effects. It prevents the damage in the tissues after radiation by a selective action on vascular endothelium cells in normal tissues. The aim of this study is to develop liposomal formulations of LAZ with favorable pharmacokinetic (PK) profiles for potential therapeutic merits in an animal model. Methods Conventional (LipoB) and pegylated (LipoG) liposomes were prepared with various phosphatidylcholine: cholesterol ratios and lipid: LAZ ratio of 10:1. The liposomes were characterized with the size, charge and release profile. The PK study was performed in Sprague-Dawley rats. The rats were randomized into 3 groups (n=4 each) prior to the dosing of the formulations (LAZ solution, LipoB and LipoG) at a dose of 1 mg/kg by injection through the cannula at jugular veins. At pre-determined time points, blood samples were collected from the tail vein. The LAZ concentrations in plasma were quantified by a validated UPLC/MS/MS assay using Daidazine as the internal standard, with a lower limit of quantification (LLOQ) of 4 ng/ml for LAZ. The PK profiles were constructed by plotting the plasma concentration versus time and the PK parameters were derived using compartmental models of WinNonlin Ver 3.3 software. Results The liposomal preparations with the least amount of cholesterol had the lowest Encapsulation Efficiency (EE=26%). However, an increase of cholesterol ratio up to 20% increased the EE up to 58%. The size of the liposomes was in the range of 90-118 nm. In in-vivo study, the plasma profile of the solution fits 1-compartment model while the liposomal formulations fit 2-compartment model. The solution group yielded a higher Cmax and faster clearance (4.27 μg/ml and 546 ml/hr) than those of LipoB and LipoG (0.97 and 2.03 μg/ml and 380 and 216 ml/hr, respectively). The t1/2's of LAZ from LipoB and LipoG were 5 folds of that from the solution (0.64 and 0.52 hr vs 0.10hr). The solution showed a significantly smaller AUC compared to those of LipoB and LipoG (0.56 μg.hr/ml vs. 0.79 and 1.42 μg.hr/ml, respectively). The volume of distribution was small for the solution compared to LipoB and LipoG (73 ml vs. 1173 and 589 ml, respectively). The half-lives of distribution and elimination, t1/2 α and t1/2 β, were comparable between LipoB and LipoG (0.22 vs. 0.16 hr and 3.17 vs. 2.55 hr, respectively). Conclusion The liposomal formulations modified the pharmacokinetics of LAZ solution. The liposomal formulations resulted in a slower clearance and wider distribution of LAZ in-vivo compared to the solution. LAZ systemic exposures in rats after administration of LAZ liposomes were 1.4 −2.5 folds higher than that of solution. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2652.
Different biological significance of sCD14 and LPS in HIV-infection: Importance of the immunovirology stage and association with HIV-disease progression markers
Authors: MaConcepción Romero-Sánchez, Alejandro González-Serna, Yolanda M. Pacheco, Sara Ferrando-Martínez, Kawthar Machmach, María García-García, Ana Isabel Álvarez-Ríos, Francisco Vidal, Manuel Leal, Ezequiel Ruiz-Mateos
Journal: Journal of Infection (2012)
Establishment of an animal model of ovalbumin sensitised mouse to study protein induced enteropathy.
Authors: C Malo, C L Morin
Journal: Gut (1986)

<h3>Abstract</h3> CodB is a cytosine transporter from the Nucleobase-Cation-Symport-1 (NCS1) transporter family, a member of the widespread LeuT superfamily. Previous experiments with the nosocomial pathogen <i>Pseudomonas aeruginosa</i> have shown CodB also to be important in the uptake of 5-fluorocytosine, which has been suggested as a novel drug to combat antimicrobial resistance by suppressing virulence in the organism. Here we solve the crystal structure of CodB from <i>Proteus vulgaris</i>, at 2.4Å resolution in complex with cytosine. We show that the protein carries out the sodium-dependent uptake of cytosine and can bind 5-fluorocytosine. Comparison of the substrate-bound structures of CodB and the hydantoin transporter Mhp1, the only other NCS1 family member for which the structure is known, highlight the importance of the hydrogen bonds that the substrates make with the main chain at the breakpoint in the discontinuous helix, TM6. In contrast to other LeuT superfamily members, neither CodB nor Mhp1 make specific interactions with residues on TM1. Comparison of the structures provides insight into the intricate mechanisms of how these proteins transport substrates across the plasma membrane.