tbuckley/cabot-search huggingface dataset:
Fluctuations of calcium, phosphorus, sodium, potassium, and chlorine in single alpha and beta cells during glucose perifusion of rat islets.
Authors: R K Kalkhoff, K A Siegesmund
Journal: Journal of Clinical Investigation (1981)

To study the relationship between islet hormonal secretion and intracellular content of five elements, a rat islet perifusion technique was used in 24 paired experiments. Control and experimental chambers each containing 100 islets, received 2.8 and 16.7 mM D-glucose, respectively. Effluent was collected frequently for hormone measurements. At eight different time intervals form 0--30 min islets were fixed and prepared for scanning electron microscopy. Over 900 unobscured alpha and beta cells were selected by size and shape criteria. Energy dispersive x-ray analysis was applied to each single cell to determine relative content of calcium (Ca), potassium (K), sodium (Na), chlorine (Cl), and phosphorus (P). Experimental chambers exhibited typical acute (0--9 min) and second phase (10--30 min) insulin secretion in association with suppression of glucagon release after 10 min. At 2 min an abrupt upward K spike in both alpha and beta cells was followed at 3--4 min with a 1.5- to 2-fold rise of Ca and a reciprocal decrease in K, Na, Cl, and P. From 3 to 30 min biphasic insulin secretion. Reduced alpha cell calcium after 6 min preceded suppression of glucagon secretion. After 2 min K related inversely to Ca content in both alpha and beta cells. These results could not be reproduced when D-galactose was substituted for D-glucose. We conclude that sequential changes of Ca content that are reciprocally related to K are predictive of beta cell insulin release and suppression of alpha cell glucagon secretion.
Importance of Primary Capture and L-Selectin–Dependent Secondary Capture in Leukocyte Accumulation in Inflammation and Atherosclerosis in Vivo
Authors: Einar E. Eriksson, Xun Xie, Joachim Werr, Peter Thoren, Lennart Lindbom
Journal: The Journal of Experimental Medicine (2001)

In the multistep process of leukocyte extravasation, the mechanisms by which leukocytes establish the initial contact with the endothelium are unclear. In parallel, there is a controversy regarding the role for L-selectin in leukocyte recruitment. Here, using intravital microscopy in the mouse, we investigated leukocyte capture from the free flow directly to the endothelium (primary capture), and capture mediated through interactions with rolling leukocytes (secondary capture) in venules, in cytokine-stimulated arterial vessels, and on atherosclerotic lesions in the aorta. Capture was more prominent in arterial vessels compared with venules. In venules, the incidence of capture increased with increasing vessel diameter and wall shear rate. Secondary capture required a minimum rolling leukocyte flux and contributed by ∼20–50% of total capture in all studied vessel types. In arteries, secondary capture induced formation of clusters and strings of rolling leukocytes. Function inhibition of L-selectin blocked secondary capture and thereby decreased the flux of rolling leukocytes in arterial vessels and in large (&amp;gt;45 μm in diameter), but not small (&amp;lt;45 μm), venules. These findings demonstrate the importance of leukocyte capture from the free flow in vivo. The different impact of blockage of secondary capture in venules of distinct diameter range, rolling flux, and wall shear rate provides explanations for the controversy regarding the role of L-selectin in various situations of leukocyte recruitment. What is more, secondary capture occurs on atherosclerotic lesions, a fact that provides the first evidence for roles of L-selectin in leukocyte accumulation in atherogenesis.
Discussions About Clinical Trials Among Patients With Newly Diagnosed Lung and Colorectal Cancer
Authors: Anneke T. Schroen, Craig L. Slingluff
Journal: JNCI Journal of the National Cancer Institute (2014)

Clinical trial enrollment among adult cancer patients in the United States is low and presents a major impediment to the advancement of cancer care and prevention. Fewer than 5% of adult cancer patients in the United States are estimated to participate in National Cancer Institute (NCI)–sponsored clinical research trials, a statistic that has been stagnant for decades (1–4). Furthermore, certain subsets of the US population, including the elderly, racial or ethnic minorities, and women, have historically been underrepresented in clinical trials (3). Underrepresentation by these groups does not reflect the heterogeneity of the US population or of cancer biology. This shortcoming of the clinical trial enterprise implies inequitable access to clinical trials, threatens the generalizability of trial results, and hinders meaningful subgroup analyses. Concomitantly, many clinical trials close with accrual insufficient to answer their scientific questions. Among phase III trials sponsored by NCI-sponsored clinical trial cooperative groups, 34% closed with insufficient accrual to address the trials’ primary endpoint (5). Furthermore, the Institute of Medicine (IOM) report “A National Cancer Clinical Trials System for the 21st Century:
Potential for Targeting the Fibroblast Growth Factor Receptors in Breast Cancer
Authors: Nancy E. Hynes, Julien H. Dey
Journal: Cancer Research (2010)

Breast cancer is the most common cancer of women, accounting yearly for approximately 30% of newly diagnosed cases and ranking second as a cause of death. Despite improvements in breast cancer detection and development of new therapeutic approaches, there are still tumors for which no targeted therapies are available. This review summarizes recent findings on the fibroblast growth factor receptors (FGFR) and the data supporting their role in breast cancer. We will describe the approaches being made to develop therapeutics targeting these receptors. Finally, to improve the chances for success with FGFR signal transduction inhibitors, strategies to choose appropriate breast cancer patients for treatment will be discussed.
Common Principles of Motor Control in Vertebrates and Invertebrates
Authors: K G Pearson
Journal: Annual Review of Neuroscience (1993)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Missing endomysial and reticulin binding of coeliac antibodies in transglutaminase 2 knockout tissues
Authors: I R Korponay-Szabo
Journal: Gut (2003)

<b>Background:</b> Autoantibodies against transglutaminase 2 (TG2) are thought to be responsible for the endomysial (EMA), reticulin (ARA), and jejunal antibody (JEA) tissue binding of serum samples from coeliac patients but the exclusive role of TG2 in these staining patterns has not yet been established. <b>Aims:</b> To evaluate whether antigens other than TG2 contribute to EMA/ARA/JEA reactions. <b>Patients:</b> Serum samples from 61 EMA/ARA/JEA positive untreated patients with coeliac disease, 40 dermatitis herpetiformis patients, and 34 EMA/ARA/JEA negative non-coeliac controls were tested. <b>Methods:</b> TG2 knockout (TG2−/−) and wild-type mouse oesophagus, jejunum, liver, and kidney sections, and TG2−/− sections coated with human recombinant TG2 were used as substrates in single and double immunofluorescent studies for patient IgA binding and tissue localisation of TG2, fibronectin, actin, and calreticulin. <b>Results:</b> None of the patient serum samples elicited EMA, ARA, or JEA binding in TG2−/− morphologically normal tissues. In contrast, 96 of 101 gluten sensitive patient samples (95%) reacted with wild-type mouse tissues and all 101 reacted in EMA/ARA/JEA patterns with TG2−/− mouse tissues coated with human TG2. Serum IgA binding to TG2−/− smooth muscle cells was observed in low titres in 31.1%, 27.5%, and 20.5%, and to TG2−/− epithelium in 26.3%, 5.0%, and 8.8% of coeliac, dermatitis herpetiformis, and control samples, respectively. These positivities partly colocalised with actin and calreticulin but not with TG2 or fibronectin. <b>Conclusions:</b> EMA/ARA/JEA antibody binding patterns are exclusively TG2 dependent both in coeliac and dermatitis herpetiformis patients. Actin antibodies are responsible for some positivities which are not part of the EMA/ARA/JEA reactions.
Comparison between positron emission tomography using 2-[fluorine-18]fluoro-2-deoxy-D-glucose, conventional imaging and computed tomography for staging of breast cancer
Authors: S. Mahner, S. Schirrmacher, W. Brenner, L. Jenicke, C.R. Habermann, N. Avril, J. Dose-Schwarz
Journal: Annals of Oncology (2008)
ZNF300P1 Encodes a lincRNA that regulates cell polarity and is epigenetically silenced in type II epithelial ovarian cancer
Authors: Brian Gloss, Kim Moran-Jones, Vita Lin, Maria Gonzalez, James Scurry, Neville F Hacker, Robert L Sutherland, Susan J Clark, Goli Samimi
Journal: Molecular Cancer (2014)

Abstract Background We previously identified that the CpG island-associated promoter of the novel lincRNA ZNF300P1 (also known as LOC134466 ) is frequently hypermethylated and silenced in ovarian cancer tissues. However, the function of ZNF300P1 was unknown. In this report we demonstrate that ZNF300P1 is involved in the regulation of key cell cycle and cell motility networks in human ovarian surface epithelial cells, and may play a role in promoting metastasis in ovarian cancer cells. Methods We applied methylated DNA immunoprecipitation on whole genome promoter tiling arrays and Sequenom assays to examine methylation status of ZNF300P1 in multiple ovarian cancer cell lines, as well as in normal ovarian and ovarian tumor tissues. Transcript profiling was used to investigate the effects of ZNF300P1 suppression in ovarian cancer cells. We utilized siRNA knockdown in normal ovarian surface epithelial cells and performed cellular proliferation, migration and adhesion assays to validate and explore the profiling results. Results We demonstrate that ZNF300P1 is methylated in multiple ovarian cancer cell lines. Loss of ZNF300P1 results in decreased cell proliferation and colony formation. In addition, knockdown of the ZNF300P1 transcript results in aberrant and less persistent migration in wound healing assays due to a loss of cellular polarity. Using an ex vivo peritoneal adhesion assay, we also reveal a role for ZNF300P1 in the attachment of ovarian cancer cells to peritoneal membranes, indicating a potential function of ZNF300P1 expression in metastasis of ovarian cancer cells to sites within the peritoneal cavity. Conclusion Our findings further support ZNF300P1 as frequently methylated in ovarian cancer and reveal a novel function for ZNF300P1 lincRNA expression in regulating cell polarity, motility, and adhesion and loss of expression may contribute to the metastatic potential of ovarian cancer cells.
Phase II Study of Carboplatin and Paclitaxel in Advanced Thymoma and Thymic Carcinoma
Authors: Girum L. Lemma, Ju-Whei Lee, Seena C. Aisner, Corey J. Langer, William J. Tester, David H. Johnson, Patrick J. Loehrer
Journal: Journal of Clinical Oncology (2011)

The purpose of this study was to evaluate the impact of carboplatin and paclitaxel in patients with advanced previously untreated thymoma and thymic carcinoma.We conducted a prospective multicenter study in patients with unresectable thymoma (n = 21) or thymic carcinoma (n = 23). Patients were treated with carboplatin (area under the curve, 6) plus paclitaxel (225 mg/m(2)) every 3 weeks for a maximum of six cycles. The primary end point of this trial was to evaluate the objective response rate.From February 2001 through January 2008, 46 patients were enrolled. Thirteen patients had grade 4 or greater toxicity, mostly neutropenia. Using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria, three complete responses (CRs) and six partial responses (PRs; objective response rate [ORR], 42.9%; 90% CI, 24.5% to 62.8%) were observed in the thymoma cohort; 10 patients had stable disease. For patients with thymic carcinoma, no CRs and five PRs (ORR, 21.7%; 90% CI, 9.0% to 40.4%) were observed; 12 patients had stable disease. Progression-free survival (PFS) was 16.7 (95% CI, 7.2 to 19.8) and 5.0 (95% CI, 3.0 to 8.3) months for thymoma and thymic carcinoma cohorts, respectively. To date, only seven patients (33.3%) with thymoma have died, compared with 16 patients (69.6%) with thymic carcinoma. Median survival time was 20.0 months (95% CI, 5.0 to 43.6 months) for patients with thymic carcinoma, but it has not been reached for patients with thymoma.Carboplatin plus paclitaxel has moderate clinical activity for patients with thymic malignancies, but this seems less than expected with anthracycline-based therapy. Patients with thymic carcinoma have poorer PFS and overall survival than patients with thymoma.
Electrical stimulation of contractile activity accelerates growth of cultured neonatal cardiocytes.
Authors: T B Johnson, R L Kent, B A Bubolz, P J McDermott
Journal: Circulation Research (1994)

An electrical stimulation system was designed to regulate synchronized contractile activity of neonatal rat cardiocytes and to examine the effects of mechanical contraction on cardiocyte growth. Continuous electrical stimulation at a pulse duration of 5 milliseconds and frequency of 3 Hz resulted in a time-dependent accumulation of cell protein that reached 34% above initial values, as measured by the protein-to-DNA ratio. The growth response did not occur using voltage amplitudes that were subthreshold for contraction and was independent of contraction frequencies set at &gt; or = 0.5 Hz. The RNA-to-DNA ratio increased in parallel to cell protein, indicating that the capacity for protein synthesis was enhanced by contraction. Rates of 28S rRNA synthesis were accelerated twofold in contracting cardiocytes. By comparison, protein and RNA accumulation did not occur in electrically stimulated cardiocytes in which contraction was blocked by either 10 mumol/L verapamil or by 5 mmol/L 2,3-butanedione monoxime, an inhibitor of actomyosin crossbridge cycling. Electrical stimulation of cardiocyte contraction did not enhance alpha-cardiac actin or myosin heavy chain (alpha+beta) mRNA transcript levels relative to 28S rRNA during the period of rapid growth that occurred over the first 48 hours. It is concluded that (1) electrical stimulation of contraction accelerates cardiocyte growth and RNA accumulation, (2) mechanical contraction is involved in regulating the growth of electrically stimulated cardiocytes, and (3) the levels of alpha-actin and myosin heavy chain mRNA increase in proportion to rRNA during the growth of contracting cardiocytes.
Prenatal immune priming with helminth infections: parasite‐specific cellular reactivity and Th1 and Th2 cytokine responses in neonates
Authors: D. S. S. Pit, A. M. Polderman, H. Schulz‐key, P. T. Soboslay
Journal: Allergy (2000)

The present investigation aimed to determine to what extent maternal helminth infection primes parasite‐specific cellular responsiveness in neonates. Umbilical cord mononuclear blood cells (UCBC) and peripheral blood mononuclear cells (PBMC) from mothers proliferated in response to mitogenic stimulation with concanavalin A, as well as to bacterial Streptococcus pyogenes ‐derived (streptolysin O) and helminth‐specific antigens of Necator americanus and Onchocerca volvulus. Cellular responses to Echinococcus multilocularis (Em) and Oesophagostomum bifurcum (Oes), helminth parasites not endemic in the study area, were absent (for Em) or very low (for Oes due to antigenic cross‐reactivity). Cellular responsiveness to mitogen and antigens was higher in mothers than in their neonates. Several Th1‐type (IL‐2, IL‐12, and IFN‐γ) and Th2‐type (IL‐5 and IL‐10) cytokines were produced by UCBC from neonates and PBMC from mothers. Low levels of IFN‐γ were elicited by UCBC in response to helminth and bacterial antigens, while secretion of IL‐2 was pronounced and similarly high in neonates and their mothers. Amounts of IL‐5 produced by UCBC in response to bacterial SL‐O and mitogenic stimulation (PHA) were low, but equivalent levels of IL‐5 were induced by intestinal helminth and filaria‐derived antigens in neonates and mothers. A pronounced production of IL‐10 and IL‐12 by UCBC was observed – spontaneous IL‐10 and IL‐12 secretion by UCBC was higher in neonates than by PBMC from mothers. Net amounts of IL‐10 elicited by helminth antigens were similar, while net IL‐12 in response to mitogen, and bacterial and helminth antigens was significantly higher in mothers than their offspring. Our results indicate that human maternal helminth infection does sensitize in utero for parasite‐specific cellular responsiveness in offspring, and also activates specific production of several cytokines, and such children do not present a dominant expression of immunity of either Th1 or Th2.
Thymocytes can become mature T cells without passing through the CD4+ CD8+, double-positive stage.
Authors: C P Liu, J W Kappler, P Marrack
Journal: The Journal of Experimental Medicine (1996)

T cells bearing the class II-restricted, DO-T cell receptor (TCR) are CD4+ if their thymocyte precursors are positively selected on the class II protein, IAd, but they are almost all CD4- after positive selection on a class II for which they have higher avidity, IAb. DO-TCR+ T cells mature in H-2b mice lacking CD4. CD4- DO-TCR+ T cells appear in H-2b mice at the same rate as their CD4+ counterparts appear in H-2d animals, suggesting that the CD4- cells are not the product of some minor pathway of thymocyte development and selection. In H-2b CD4 knock out mice expressing human CD2 under the control of the mouse CD4 promoter, mature DO-TCR+ cells did not express human CD2. These results suggest that the CD4-CD8-, DO-TCR+ mature T cells have developed without ever passing through the equivalent of a CD4+,CD8+ stage. The early expression of alpha/beta receptors (TCRs) on thymocytes in TCR transgenic mice may allow maturation of this type. Passage through the equivalent of the CD4+ CD8+, double-positive stage is not essential for differentiation of thymocytes into mature T cells.
Effect of gluten-free diet on splenic hypofunction of adult coeliac disease.
Authors: G R Corazza, M Frisoni, D Vaira, G Gasbarrini
Journal: Gut (1983)

Splenic function has been serially measured by counting pitted red cells in 15 coeliac patients, before and during a gluten-free diet. The basal percentage values of pitted cells decreased significantly during treatment but no correlation was observed between the duration of the gluten-free diet and the percentage of recovery of splenic function over basal values. Out of six coeliacs with pitted cell values consistent with splenic hypofunction, three showed a total recovery after gluten withdrawal. Our data suggest that, contrary to recent reports, hyposplenism in adult coeliac disease is improved by a gluten-free diet, and that environmental factors may be important in determining and maintaining this complication.
Thrombocytopenic Purpura and Thyroid Disease
Authors: JOSEPH HERMAN
Journal: Annals of Internal Medicine (1980)

Letters and Corrections1 December 1980Thrombocytopenic Purpura and Thyroid DiseaseJOSEPH HERMAN, M.D.JOSEPH HERMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-93-6-934_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The report by Rodgers and Ries (1) of a case of refractory idiopathic thrombocytopenic purpura raises the question of their patient's thryroid status.A review of the literature up to the end of 1977 (2) revealed 49 case reports of an association between thyrotoxicosis and thrombocytopenia. In 37 patients the disorders ran concurrently, and in 29 the connection between the two appeared "primary" in that no drugs capable of inducing thrombocytopenia had been administered before diagnosis and no other diseases were identified. Twenty-two patients were treated for hyperthyroidism, and in 18 the thrombocyte count returned to normal...References1. RODGERSRIES GC. Refractory idiopathic thrombocytopenic purpura. Ann Intern Med. 1980;92:713-4. Letter. LinkGoogle Scholar2. HERMANRESNITZKYFINK JPA. Association between thyrotoxicosis and thrombocytopenia: a case report and review of the literature. Isr J Med Sci. 1978;14:469-75. MedlineGoogle Scholar3. MARSHALLWEISBERGERLEVYBRECKENRIDGE JARR. Coexistent idiopathic thrombocytopenic purpura and hyperthyroidism. Ann Intern Med. 1967;67:411-4. LinkGoogle Scholar1. DOANBOURONCLEWISEMAN CBB. Idiopathic and secondary thrombocytopenic purpura: clinical study and evaluation of 381 cases over a period of 28 years. Ann Intern Med. 1960;53:861-76. LinkGoogle Scholar2. HERMANRESNITZKYFINK JPA. Association between thyrotoxicosis and thrombocytopenia. Isr J Med Sci. 1978;14:469-75. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Kibbutz Tirat Zvi, Mobile Post 10815; Bisan Valley, Israel PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByThyroid Disease in Patients with Idiopathic Thrombocytopenia: A Cohort StudyFamilial association of autoimmune thrombocytopenia and hyperthyroidism8 Autoimmune thrombocytopeniasNeonatal Thrombocytopenia 1 December 1980Volume 93, Issue 6Page: 934-934KeywordsDrugsHyperthyroidismIdiopathic thrombocytopenic purpuraThyroid diseases Issue Published: 1 December 1980 PDF DownloadLoading ...
Muslim customs surrounding death, bereavement, postmortem examinations, and organ transplants
Authors: A R Gatrad
Journal: BMJ (1994)

Muslims are always buried, never cremated. It is a religious requirement that the body be ritually washed and draped before burial, which should be as soon as possible after death. Those carrying out this duty should be immunised against hepatitis B and be aware of the hazards of AIDS. Muslim women never attend burials and it is rare for funeral directors to be involved. Muslim jurists from the Arab world can justify organ transplantation, but those from the Indian subcontinent are against it. They are united in the belief of the sacredness of the human body and thus deplore postmortem examinations.
Chronic diarrhoea after radiotherapy for gynaecological cancer: occurrence and aetiology.
Authors: A Danielsson, H Nyhlin, H Persson, U Stendahl, R Stenling, O Suhr
Journal: Gut (1991)

The occurrence of chronic diarrhoea was evaluated in 173 consecutive patients previously treated with radiation for gynaecological cancer. A survey of gastrointestinal symptoms showed a high frequency of diarrhoea; 13% of the patients had 21 or more bowel movements a week and 3% had 28 or more. Significantly more patients who had a cholecystectomy were in the group with diarrhoea (chi 2 = 6.26; p less than 0.02). Twenty patients with chronic or intermittent diarrhoea were subject to extended gastrointestinal investigation. Bile acid malabsorption was evaluated by the 75Selenahomocholic acid-taurine test (SeHCAT). Bile acid malabsorption was found in 13 (65%) of the 20 patients further investigated, of whom seven had extremely low whole body retention values, which is consistent with severe malabsorption. The results suggest that bile acid malabsorption is a common cause of diarrhoea after radiation treatment for gynaecological cancer. Bacterial contamination was diagnosed in nine patients (45%) by the [14C]-D-xylose breath test or by the cholyl-[14C]-glycine breath test in combination with a normal test for bile acid malabsorption. All patients with vitamin B-12 deficiency, who were tested for bile acid malabsorption, had low retention times for the SeHCAT (p = 0.05). A significant decline in the frequency of diarrhoea was found after treatment with antibiotics or bile acid sequestrants, or both, in combination with a reduced fat diet.