tbuckley/cabot-search huggingface dataset:
Changes in the expression of intestinal iron transport and hepatic regulatory molecules explain the enhanced iron absorption associated with pregnancy in the rat
Authors: K N Millard
Journal: Gut (2004)

<b>Background:</b> Iron absorption increases during pregnancy to cater for the increased iron requirements of the growing fetus. <b>Aims:</b> To investigate the role of the duodenal iron transport molecules and hepatic regulatory molecules in coordinating the changes in iron absorption observed during pregnancy. <b>Methods:</b> Rats at various days of gestation and 24–48 hours post-partum were examined for hepatic expression of hepcidin, transferrin receptors 1 and 2, and HFE (the gene mutated in the most prevalent form of hereditary haemochromatosis), and duodenal expression of divalent metal transporter 1 (DMT1), duodenal cytochrome b (Dcytb), iron regulated mRNA (Ireg1), and hephaestin (Hp) by ribonuclease protection assay, western blotting, and immunohistochemistry. <b>Results:</b> Decreased hepatic non-haem iron and transferrin saturation and increased expression of <i>transferrin receptor 1</i> in the liver indicated a progressive reduction in maternal body iron stores during pregnancy. Duodenal expression of the iron transport molecules DMT1, Dcytb, and Ireg1 increased during pregnancy, and this corresponded with a reduction in <i>hepcidin</i>, <i>HFE</i>, and <i>transferrin receptor 2</i> expression in the liver. Expression of all molecules returned towards control values by 24–48 hours post-partum. <b>Conclusions:</b> These data indicate that increased expression of key iron transport molecules is responsible for the elevated iron absorption associated with pregnancy, and implicate hepcidin, HFE, and transferrin receptor 2 in determining how the maternal iron homeostatic machinery responds to the increased iron demands accompanying gestation.
Contraceptives, counselling, and pregnancy in women with sickle cell disease.
Authors: R J Howard, C Lillis, S M Tuck
Journal: BMJ (1993)

Sickle cell disease is listed in the manufacturers9 data sheets in the United Kingdom as a contraindication to the use of most combined contraceptive pills; the result is confused advice on family planning to a group of women who are at substantial risk from both planned and unplanned pregnancy. A study in north London on the use of contraceptives by women with sickle cell disease indicates that the use of combined oral contraceptives is common. Although medical staff usually advised against pregnancy, such advice was almost always ignored. Over half of the women surveyed had some knowledge about antenatal diagnosis. Family planning advice should be an integral part of the care of women with sickle cell disease. In the absence of specific data to the contrary all methods of contraception may be considered, although with appropriate caution.
Spain votes to ban smoking in public places
Authors: A. G. Rada
Journal: BMJ (2010)

The Spanish lower house of parliament, the Congress of Deputies, voted on 21 December to ban smoking in all enclosed public places in Spain from 2 January. The new law also bans smoking in children’s parks and outside hospitals and schools, although some areas of psychiatric institutions and prisons are exempt.

The decision brings to an end the “Spanish model” of permissive smoking legislation that the tobacco lobby in Spain has been defending ( BMJ 2010;341:c5983, doi: 10.1136/bmj.c5983; BMJ 2010;341:c6462; doi: 10.1136/bmj.c6462). According to public health experts loopholes in the …
Local delivery of evans blue significantly prevents in-stent restenosis in patients with acute myocardial infarction
Authors: Yoshiharu Fujimori, Hiroshi Morio, Kuniko Terasawa, Takashi Shiga, Masaru Hatano, Masaaki Osegawa, Yasumi Uchida, Toshihiro Morita
Journal: Journal of the American College of Cardiology (2002)
SPLEEN CELL PROLIFERATION IN RESPONSE TO HOMOLOGOUS ANTIGENS STUDIED IN CONGENIC RESISTANT STRAINS OF MICE
Authors: Richard W. Dutton
Journal: The Journal of Experimental Medicine (1966)

The proliferative responses obtained when spleen cell suspensions from two different inbred strains of mice were mixed were investigated further using congenic resistant strain pairs. Strong responses were obtained in 9 cases out of 12 where the two strains differed at a single gene locus controlling an H-2 histocompatibility antigen. No responses were obtained where the difference occurred at loci controlling weak histocompatibility antigens. These findings have been taken to provide additional circumstantial evidence that the response represents an in vitro homograft reaction to homologous tissue antigens.
Transforming Growth Factor-β1 Is a Molecular Target for the Peroxisome Proliferator-Activated Receptor δ
Authors: Hyo Jung Kim, Sun Ah Ham, Sung Uk Kim, Jin-Yong Hwang, Jae-Hwan Kim, Ki Churl Chang, Chihiro Yabe-Nishimura, Jin-Hoi Kim, Han Geuk Seo
Journal: Circulation Research (2007)

The peroxisome proliferator-activated receptor (PPAR)delta has been implicated in the pathogenesis of atherogenic disorders. However, its physiological roles and functions in vascular smooth muscle cells (VSMCs) remain relatively unclear. In the present study, we show that the gene encoding transforming growth factor (TGF)-beta1 is a PPARdelta target in VSMCs. The PPARdelta activator GW501516 upregulates TGF-beta1 expression in a dose- and time-dependent manner. This induction is attenuated significantly by the presence of small interfering RNA against PPARdelta or GW9662, an inhibitor of PPARdelta. Furthermore, activated PPARdelta induces TGF-beta1 promoter activity by binding to the direct repeat-1 response element TGF-beta1-direct repeat-1. Mutations in the 5' or 3' half-sites of the response element totally abrogate transcriptional activation and PPARdelta binding, which suggests that this site is a novel type of PPARdelta response element. In addition, ligand-activated PPARdelta attenuated the promoter activity and expression of monocyte chemoattractant protein-1 induced by interleukin-1beta. These effects were significantly reduced in the presence of small interfering RNA against PPARdelta, anti-TGF-beta1 antibody, or a TGF-beta type I receptor inhibitor. Decreased monocyte chemoattractant protein-1 expression induced by PPARdelta was mediated by the effector of TGF-beta1, Smad3. Finally, administration of GW501516 to mice upregulated TGF-beta1, whereas the expression of proinflammatory genes including monocyte chemoattractant protein-1 was significantly attenuated in the thoracic aorta. Taken together, these results demonstrate the presence of a novel TGF-beta1-mediated pathway in the antiinflammatory activities of PPARdelta.
The soluble intracellular domain of megalin does not affect renal proximal tubular function in vivo
Authors: Annabel Christ, Sara Terryn, Vanessa Schmidt, Erik I. Christensen, Matthew R. Huska, Miguel A. Andrade-Navarro, Norbert Hübner, Olivier Devuyst, Annette Hammes, Thomas E. Willnow
Journal: Kidney International (2010)
Identifying the Target Population for Primary Prevention
Authors: Michael M Engelgau, K.M. Venkat Narayan, Frank Vinicor
Journal: Diabetes Care (2002)

Compelling evidence now exists that type 2 diabetes can be prevented or delayed in subjects with impaired glucose tolerance (IGT) (2-h oral glucose tolerance test [OGTT] 140–199 mg/dl) (1–4), a group at great risk for subsequent diabetes and cardiovascular disease (5,6). This evidence has held consistently across different populations, in different countries, among men and women, and in all age and racial and ethnic groups. Based on these studies, national health organizations, including those in the U.S. and Finland, are now calling for action (7,8). The American Diabetes Association (ADA) has recommended to consider clinic-based (opportunistic) screening for prediabetes (impaired fasting glucose [IFG] 110–125 mg/dl or IGT) among persons aged >45 years and among younger persons with other diabetes risk factors; they strongly recommend opportunistic screening in persons aged >45 years with BMI ≥25 kg/m2 (7). Approximately one-third of individuals with either IFG or IGT and two-thirds of individuals with both will develop extant diabetes within 6 years (5). However, at present we know little about validated strategies to detect prediabetes in the “real world.” Using fasting, random, and postprandial glucose measurements or A1C levels are options. Anecdotally, performing glucose challenges is cumbersome, difficult, more costly, time consuming, and less acceptable to both patients and health care providers than fasting glucose or A1C measurements. Thus, our first clinical and public health challenge for primary prevention is clear: how are we going to find people with prediabetes?

The study of Saydah et al. …
Chronic Active Hepatitis Associated with Trazodone Therapy
Authors: Paul L. Beck
Journal: Annals of Internal Medicine (1993)

Trazodone is a widely used nontricyclic antidepressant agent that has been commercially available in North America for more than 10 years. There have been three previously reported cases of trazodone-induced hepatic injury, all of which resolved within 4 to 24 weeks after cessation of the drug. We report the first documented case of trazodone-induced chronic active hepatitis. The patient developed jaundice 8 months after beginning therapy with the drug. Her liver enzymes were markedly elevated, and mild portal hypertension was present at transjugular liver biopsy. The biopsy specimen showed a pattern consistent with chronic active hepatitis. Investigations of other possible causes of chronic active hepatitis were negative, and serum transaminase enzyme levels rapidly returned to normal after withdrawal of trazodone. We suggest that physicians be alert to the possibility of hepatic injury in patients receiving trazodone.
PUVA treatment of scleromyxoedema
Authors: P.M. FARR, F.A. IVE
Journal: British Journal of Dermatology (1984)

Journal Article PUVA treatment of scleromyxoedema Get access P.M. FARR, P.M. FARR Department of Dermatology, Dryburn Hospital, Durham Search for other works by this author on: Oxford Academic Google Scholar F.A. IVE F.A. IVE Department of Dermatology, Dryburn Hospital, Durham Dr F.A. Ive, Department of Dermatology, Dryburn Hospital, Durham DHi5TW. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 110, Issue 3, 1 March 1984, Pages 347–350, https://doi.org/10.1111/j.1365-2133.1984.tb04642.x Published: 01 March 1984 Article history Accepted: 15 August 1983 Published: 01 March 1984
Cardiovascular Response of the Anesthetized Hamster to Reserpine and Ganglionic Blockade
Authors: ROBERT A. MAXWELL, SAMUEL D. Ross, ALBERT J. PLUMMER
Journal: Circulation Research (1957)

The changes produced by reserpine and the ganglionic blocking agent, chlorisondamine chloride on the blood pressure, peripheral flow and blood vessel caliber of the hamster have been studied in an attempt to determine the first cause of the hypotensive effect of these compounds.
Osmolar regulation of endothelin signaling in rat renal medullary interstitial cells.
Authors: M A Vernace, P F Mento, M E Maita, E P Girardi, M D Chang, E P Nord, B M Wilkes
Journal: Journal of Clinical Investigation (1995)

We tested the hypothesis that endothelin (ET) responsiveness in the renal medulla is modulated by ambient osmolarity. Cultured renal medullary interstitial cells (RMICs) were incubated from 3 to 24 h in isosmolar culture medium (300 mOsm/kg H2O) or media rendered hyperosmolar (600 mOsm/kg H2O) by the addition of urea. Under hyperosmolar conditions, the peak of ET-evoked Ca2+ transient was blunted by 45-58% (P < 0.02) and PGE2 accumulation decreased from 16- to 2-fold above basal values (P < 0.001). To explore whether hyperosmolar conditions blunt intracellular signaling via modulation of receptor number or expression, kinetics of ET binding and Northern blot analysis of ETA receptor mRNA was performed. Under hyperosmolar conditions, ETA receptor density was reduced by 84% versus isosmolar conditions (238 +/- 12 vs. 1450 +/- 184 fmol/mg) (P < 0.01). In contrast to the ligand binding studies, ETA receptor mRNA was increased by 58% (P < 0.05) in cells grown under hyperosmolar versus isosmolar media. These observations indicate that in the hyperosmolar setting, ET-evoked intracellular signaling is blunted in RMICs due to ET receptor downregulation. Since ETA receptor mRNA is increased under hyperosmolar conditions, we conclude that ET receptor downregulation is the consequence of either decreased translation of message, increased degradation of receptor peptide, or increased internalization of specific receptor sites.
Larvae of a Dipterous Insect (Antho-Myia Canicularis or Scalaris) Passed Alive in Swarms from the Bowel of a Man
Authors: J. Finlayson
Journal: BMJ (1889)

addition to these, though much less numerous, are observed small, white, glazed, atrophic areas, mostly surrounded by a zone of dilated capillaries.These are very irregular in shape, and vary in size from that of a split-pea to that of the finger nail.Lastly, a few small, rounded nodules are scattered over the face.These are very distinctly elevated, and have a diameter of from one to two lines.Some of them are papular in character, while others have ulcerated, and are more or less covered with crusts.The largest and most striking of these little growths appeared upon the inner side of the left eyeball, and was removed by Dr. Reid.It soon, however, reappeared, extended rapidly, and destroyed the eyesight.
New German law bans genetic tests of fetuses for adult illnesses
Authors: A. Tuffs
Journal: BMJ (2009)

After 10 years of debate the German parliament has passed a strict law aimed at preventing misuse of genetic tests. 

“[The] purpose of the law is to protect individuals from discrimination because of their genetic constitution,” said the health minister, Ulla Schmidt, last Friday in Berlin.

The law limits the use of genetic testing on a fetus to purely medical purposes. Parents are not allowed …
Abstract 1992: Y-box protein-associated acidic protein promotes breast cancer progression and is a potential molecular target
Authors: Olivia J. Scully, Aye Aye Thike, George Wai-Cheong Yip, Puay Hoon Tan, Ken Matsumoto, Boon Huat Bay
Journal: Cancer Research (2014)

Abstract The Y-Box protein- associated acidic protein (YBAP1), also known as Complement component 1, q subcomponent binding protein, is a multifunctional protein which is involved in in the regulation of complement activation, pre-mRNA splicing and mitochondrial function. As YBAP1 has been implicated in tumorigenesis, this study evaluates its role in breast cancer metastasis. YBAP1 mRNA expression was analysed by quantitative real time RT-PCR and YBAP1 protein by Western blot, immunocytochemical and immunofluorescence staining in a panel of breast cancer cell lines. Down-regulation of the YBAP1 gene in MDA-MB-231 breast cancer cells was performed by siRNA-mediated silencing and overexpression of the gene by transfection with the pCI-neo-YBAP1 plasmid, before analysis of the effects on cell migration and invasion. YBAP1 gene profiling was also performed in samples from the commercially available TissueScan Human Breast Cancer Panel 1 (Origene, Rockville, MD). YBAP1 immunohistochemical staining was carried out in breast cancer tissue microarrays constructed from 168 patients diagnosed with invasive ductal breast carcinoma. The YBAP1 immunostaining was performed using rabbit polyclonal anti-YBAP1 (RIKEN) at a dilution of 1:500. The percentage and intensity of YBAP1 immunopositive staining in malignant epithelial cells were recorded. YBAP1 was observed to be expressed in all the breast cancer cell lines (MCF-7, ZR-75, T47D and MDA-MB-231) examined. The protein was observed to be localized in the cytoplasm of breast cancer cells. Overexpression of YBAP1 increased cell migration and invasion in the highly malignant MDA-MB-231 breast cancer cells. Conversely silencing of the YBAP1 gene had the opposite effect, resulting in reduced cell migration and invasion. YBAP1 gene expression was also found to be up-regulated in the more advanced stages of breast cancer (grouped as Stage 0, I and IIa and compared with Stage II b, IIIa and IIIc; P &amp;lt;0.05). For the tissue microarrays, a positive correlation was observed between YBAP1 immunostaining and axillary lymph node status. YBAP1 augments the spread of breast cancer by enhancing cell migration and invasion. Hence, YBAP1 is a potential metastatic biomarker and targeting YBAP1 could be a strategy to combat breast cancer metastasis. Citation Format: Olivia J. Scully, Aye Aye Thike, George Wai-Cheong Yip, Puay Hoon Tan, Ken Matsumoto, Boon Huat Bay. Y-box protein-associated acidic protein promotes breast cancer progression and is a potential molecular target. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1992. doi:10.1158/1538-7445.AM2014-1992
Carcinoma of Third Part of Duodenum
Authors: R. W. Hendry, R. I. Lewis
Journal: BMJ (1955)

<h3>Abstract</h3> Cleavage of Notch by the major intramembrane aspartyl protease complex γ-secretase is a central event in cell regulation and is also important to Alzheimer’s disease, with more than 200 mutations in the catalytic subunit of γ-secretase (PS1) causing severe early-onset forms of the disease. Recently, cryogenic electron microscopy (cryo-EM) has revealed the electron density of the protein-Notch complex in frozen solution, indicating major changes upon substrate binding and a possible helix unwinding to expose peptide bonds. In order understand the all-atom dynamics that cause this process, and to test the Notch binding in a membrane protein rather than solution, we developed an all-atom model of mature wild-type γ-secretase bound to Notch in a complete membrane-water system and studied the system using three independent 500-nanosecond molecular dynamics simulations. Our ensembles are in essential agreement with known cryo-EM data. As in previous simulations we find unusual β-strand transitions in exposed parts of PS1. We also observe the atomic helix motions that cause loss of helicity in bound Notch by direct comparison to corresponding 500 ns simulations of free Notch, in particular five residues to the N-terminal site of the primary cleavage site. Most importantly, we identify three conformation states, with two of them differing in the Notch-bound catalytic site. These dynamics produce a ping-pong relationship of positioning the S3 cleavage sites of Notch relative to the aspartates. These conformation states are not visible in the cryo-EM data; probably the density is an average snapshot of the two states. Our identified conformation states rationalize how Notch cleavage can be imprecise and yield multiple products. Our identified conformation states may aid efforts to develop conformation-selective drugs that target C99 and Notch cleavage differently. <h3>Statement of Significance</h3> The atomic dynamics underlying cleavage of Notch by γ-secretase in the membrane is of major biological importance. Electron microscopy has revealed the protein-Notch complex in frozen solution, showing major changes upon substrate binding and helix unwinding to expose peptide bonds, but does not explain why substrate cleavage is imprecise and produces several products. Our model of wild-type γ-secretase bound to Notch in a complete membrane-water system equilibrated by 3 × 500 nanoseconds of molecular dynamics strongly complements the electron microscopy data: We identify the specific loop and helix motions that cause the β-strand transitions in PS1 and the loss of helicity in specific residues of bound Notch. We identify different conformations of Notch, which importantly affect the S3 cleavage site; the open state may cause the imprecise cleavage with earlier release of products. Our identified states can aid development of conformation-selective drugs that target C99 and Notch cleavage differently.
Immunoglobulin mu-chain gene rearrangement in a patient with T cell acute lymphoblastic leukemia.
Authors: K Ha, M Minden, N Hozumi, E W Gelfand
Journal: Journal of Clinical Investigation (1984)

A 6-yr-old girl with T cell acute lymphoblastic leukemia (ALL) is described. She had a mediastinal mass and her leukemic cells expressed T cell-associated antigens (Leu 1+, OKT3+, OKT9+, and OKT10+). When we examined genomic DNA from the leukemic cells, we detected Ig mu-chain gene rearrangement with germ-line configuration of light chain genes. As reported recently, detecting Ig gene rearrangement has become an important procedure for further classifying B cell precursor cells. This case, however, suggests that there is also heterogeneity among patients with T cell ALL, not only at the level of cell surface phenotypes, but also at the level of the Ig gene. These findings have major implications when we consider both the ontogenesis of these leukemic cells and the normal differentiation of human lymphocytes.
Rheumatoid polyarthritis after rubella.
Authors: J.N McCormick, J.J Duthie, H Gerber, H Hart, S Baker, B.P Marmion
Journal: Annals of the Rheumatic Diseases (1978)

A 21-year-old woman developed persistent polyarthritis indistinguishable from rheumatoid arthritis after rubella. The arthritis persisted for approximately 30 months and was associated with high levels of antibody to rubella virus and with rheumatoid factor. The antibody titres declined pari passu with clinical improvement which progressed to complete resolution. Fractionation of serial serum specimens showed a substantial and persistent IgM antibody response to rubella virus. Rubella antigen was not demonstrated in the synovial exudate.
Pediatric Oncology: A Treatise for the Clinician
Authors: Ruth Andrea Seeler
Journal: JAMA (1983)

The demand for a compact, readable, yet authoritative text on pediatric oncology is a direct result of the progress causing the transition of pediatric cancer to a chronic disease, rather than a fatal disease. This volume, like its companion<i>Pediatric Hematology-Oncology (JAMA</i>1980;243:1751-1752), fills the need for an up-to-date, well-organized, and informative text. Dr Lanzkowsky has used considerable editorial skill to produce a uniformly high quality of writing with his ten collaborators. This book begins with a general consideration of etiologic factors in childhood malignant neoplasms. The second chapter discusses the general clinical and diagnostic considerations peculiar to childhood malignant neoplasms. The individual chapters devoted to the standard pediatric malignant neoplasms—leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, CNS tumors, neuroblastoma, Wilms' tumor, soft-tissue sarcomas, bone tumor, histiocytosis, and retinoblastoma—are all-encompassing. Each specific tumor is discussed with the usual appropriate workup and differential diagnosis, along with the staging considerations. Particularly helpful are tables
A FACTOR FROM NORMAL TISSUES INHIBITING TUMOR GROWTH
Authors: James B. Murphy, Ernest Sturm
Journal: The Journal of Experimental Medicine (1934)

Extracts of desiccated embryo skin and placenta have been found to exert a definite retarding action on the growth of two transplantable carcinomas of mice, but they were without effect on sarcomas. In tests involving some 828 inoculations of the tumor cells and the extracts, complete suppression of growth occurred in from 55 to 71 per cent of instances, as compared with 21 to 27 per cent in the controls, and where growth was not completely suppressed some retardation was found in practically every instance. To judge from findings in rabbits the inhibitor is not demonstrable in the placenta until the beginning of the second third of pregnancy, reaches its maximum by the last third, but disappears about 2 or 3 days before term. Extracts of fresh placenta are without effect, and no very definite inhibition was noted in extracts of a variety of other desiccated or fresh tissues. The conclusions here reported are based on the results of over 3800 inoculations.