tbuckley/cabot-search huggingface dataset:
Hypertension Increases Connexin43 in a Tissue-Specific Manner
Authors: Jacques-Antoine Haefliger, Einar Castillo, Ge´rard Waeber, Gabriela E. Bergonzelli, Jean-Franc¸ois Aubert, Esther Sutter, Pascal Nicod, Bernard Waeber, Paolo Meda
Journal: Circulation (1997)

Background Connexin43 (Cx43), a membrane protein involved in the control of cell-to-cell communication, is thought to play a role in the contractility of the vascular wall and in the electrical coupling of cardiac myocytes. The aim of this study was to investigate the effects of experimental hypertension on Cx43 expression in rat aorta and heart. Methods and Results Rats were made hypertensive after one renal artery was clipped (two kidney, one-clip renal model) or after the administration of deoxycorticosterone and salt (DOCA-salt model). After 4 weeks, all rats showed a similar increase in intra-arterial mean blood pressure and in the thickness of both the aortic wall and the heart. Northern blot analysis of aorta mRNA and immunolabeling for Cx43 showed that hypertensive rats expressed twice as much Cx43 in aorta as the control animals. In contrast, no difference in Cx43 mRNA or in the immunolabeled protein was observed in heart. Conclusions The results show that rats exhibiting a similar degree of blood pressure elevation, as the result of different mechanisms, feature a comparable increase in Cx43 gene expression, which was observed in the aortic but not in the cardiac muscle. These data suggest that localized mechanical forces induced by hypertension are major tissue-specific regulators of Cx43 expression.
Crackly crisps taste better, costly placebos work better, and fleas jump higher on dogs than cats
Authors: J. H. Tanne
Journal: BMJ (2008)

After the Ig Nobel prizes were announced last week, there were a few less “unknown unknowns.” Donald Rumsfeld, the former US defence secretary who first coined the phrase to describe things we didn’t know that we didn’t know, would have been delighted.

The Ig Nobels, spoofs on the Nobel prizes, are awarded for research “that first makes you laugh, then makes you think.” Many are handed out by genuine Nobel laureates, at a ceremony at Harvard University organised by the Annals of Improbable Research . 

The theme of this year’s ceremony was “redundancy.” It featured redundant opening and closing speeches (“Welcome, welcome” and “Goodbye, goodbye”), two appearances by an imitator of the Republican vice presidential candidate, Sarah Palin, and two demonstrations of sword swallowing by last year’s winner ( BMJ 2007;335:741, doi:10.1136/bmj.39363.414780.DB).

The Oxford scientist Charles Spence won the nutrition prize together with Massimiliano Zampini of the University of Trento, Italy, for a study showing that people believe that crackly crisps are 15% tastier. Professor Spence, head of Oxford’s Cross-Modal Laboratory, told the BMJ that in his study people …
742. Human Artificial Chromosome (HAC) Vector Provides Long-Term Therapeutic Transgene Expression in Normal Human Primary Fibroblasts
Authors: Minoru Kakeda, Masaharu Hiratsuka, Keiko Nagata, Akiko Sano, Kanako Osawa, Motonobu Katoh, Mitsuo Oshimura, Kazuma Tomizuka
Journal: Molecular Therapy (2005)

Top of pageAbstract
Human artificial chromosomes (HACs) are segregating freely from host chromosomes through a set of cell divisions. Accordingly, the host genome is not disrupted and the expression of the transgene could be sustained for a prolonged period without suffering the effects of its surrounding sequence on the host genome. These are the ideal properties required for vectors in gene therapy, and therefore HACs are potentially useful to ensure both safety and duration of gene expression in therapeutic gene delivery. We constructed a novel human chromosome 21-derived HAC (21|[Delta]|pqHAC) vector, which devoid of most expressed genes by telomere truncation at the genomic regions proximal to the centromere in both p and q arms, and inserted human erythropoietin (EPO) gene, which is a growth factor for erythroid cells and widely used for the clinical treatment of anemia in renal insufficiency, into the HAC (EPO-21|[Delta]|pqHAC) as a model of therapeutic transgenes. Although low transfer efficiency of intact HACs to the cells has hampered the studies using normal human primary cells, the major targets for ex vivo gene therapy, we successfully demonstrated the introduction of EPO-21|[Delta]|pqHAC vector into normal primary human fibroblasts (hPFs) with micro cell-mediated chromosome transfer (MMCT). However, the mitotic stability of EPO-21|[Delta]|pqHAC vector in normal hPFs and the growth ability of the resultant hPF clones to obtain graft cells for transplantation remained to be elucidated. Here, we studied the hPF clones harboring the EPO-21|[Delta]|pqHAC vector cytogenetically and demonstrated that the structurally defined, extra artificial chromosome was highly maintained in normal hPFs under non-selective condition at a constant copy number mostly in a single copy per cell without accompanying aberration of host chromosomes. Mitotic-loss rates were determined, and the level of stability of EPO-21|[Delta]|pqHAC vector was comparable with those reported for the other top-down and bottom-up artificial chromosomes in human fibro-sarcoma cell line HT1080 cells. These hPF clones proliferated from a single colony up to 3.8x107 cells and then their growth stopped, suggesting that cell senescence occurred and the introduction of the EPO-21|[Delta]|pqHAC vector did not cause immortalization. We also showed the long-term expression of human epo gene in the hPFs carrying the EPO-21|[Delta]|pqHAC vector. In conclusion, this study shows the potential application of the 21|[Delta]|pqHAC vector in hormone-replacement gene therapy, which might ensure safety with no lesion of host chromosomes and provides long-term therapeutic transgene expression. This also implies that utilization of the HAC vector offers novel options for ex vivo gene therapy.
A Teaching Attachment for Retinoscopy
Authors: Jun Fukuhara, Kevin M. Miller, Charles Vega, David L. Guyton
Journal: Ophthalmology (1987)

A teaching attachment for a conventional streak retinoscope allows a second observer to view the retinoscopic reflex during retinoscopy. The device weighs 200 grams and is attached to the retinoscope by a semi-flexible, rotatable linkage. A beam splitter, one-power telescope, and erecting mirror form a displaced aerial image of the retinoscope peephole for the observer. With identical retinoscopic reflexes observed through the actual peephole and its aerial image, the device can be used to teach basic retinoscopy techniques to new refractionists, or to demonstrate subtle reflexes to more experienced observers.
Clinics in General Practice. A case of right iliac fossa pain.
Authors: W Shannon, J S Price, J C Angell
Journal: BMJ (1977)

The trainee's problemThe patient is a 16-year-old girl and the elder daughter of intensely religious school-teaching parents.She herself has always seemed a fairly happy child and has recently been "converted" to the same beliefs her parents hold-apparently of her own free will and without regret.She attends the local comprehensive school and is making adequate progress.She is hoping to enter nursing, and her parents seem pleased about this.Her medical history was fairly uneventful until about two years ago since when she has had recurring bouts of abdominal pain, sometimes in the centre of the abdomen and colicky, sometimes in the right iliac fossa and more constant.It is difficult to determine any pattern underlying these attacks, which have now produced some eight episodes of consultation.During one episode a year ago she was admitted to hospital as having possible acute appendicitis.Her pain settled quickly, and no operation was needed.No cause for her symptoms was found, and the discharge diagnosis was, perhaps unfortunately, mild acute appendicitis.Two months ago she was again seen at hospital on her own initiative-at a weekend when another practice was covering but was not admitted.I saw her again yesterday with stabbing pain in the right iliac fossa.
Acute Dilatation of Stomach
Authors: R. D. MacRae
Journal: BMJ (1943)

Acute D latation of the StomachA case of this dangerous malady has just occurred in my hospital practice, and may prove of interest with reference to the article by Messrs. Lee and Somerville (1941) and the letter by Dr. Gustav Singer (1941), both in your columns. CASE HISTORYAn otherwise healthy man aged 35 was admitted for pain in the abdomen, vomiting, and constipation.Examination showed marked meteorism, tenderness in the lower abdomen, and a ballooned recLum with fullness in the upper part of the recto-vesical space.Two
“We were treated like adults”—development of a pre-medicine summer school for 16 year olds from deprived socioeconomic backgrounds: action research study
Authors: Trisha Greenhalgh, Jill Russell, Petra Boynton, Frances Lefford, Nikhil Chopra, Lisa Dunkley
Journal: BMJ (2006)

To develop a one week widening access summer school for 16 year old pupils from non-traditional backgrounds who are considering applying to medical school, and to identify its short term impact and key success factors.Action research with partnership schools in deprived inner city areas in five overlapping phases: schools liaison, recruitment of pupils and assessment of needs, programme design, programme delivery, and evaluation. The design phase incorporated findings from one to one interviews with every pupil, and workshops and focus groups for pupils, parents, teachers, medical student assistants, NHS staff, and other stakeholders. An in-depth process evaluation of the summer school was undertaken from the perspective of multiple stakeholders using questionnaires, interviews, focus groups, and observation.40 pupils aged 16 years from socioeconomically deprived and under-represented ethnic minority groups.The summer school was popular with pupils, parents, teachers, and staff. It substantially raised pupils' confidence and motivation to apply to medical school. Critical success factors were identified as an atmosphere of "respect"; a focus on hands-on work in small groups; the input of medical students as role models; and vision and leadership from senior staff. A particularly popular and effective aspect of the course was a grand round held on the last day, in which pupils gave group presentations of real cases.An action research format allowed us to draw the different stakeholders into a collaborative endeavour characterised by enthusiasm, interpersonal support, and mutual respect. The input from pupils to the programme design ensured high engagement and low dropout rates. Hands-on activities in small groups and social drama of preparing and giving a grand round presentation were particularly important.
Upregulation of insulin-like growth factor I gene expression in the lesions of osteoarthritic human articular cartilage.
Authors: J F Middleton, J A Tyler
Journal: Annals of the Rheumatic Diseases (1992)

Expression of insulin-like growth factor I (IGF-I)mRNA and IGF-I protein was studied in human osteoarthritic and young articular cartilage by in situ hybridisation and immunohistochemistry. In situ hybridisation showed that relatively low amounts of IGF-I mRNA signal were present in anatomically normal regions of osteoarthritic and young cartilage. In fibrillated osteoarthritic cartilage, however, the signal intensity was significantly higher than in non-fibrillated cartilage. Particularly high levels of IGF-I mRNA were present in the surface cell clones of more advanced lesions, the amount of signal being about four to five times greater than in anatomically normal cartilage. The amount of message varied with cartilage depth. In young cartilage there was less IGF-I mRNA in the superficial zone than in the middle and deep zones. In fibrillated regions of osteoarthritic joints the amount of message in surface cells was greater than in deeper regions. A specific human IGF-I antibody was used to show the presence intracellularly of IGF-I protein in osteoarthritic and young cartilage. Raised levels of IGF-I message in osteoarthritic chondrocytes may represent an attempt at increased matrix repair, operating by an autocrine/paracrine mechanism.
Outcomes and Long-Term Survival for Patients Undergoing Mitral Valve Repair Versus Replacement
Authors: Vinod H. Thourani, William S. Weintraub, Robert A. Guyton, Ellis L. Jones, Willis H. Williams, Sharif Elkabbani, Joseph M. Craver
Journal: Circulation (2003)

A paucity of literature is available on the effects of age and coronary artery bypass grafting (CABG) on the outcomes of patients undergoing mitral valve (MV) repair versus replacement.A matched study was performed using prospectively collected data from the Emory cardiovascular database from 1984 to 1997 comparing 625 MV repair patients with 625 MV replacement patients. Mean age was significantly higher in the replacement group (56+/-14 versus 55+/-14 years). Preoperative demographics and postoperative outcomes were similar between groups. Length of stay (LOS) was significantly less in the repair group (9.5+/-9.4 versus 12.3+/-13.1 days). In-hospital mortality was significantly less in the repair group (4.3% versus 6.9%), and overall 10-year survival was significantly higher in the repair group (62% versus 46%). Ten-year survival of patients <60 years of age was significantly higher in repair patients (81% versus 55%) but similar in patients > or =60 years of age (33% versus 36%, respectively). Ten-year survival of MV repair without CABG was significantly higher compared with MV replacement patients (74% versus 51%) but similar to patients with concomitant CABG (28% versus 34%, respectively). Independent predictors of long-term mortality included increasing age, urgent/emergent status, female sex, diabetes mellitus, increasing weight, heart failure, decreasing ejection fraction, concomitant CABG, and MV replacement.Mitral valve repair has reduced LOS and improved in-hospital and 10-year survival. However, in the present series, MV repair does not provide significant long-term survival benefit over MV replacement in patients older than 60 years of age or those requiring concomitant CABG.
Cytogenetic Studies in Multiple Myeloma.
Authors: John R. Durant
Journal: Annals of Internal Medicine (1967)

s1 May 1967Cytogenetic Studies in Multiple Myeloma.John R. Durant, M.D., F.A.C.P., Ernest M. Tassoni, M.D.John R. Durant, M.D., F.A.C.P.Search for more papers by this author, Ernest M. Tassoni, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1041_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the past 3 years the bone marrows of 14 patients with unequivocal multiple myeloma were subjected to cytogenetic study. All had at least 20 clear, scorable metaphase plates. Five had a morphologically similar, large, acrocentric marker chromosome whose size was approximately that of the long arms of a B group chromosome present in most of their karyotypable hyperdiploid cells. Two had a similar, but either lightly stained or despiralized, chromosome in the majority of the hyperdiploid cells that were scored. One patient had a large, submetacentric marker present in several of his hyperdiploid metaphase plates. No other consistent abnormality... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1967Volume 66, Issue 5Page: 1041-1041KeywordsBone marrowCellsChromosomesCytogeneticsMultiple myeloma Issue Published: 1 May 1967 PDF downloadLoading ...
Hypogammaglobulinaemia associated with gold therapy.
Authors: T Hunter
Journal: Annals of the Rheumatic Diseases (1985)

A recent review' has suggested that reports of gold salts being inhibitory to adjuvant arthritis following parenteral administration may be explained by counterirritancy.While we cannot completely preclude this possibility, the following points seem relevant.The injection sites were examined daily and no signs of irritation or necrosis were observed, the animals were not distressed, and there were no adverse effects on bodyweight gain.NATM had no effect on the acute indomethacin-sensitive inflammation at day 3, but the secondary arthritis was inhibited in a dosedependent manner, with the activity being maintained for 14 days after cessation of dosing.Finally, the systemic non- inflammatory disease was modified, with NATM reversing the thymic regression and splenic hypertrophy seen in adjuvant arthritic rats.These results are similar to those obtained by Walz et al.,4 who in addition showed a correlation between antiarthritic activity and serum gold levels.It appears that under certain conditions adjuvant-induced arthritis in the rat can be used to evaluate the efficacy of gold salts.
THE RÔLE OF THE "WAX" OF THE TUBERCLE BACILLUS IN ESTABLISHING DELAYED HYPERSENSITIVITY
Authors: Sidney Raffel, John E. Forney
Journal: The Journal of Experimental Medicine (1948)

The purified wax fraction of the tubercle bacillus, which has been previously demonstrated as an essential element in causing delayed tuberculin hypersensitivity in response to the protein of the tubercle bacillus, is now found to have the same activity with regard to a simple chemical antigen, picryl chloride. One injection of this compound with wax intraperitoneally into guinea pigs results in a marked delayed cutaneous hypersensitivity, demonstrable by contact and intracutaneous test, and of long duration. The effect is not related to an adjuvant activity of the wax as defined by ordinary standards. The relationship of these observations to the occurrence of "heteroallergic" phenomena in tuberculosis is discussed. The possibility that the occurrence of spontaneous contact hypersensitivities may depend upon the presence of similarly active lipoidal components of the skin is commented upon.
Toll-Like Receptor 7-Mediated Type I Interferon Signaling Prevents Cholestasis- and Hepatotoxin-Induced Liver Fibrosis
Authors: Yoon Seok Roh, Surim Park, Jong Won Kim, Chae Woong Lim, Ekihiro Seki, Bumseok Kim
Journal: Hepatology (2013)

Toll-like receptor 7 (TLR7) signaling predominantly regulates production of type I interferons (IFNs), which has been suggested in clinical studies to be antifibrotic. However, the mechanistic role of the TLR7-type I IFN axis in liver fibrosis has not been elucidated. In the present study, liver fibrosis was induced in wild-type (WT), TLR7-deficient, and IFN-α/β receptor-1 (IFNAR1)-deficient mice and TLR7-mediated signaling was assessed in liver cells isolated from these mice. TLR7-deficient and IFNAR1-deficient mice were more susceptible to liver fibrosis than WT mice, indicating that TLR7-type I IFN signaling exerts a protective effect against liver fibrosis. Notably, the hepatic expression of interleukin-1 receptor antagonist (IL-1ra) was suppressed in TLR7- or IFNAR1-deficient mice compared with respective WT mice, and treatment with recombinant IL-1ra reduced liver fibrosis. In vivo activation of TLR7 significantly increased IFNa4 and IL-1ra expression in the liver. Interestingly, each cytokine had a different cellular source, showing that dendritic cells (DCs) are the responsible cell type for production of type I IFN, while Kupffer cells (KCs) mainly produce IL-1ra in response to type I IFN. Furthermore, TLR7 activation by R848 injection suppressed liver fibrosis and production of proinflammatory cytokines, and these effects were dependent on type I IFN signaling. Consistent with in vivo data, IFN-α significantly induced IL-1ra production in primary KCs. Conclusion : TLR7 signaling activates DCs to produce type I IFN, which in turn induces antifibrogenic IL-1ra production in KCs. Thus, manipulation of the TLR7-type I IFN-IL-1ra axis may be a new therapeutic strategy for the treatment of liver fibrosis. (Hepatology 2014;60:237–249)
Pulmonary venous atrial systolic flow reversal velocity during ventricular systole predicts left atrial elastance: a new method for assessing left atrial systolic function in an animal model
Authors: Hirotsugu Yamada, Erwan Donal, Nail L. Greenberg, Maureen Martin, Don W. Wallick, Shaowei Zhuang, Youhua Zhang, Todor N. Mazgalev, James D. Thomas, Leonardo Rodriguez
Journal: Journal of the American College of Cardiology (2002)
Effects of ileal resection on biliary lipids and bile acid composition in patients with Crohn's disease.
Authors: A Lapidus, K Einarsson
Journal: Gut (1991)

Biliary lipid composition, cholesterol saturation, and bile acid pattern were determined in fasting duodenal bile of 10 patients (four men and six women, mean age 41 years) with Crohn9s disease and a history of ileal resection (mean 64 cm). The data were compared with corresponding values in a group of healthy subjects. None of the patients with Crohn9s disease had supersaturated bile. Cholesterol saturation was significantly lower in the patients with Crohn9s disease than in the healthy subjects. The molar percentage of cholesterol was also lower among the patients but there was no significant difference. The molar percentages of phospholipids and bile acids were normal. Bile acid composition in the patients with ileal resection was characterised by a significant decrease in the deoxycholic acid fraction and a pronounced increase in the ursodeoxycholic acid fraction compared with the healthy subjects. The surprisingly high percentage of ursodeoxycholic acid may contribute to the low degree of cholesterol saturation in bile. Based on these results patients with Crohn9s disease should not have an increased risk of cholesterol gall stone formation.
Involuntary Weight Loss: Diagnostic and Prognostic Significance
Authors: KEITH I. MARTON
Journal: Annals of Internal Medicine (1981)

We prospectively evaluated 91 patients with involuntary weight loss. Thirty-two (35%) had no identifiable physical cause of weight loss, whereas the remainder had various physical illnesses. During the year after the index visit, 23 (25%) of the patients died and another 14 (15%) deteriorated clinically. Physical causes of weight loss were clinically evident on the initial evaluation in 55 of 59 patients. The four patients in whom the diagnosis was initially missed had cancer, and in only one of these patients was the illness truly occult. Because diagnoses were usually made rapidly in patients with a physical cause of weight loss, we conclude that involuntary weight loss is rarely due to "occult" disease. We developed a decision rule that used six attributes to correctly identify 57 of 59 patients (97%) with a physical cause of weight loss and 23 of 32 patients without. Thus, our rule may help in the early triage of patients with involuntary weight loss.