tbuckley/cabot-search huggingface dataset:
Subclassification of beta-adrenergic receptors in cultured rat cardiac myoblasts and fibroblasts.
Authors: Y H Lau, R B Robinson, M R Rosen, J P Bilezikian
Journal: Circulation Research (1980)

3-Adrenergic receptors in primary cultures of neonatal rat cardiac cells were identified with the radioligand [ l25 I]iodohydroxybenzylpindolol ([ 125 I]IHYP).At the time of cell plating, a differential attachment procedure was employed to separate myocardial (M) cells from fibroblast-like (F) cells.After 3-4 days, the cultures enriched in M cells were still more than 80% pure and the cultures enriched in F cells were more than 95% pure.For binding studies, confluent cell layers were nonenzymatically detached as single cell suspensions.Both M and F cells contained a limited number of fiadrenergic receptors (M, 7600 ± 2100 sites/cell; F, 9000 ± 2400 sites/cell) which had very high affinity (M, K d = 88 ± 33 PM; F, Kd = 71 ± 23 pM) for [ 125 I]IHYP.For each cell type, the binding sites were stereoselective for the /-isomers of agonists and antagonists.Further binding studies on the relative potency of /8-agonists showed that the /{-receptors in M cells could be subclassified as fii (isoproterenol > epinephrine = norepinephrine), whereas the /{-receptors in F cells were more typical of /} 2 (isoproterenol > epinephrine > norepinephrine).The order of potency of these catecholamines in stimulating the adenylate cyclase activity in M and F cells was consistent with the order of potency observed in binding studies.Practolol, a /?i inhibitor, was 30 times more effective as a competitor of [ 125 I]IHYP binding in M cells than in F cells.It thus appears that, whereas M and F cells share a similar number of receptors per cell and similar affinities for [ 125 I]IHYP, the receptors in the two cell types nevertheless can be distinguished on the basis of their subclassification.These results also emphasize the importance of obtaining a homogeneous cell population for studies of the /{-adrenergic receptor in cultured cardiac tissue.Circ Res 47: 41-48, 1980/2-ADRENERGIC receptors with high affinity, low capacity, and stereoselectivity have been identified in cardiac microsomal preparations.Some (U' Prichard et al., 1978), but not all (Harden et al, 1976;Alexander et al., 1975), of these analyses have supported physiological observations that the heart can be subclassified as a /?i system (Lands et al., 1967), since epinephrine and norepinephrine are equipotent in binding to the receptor.In addition, direct binding studies have shown that there are changes in the number of yS-adrenergic receptors in certain disorders associated with altered adrenergic tone (Ciaraldi and Marinetti, 1977;Williams et al., 1977;Limas and Limas, 1978).
Metabolic control of diabetes in general practice clinics: comparison with a hospital clinic.
Authors: B M Singh, M R Holland, P A Thorn
Journal: BMJ (1984)

An assessment was made of the degree of metabolic control achieved in diabetic patients attending mini clinics run by general practitioners compared with that in matched diabetic patients attending a hospital clinic. Patients were grouped according to whether they were being treated with diet alone, an oral hypoglycaemic, insulin once daily, or insulin twice daily. Statistical analysis showed no significant difference between patients attending mini clinics and those attending the hospital clinic in retrospective mean blood glucose, retrospective mean glycosylated haemoglobin (HbA1), or prospective HbA1 concentrations. General practitioners providing diabetic care on an organised basis can achieve a degree of glycaemic control in diabetic patients equal to that reached by a hospital clinic.
Abstract 4896: The detection and analysis of epigenetic and genetic changes in ovarian tumor tissue
Authors: Matthew Poulin, Jessica Xu, Liying Yan
Journal: Cancer Research (2010)

Abstract Human ovarian cancer is the fifth leading cause of cancer-related deaths. Most ovarian cancers are ovarian epithelial carcinomas or malignant germ cell tumors. Similar to other cancers, the early diagnosis of ovarian cancer is critical for treatment of the disease and the better chance for recovery. If diagnosed and treated early when the cancer is confined to the ovary, the 5-year survival rate is over 90%. Many studies involving various types of human cancers proved and aberrant miRNA expression occurs in many cancers, even at the early stage of the diseases, indicating its causative role. We have analyzed 10 ovarian tumors and their associated normal tissue, and two ovarian cancer cell lines, with methylation assays for over 25 different cancer related genes (p16, ESR, BRCA1, Rassf1, RAR beta, ECAD, etc.) including several miRNA genes. Global methylation assays show the ovarian tumors to be hypomethylated compared to the corresponding normal tissue. Several of the miRNA genes we have analyzed in ovarian tumor tissue show statistically changes in methylation pattern within their promoters compared with adjacent normal tissue. ANOVA analysis shows a variance with a p value of 0.00001. Expression analysis will be performed to correlate with the methylation data. Additionally, an extensive SNP analysis will be conducted on these tissues in order to establish specific screening parameters that will aid in early detection of this disease. 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 4896.
Potassium Perchlorate in Thyrotoxicosis
Authors: A. W. G. Goolden, J. R. Mallard
Journal: BMJ (1960)

Abstract  SNP heritability of a trait is measured by the proportion of total variance explained by the additive effects of genome-wide single nucleotide polymorphisms (SNPs). Linear mixed models are routinely used to estimate SNP heritability for many complex traits. The basic concept behind this approach is to model genetic contribution as a random effect, where the variance of this genetic contribution attributes to the heritability of the trait. This linear mixed model approach requires estimation of ‘relatedness’ among individuals in the sample, which is usually captured by estimating a genetic relationship matrix (GRM). Heritability is estimated by the restricted maximum likelihood (REML) or method of moments (MOM) approaches, and this estimation relies heavily on the GRM computed from the genetic data on individuals. Presence of population substructure in the data could significantly impact the GRM estimation and may introduce bias in heritability estimation. The common practice of accounting for such population substructure is to adjust for the top few principal components of the GRM as covariates in the linear mixed model. Here we propose an alternative way of estimating heritability in multi-ethnic studies. Our proposed approach is a MOM estimator derived from the Haseman-Elston regression and gives an asymptotically unbiased estimate of heritability in presence of population stratification. It introduces adjustments for the population stratification in a second-order estimating equation and allows for the total phenotypic variance vary by ethnicity. We study the performance of different MOM and REML approaches in presence of population stratification through extensive simulation studies. We estimate the heritability of height, weight and other anthropometric traits in the UK Biobank cohort to investigate the impact of subtle population substructure on SNP heritability estimation.
Lead Poisoning after Ingestion of a Foreign Body Retained in the Stomach
Authors: Frederick C. Biehusen, Edwin J. Pulaski
Journal: New England Journal of Medicine (1956)

IN children it is generally accepted that conservative measures are indicated in the management of swallowed foreign bodies once they reach the stomach. If the object is small, the period of retention in the stomach is usually short, and the patient seldom has further difficulty in passing the object. Generally, these statements are valid. If the foreign body is retained in the stomach, however, each case must be managed individually, and the possibility that the object swallowed contains lead must be seriously considered.Case ReportA 23-month-old boy was admitted to Tripler Army Hospital, having been referred from elsewhere to . . .
Relationship between Coronary Stent Restenosis and Plasma Urotensin II Level
Authors: Fethi Yavuz, Orhan Özer, Süleyman Ercan, Murat Yüce, Hamdi Püşüroğlu, Mustafa Ürkmez, Vedat Davutoğlu, Hayri Alıcı, Mehmet Kaplan, Fuat Başanalan, Mehmet Tarakçıoğlu
Journal: Journal of the American College of Cardiology (2013)
Drugs exported from India to Africa are poorer quality than those sent elsewhere
Authors: O. Dyer
Journal: BMJ (2014)

Generic drugs exported from India to Africa are of lower quality than those exported to middle income countries, an investigation that compared the strengths of four common medications bought at pharmacies around the world has found.

The study, published as a working paper by the US National Bureau of Economic Research,1 measured the quantity of active ingredients found in two mainstream antibiotics, ciprofloxacin and erythromycin, and in two tuberculosis drugs, isoniazid and rifampicin. The drugs were purchased over the counter in five Indian cities, 12 African countries, and five middle income countries (Brazil, China, Russia, Thailand, and Turkey).

Of 1470 samples, the …
Abstract 1945: A novel self assembled taxane nanoparticles for breast cancer chemotherapy
Authors: Ashish A. Kulkarni, Hua Xiang Soh, Poulomi Sengupta, Sudipta Basu, Shiladitya Sengupta
Journal: Cancer Research (2012)

Abstract Breast cancer is the most frequently diagnosed form of cancer and a second leading cause of cancer deaths among women in the United States, with an estimated 207,090 new cases and 39,840 deaths since the beginning of 2010. Taxane-based chemotherapeutic agents are extensively used as a treatment for breast cancer and have shown important clinical benefits in both adjuvant and metastatic settings. However, the therapeutic efficacy of these drugs is hampered by limitations such as poor water solubility, narrow therapeutic indices and significant off-target toxicities which limit its dose escalations and treatment frequency. Also, current drug delivery strategies often suffer from constraints such as lower potency, low loading, non-biocompatibility/ non-biodegradability and uncontrolled release of the drug. Clearly, there is an urgent need for a paradigm shift in the strategies for the development of drug delivery vehicles for breast cancer management. We propose a novel approach in the design of nanomedicine where an active molecule can self-assemble into a nanoparticle resulting in increased loading, improved antitumor outcome and reduced off-target side effects. Different taxane analogs were attached to cholesterol using an acid labile linker. The self assembly of taxane-cholesterol conjugate was facilitated by phosphatidylcholine and DSPE-PEG to form well defined nano-sized particles. The loading of 10-15 μg/μL of drugs was obtained and sustained release of drugs was observed at pH 5.5 over 48h. In a preliminary cell viability studies, the taxane nanoparticles showed comparable efficacy to drug alone. Next, in order to achieve tumor specific homing of the nanoparticles, we plan to incorporate multiple copies of iRGD peptide on the nanoparticle surface that will bind to αvβ3 integrins overexpressed on the endothelium of tumor vessels and help in effective internalization of nanoparticles. The optimum density of peptides on the nanoparticle surface will be achieved by conjugating the peptide to DSPE-PEG. We believe that this study will not only uncover a novel and most effective nanotechnology-based approach for breast cancer treatment but will also eventually lead to an improvement in the quality of life of patients at minimum cost. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1945. doi:1538-7445.AM2012-1945
Staphylococcal sepsis in a new surgical ward.
Authors: P. M. Rountree, M. A. Beard, J. Loewenthal, J. May, S. B. Renwick
Journal: BMJ (1967)

Thyrotoxicosis-Smith and Wilson result of '3II unless they had been off the drugs for at least six months.The initial control of hyperthyroidism by 13'I alone was slower in the half-dose group.After three years the results were similar, two-thirds being euthyroid in each group.There- after they were better in the half-dose group.There was one recurrence of thyrotoxicosis in the conventional-dose group and one in the half-dose group.The incidence of hypothyroidism rose steadily in the con- ventional-dose group from 80/, after one year to 29% after five years.In the half-dose group it was reduced to 4% and 70,% at the corresponding intervals.The advantages of treating thyrotoxicosis with a small dose of 13ll, followed when necessary by antithyroid drug therapy, are discussed.Further trials are required to determine the.optimal dose of 131I.We are grateful to the Endowment Fund of the United Sheffield Hospitals for financial support and to Miss Sandra Taylor for valuable technical assistance.We should like to thank our many colleagues in the department who over the
Disseminated Trichosporon beigelii (cutaneum) Infection in an Artificial Heart Recipient
Authors: Katherine A. Murray-Leisure, Robert C. Aber, Lawrence J. Rowley, Peter C. Applebaum, Craig B. Wisman, John L. Pennock, William S. Pierce
Journal: JAMA (1986)

A 44-year-old man with end-stage ischemic cardiomyopathy was supported with an intra-aortic balloon and The Penn State Heart (artificial) prior to orthotopic cardiac transplantation on the 14th hospital day. At the time of transplantation, intraoperative cultures of pericardial and mediastinal fluid showed growth of<i>Trichosporon beigelii</i>(<i>cutaneum</i>). Shortly thereafter the patient developed visceral dissemination of<i>T beigelii</i>with no associated skin lesions. He was treated with amphotericin B and rifampin, but postmortem examination showed persistent, disseminated infection. (<i>JAMA</i>1986;256:2995-2998)
Clinical Features of Schizophrenia and Linkage to Chromosomes 5q, 6p, 8p, and 10p in the Irish Study of High-Density Schizophrenia Families
Authors: Kenneth S. Kendler, John M. Myers, F. Anthony O’Neill, Rory Martin, Bernadette Murphy, Charles J. MacLean, Dermot Walsh, Richard E. Straub
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Schizophrenia is clinically heterogeneous. Recent linkage studies suggest that multiple genes are important in the etiology of schizophrenia. The authors examined the hypothesis of whether the clinical variability in schizophrenia is due to genetic heterogeneity. METHOD: Using data from the Irish Study of High-Density Schizophrenia Families (N=265 pedigrees; N=1,408 individuals), the authors attempted to predict, from major symptoms and signs of psychosis, evidence for linkage within families for schizophrenia-related disorders to chromosomal regions 5q21–5q31, 6p24–6p22, 8p22–8p21, and 10p15–10p11. RESULTS: No substantial evidence was found for associations between clinical features of schizophrenia and linkage to chromosomes 5q, 6p, or 10p. However, affected individuals from families with evidence for linkage to 8p had significantly more affective deterioration, poorer outcome, more thought disorder, and fewer depressive symptoms than affected individuals from the other families in the study. CONCLUSIONS: These results raise the possibility that the putative susceptibility gene for schizophrenia localized in the 8p22–8p21 region may predispose individuals to the core dementia-praecox syndrome described by Kraepelin more than 100 years ago.
Five cases of alpha chain disease
Authors: W. F. Doe, K. Henry, J. R. Hobbs, F. A. Jones, C. E. Dent, C. C. Booth
Journal: Gut (1972)

Five patients suffering from alpha chain disease are described. Clinically the patients presented with clubbing and the symptoms of malabsorption. There was a characteristic, predominantly plasma cell infiltrate of the wall of the small intestine. Spread of the plasmacytosis beyond the small intestine to bone marrow (1), peripheral blood (1), and probably the nasopharyngeal lymphoid tissue (1) is described. Fragments of the heavy chain of IgA (alpha chain) were found in serum (5), urine (3), jejunal fluid (2), and saliva (1). The jejunal biopsy of one patient was shown to synthesize free alpha chain in tissue culture. A new and simple immunoselection technique for the identification of free alpha chain is described. Marked clinical remissions were achieved in two patients treated with intermittent cytotoxic and steroid therapy, and in a third patient who received intermittent cytotoxic therapy and tetracycline.
Abstract P5-11-02: The Carry-Over Effect of Adjuvant Zoledronic Acid: Comparison of 48- and 62-Month Analyses of ABCSG-12 Suggests That the Benefits of Combining Zoledronic Acid with Adjuvant Endocrine Therapy Persist Long after Completion of Therapy
Authors: M Gnant, B Mlineritsch, H Stoeger, G Luschin-Ebengreuth, D Heck, G Steger, R Jakesz, C Singer, H Eidtmann, R. Greil
Journal: Cancer Research (2010)

Abstract Background: ABCSG-12 examined the efficacy of ovarian suppression using goserelin combined with tamoxifen (TAM) or anastrozole (ANA) ± zoledronic acid (ZOL) in premenopausal patients with endocrine-responsive early breast cancer. Results at 48 months and at 62 months show that adding ZOL significantly improved disease-free survival (DFS) and reduced disease recurrence. Methods: Premenopausal patients with endocrine-responsive early breast cancer (N = 1,803) were randomized to goserelin (3.6 mg q28d) and TAM (20 mg/d) or ANA (1 mg/d) ± ZOL (4 mg q6mo) for 3 years. Endpoints included DFS and overall survival, both analyzed using log-rank test and Cox models. Results: At 48 months’ median follow-up, ZOL significantly reduced the risk of DFS events by 36% versus no-ZOL (hazard ratio [HR] = 0.64; P = .01); this was maintained at 62 months’ follow-up (HR = 0.68; P = .009). In addition, the trend toward reduced risk of death with ZOL was maintained at both 48 months (HR = 0.60; P = .11) and 62 months (HR = 0.66; P = .10) compared with no-ZOL. Patients receiving ZOL also had fewer distant recurrences compared with no-ZOL: 29 versus 41 events at 48 months, and 44 versus 56 events at 62 months. No significant renal adverse events or confirmed cases of osteonecrosis of the jaw (ONJ) have been reported. Conclusions: Comparisons of 48- and 62-month data suggest a possible carry-over of the ZOL anticancer benefit 2 years after treatment completion. Additional analyses will be presented, including disease outcomes during therapy and after treatment, as well as overall survival analyses. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-02.
Receipt of maintenance therapy is most predictive of survival in older acute lymphoblastic leukemia patients treated with intensive induction chemotherapy regimens
Authors: Daniel J. Landsburg, Edward Stadtmauer, Alison Loren, Steven Goldstein, Noelle Frey, Sunita D. Nasta, David L. Porter, Donald E. Tsai, Alexander E. Perl, Elizabeth O. Hexner, Selina Luger
Journal: American Journal of Hematology (2013)

While the prognosis for older adults diagnosed with acute lymphoblastic leukemia (ALL) is frequently poor, long-term survival can be achieved in patients treated with curative intent. We reviewed the outcomes of 37 patients age ≥60 treated at our institution with either DVP- or hyperCVAD-based chemotherapy regimens from 2003-2011. In this patient population, a complete response rate of 92%, relapse rate of 56% and median overall survival of 18.1 months was experienced. Univariate analysis revealed that receipt of maintenance therapy vs. no maintenance therapy was associated with a statistically-significant impact on overall survival (p = 0.001, HR 0.15 for death), while disease-related characteristics including high-risk white blood cell count at diagnosis and Philadelphia chromosome status as well as treatment-related factors including chemotherapy regimen or completion of intensive therapy were not. Many patients were unable to initiate or remain on maintenance therapy due to toxicities including infections and cytopenias. Our analysis reveals the benefit of prolonged therapy in the treatment of older adults with ALL as well as the high incidence of treatment-related toxicity experienced by these patients.
Physicians must not be misled by arguments against screening with densitometry
Authors: R. B Mazess
Journal: BMJ (1996)

EDITOR,—As the person chiefly responsible for the development of bone densitometry, I wish to reply to the unreasonable arguments of Trevor A Sheldon and colleagues that the reply by David Barlow and colleagues does not address.1 Critics mistakenly dispute the use of densitometry for assessing risk by questioning its sensitivity in diagnosing fracture. Using densitometry to diagnose a fracture is comparable to diagnostic use of blood pressure for stroke or lipid concentrations for infarction. Bone density indicates the risk, not the presence of a …
Immunoglobulin G4‐related sclerosing cholangitis
Authors: Deepak Joshi, George J. Webster
Journal: Hepatology (2014)

1Department of GastroenterologyUniversity College London HospitalLondonUnited Kingdom *Address reprint requests to: George J. Webster, M.D., F.R.C.P., Department of Gastroenterology, University College Hospital, Ground Floor West, 250 Euston Road, London, NW1 2PG, UK. E‐mail: [email protected]; fax: +020 3447 9217.
Remnant Lipoproteins Induce Proatherothrombogenic Molecules in Endothelial Cells Through a Redox-Sensitive Mechanism
Authors: Hideki Doi, Kiyotaka Kugiyama, Hideki Oka, Seigo Sugiyama, Nobuhiko Ogata, Shun-ichi Koide, Shin-ichi Nakamura, Hirofumi Yasue
Journal: Circulation (2000)

Background —Triglyceride-rich lipoproteins (TGLs) are atherogenic. However, their cellular mechanisms remain largely unexplained. This study examined the effects of isolated remnant-like lipoprotein particles (RLPs) on the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and tissue factor (TF), proatherothrombogenic molecules, in cultured human endothelial cells. Methods and Results —RLPs were isolated from plasma of hypertriglyceridemic patients by use of the immunoaffinity gel mixture of anti–apoA-1 and anti–apoB-100 monoclonal antibodies. The incubation of cells with RLPs significantly upregulated mRNA and protein expression of these molecules. Total TGLs ( d &lt;1.006) and LDL had fewer or minimal effects on expression of these molecules compared with RLPs. RLPs increased intracellular oxidant levels, as assessed with an oxidant-sensitive probe. Combined incubation with α-tocopherol or N -acetylcysteine, both antioxidants, suppressed RLP-induced increase in expression of these molecules. In patients with higher plasma levels of RLPs, plasma levels of soluble forms of ICAM-1 and VCAM-1 were significantly higher than in patients with lower RLP levels. Treatment with α-tocopherol for 1 month decreased levels of the soluble adhesion molecules concomitantly with an increase in resistance of RLPs to oxidative modification in patients with high RLP levels. Conclusions —RLPs upregulated endothelial expression of ICAM-1, VCAM-1, and TF, proatherothrombogenic molecules, partly through a redox-sensitive mechanism. RLPs may have an important role in atherothrombotic complications in hypertriglyceridemic patients.