tbuckley/cabot-search huggingface dataset:
Why We Need a Program for the Control of<i>Chlamydia trachomatis</i>
Authors: Julius Schachter
Journal: New England Journal of Medicine (1989)

Gonococcal ophthalmia neonatorum is a potentially blinding disease. As noted elsewhere in this issue of the Journal, the introduction of silver nitrate eye drops for prophylaxis against gonococcal ophthalmia neonatorum was a major triumph of preventive medicine.1 Because we can now diagnose and treat gonococcal infections, it has been suggested that routine ocular prophylaxis should be discontinued and prevention should be based on prenatal screening and treatment of infected pregnant women. Unfortunately, Neisseria gonorrhoeae is still epidemic in this country, with an estimated 2 million infections occurring each year. The population groups at high risk for gonococcal infection often . . .
Role of Endogenous Endothelin in the Development of Graft Arteriosclerosis in Rat Cardiac Allografts
Authors: Kenji Okada, Yasuhiro Nishida, Hiroshi Murakami, Isao Sugimoto, Hiroaki Kosaka, Hironobu Morita, Chojiro Yamashita, Masayoshi Okada
Journal: Circulation (1998)

Background —The purpose of this study was to determine whether endothelin-1 (ET-1) contributes to the development of graft arteriosclerosis and whether the orally active nonpeptide endothelin receptor antagonist bosentan, which blocks both ET A and ET B receptors, can protect against this pathologic damage. Methods and Results —Recipient male Lewis rats were divided into three groups; group 1 received heterotopic heart transplantations from Lewis donors and groups 2 and 3 received transplantations from Brown-Norway donors; group 3 recipients also received bosentan orally at the dose of 20 mg/kg per day for 120 days. All recipients were given cyclosporine and were euthanized at examination 120 days after transplantation. Plasma ET-1 levels were significantly higher in group 2 than in group 1 (6.99±0.91 and 4.15±0.83 pg/mL, respectively). Strong ET-1 immunoreactivity was seen in both the thickened neointima and the media of the coronary arteries in group 2 but not in group 1. The mean ratio of the coronary luminal area to the total vascular area in group 2 (19.0±11.7%) was significantly lower than that in group 1 (34.2±9.9%) and was significantly increased in group 3 (33.2±9.2%). Conclusions —These results show that local upregulation of ET-1, mainly in the thickened neointima and the media of the coronary arteries, may play an important role in the pathogenesis of graft arteriosclerosis by stimulating ET A receptors, ET B receptors, or both. Orally active bosentan might be a useful agent for the clinical prevention of graft arteriosclerosis.
Maternal Serum AFP Screening
Authors: Aubrey Milunsky, Elliot Alpert
Journal: New England Journal of Medicine (1978)

Noninvasive diagnostic or creening technics have obvious appeal. When such approaches in pregnancy yield important information about fetal health, the vigor with which they will be pursued can easily be anticipated. This situation has been noted since the advent of maternal serum alpha-fetoprotein (AFP) testing, which made it possible to suspect a fetal neural-tube defect (NTD) with a high degree of certainty.1 , 2 NTD's (about two per 1000 births) are among the most common major congenital malformations in the United States, over 6000 affected infants being born each year. Of the approximately half who survive the first 24 hours of life, . . .
THE ULTRASTRUCTURE OF NORMAL AND PATHOLOGICAL I<scp>G</scp>M IMMUNOGLOBULINS
Authors: B. Chesebro, B. Bloth, S-E. Svehag
Journal: The Journal of Experimental Medicine (1968)

Free IgM immunoglobulins were examined in the electron microscope using the negative contrast technique. Normal human and rabbit IgM and Waldenström macroglobulins were indistinguishable from one another and revealed flexible spider-like particles with five appendages joining a central ring. The average total span of the molecules was 300 A. The appendages were about 125 x 30 A; the central ring had an outer diameter of approximately 100 A and an inner diameter of 40 A. Some purified 19S IgM preparations tended to form massive aggregates (>/=50S) which, when examined in the electron microscope, revealed enormous clumps of IgM molecules whose appendages were entangled with one another. Electron microscopy of reduced-alkylated IgM revealed total absence of intact spider-like molecules. The predominating structure observed was a round electron-dense knob about 50 A in diameter which in some cases had a fine fiber-like extension with approximate dimensions 100 x 15 A. Rabbit and human IgM molecules with antibody activity to poliovirus dried in sodium tungstosilicate on a carbon film as in preparation for electron microscopy were shown to retain nearly 100% of their poliovirus neutralizing activity after redissolving in a physiological buffer.
Diminished Prostaglandin E<sub>2</sub>Contributes to the Apoptosis Paradox in Idiopathic Pulmonary Fibrosis
Authors: Toby M. Maher, Iona C. Evans, Stephen E. Bottoms, Paul F. Mercer, Andrew J. Thorley, Andrew G. Nicholson, Geoffrey J. Laurent, Teresa D. Tetley, Rachel C. Chambers, Robin J. McAnulty
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Patients with idiopathic pulmonary fibrosis (IPF), a progressive disease with a dismal prognosis, exhibit an unexplained disparity of increased alveolar epithelial cell (AEC) apoptosis but reduced fibroblast apoptosis.Objectives: To examine whether the failure of patients with IPF to up-regulate cyclooxygenase (COX)-2, and thus the antifibrotic mediator prostaglandin (PG)E2, accounts for this imbalance.Methods: Fibroblasts and primary type II AECs were isolated from control and fibrotic human lung tissue. The effects of COX-2 inhibition and exogenous PGE2 on fibroblast and AEC sensitivity to Fas ligand (FasL)-induced apoptosis were assessed.Measurements and Main Results: IPF lung fibroblasts are resistant to FasL-induced apoptosis compared with control lung fibroblasts. Inhibition of COX-2 in control lung fibroblasts resulted in an apoptosis-resistant phenotype. Administration of PGE2 almost doubled the rate of FasL-induced apoptosis in fibrotic lung fibroblasts compared with FasL alone. Conversely, in primary fibrotic lung type II AECs, PGE2 protected against FasL-induced apoptosis. In human control and, to a greater extent, fibrotic lung fibroblasts, PGE2 inhibits the phosphorylation of Akt, suggesting that regulation of this prosurvival protein kinase is an important mechanism by which PGE2 modulates cellular apoptotic responses.Conclusions: The observation that PGE2 deficiency results in increased AEC but reduced fibroblast sensitivity to apoptosis provides a novel pathogenic insight into the mechanisms driving persistent fibroproliferation in IPF.
Potentially Important Contribution of Dextrose Used as Diluent to Hyperglycemia in Hospitalized Patients
Authors: Bryan J. Krajicek, Yogish C. Kudva, Heather A. Hurley
Journal: Diabetes Care (2005)

Several recent studies have shown increased morbidity and mortality associated with hyperglycemia in patients hospitalized for cardiovascular illnesses and acute illness requiring intensive care (1). While many of these studies have utilized intensive insulin therapy (IIT) as a means of controlling hyperglycemia, to our knowledge the possible iatrogenic contribution of intravenous medications has been overlooked.

A 78-year-old man with type 2 diabetes was hospitalized for respiratory failure. Glycemic control was suboptimal despite continuous insulin infusion. The diabetes service observed infusion of Vancomycin mixed in 250 ml of 5% dextrose (D5W) while …
Abstract 5006: High-throughput TR-FRET cellular assays for interrogating histone H3 methylation
Authors: Kun Bi, Jeanne Dudek, Spencer Hermanson
Journal: Cancer Research (2012)

Abstract Post-translational modifications such as phosphorylation, acetylation and methylation play important roles in regulating the structures and functions of histones, which in turn regulate gene expression and DNA repair and replication. Histone modifying enzymes, such as deacetylases, methyltransferases and demethylases, have been pursued as therapeutic targets for various diseases. However, detection of the activities of these enzymes in high-throughput cell-based formats has remained challenging. We have developed high-throughput LanthaScreen® cellular assays for histone H3 site-specific modifications. These assays utilize cells expressing green fluorescence protein (GFP) tagged-histone H3 transiently delivered via BacMam and terbium labeled-anti-histone H3 modification-specific antibodies. Robust time-resolved Foerster resonance energy transfer signals were detected for H3 lysine-9 di-methylation (K9me2), lysine-4 di- (K4me2) and tri-methylation (K4me3) and lysine-27 tri-methylation (K27me3). Consistent with previous reports, hypoxic stress increased K4 methylation levels and methyltransferase G9a inhibitor UNC-0638 decreased K9me2 levels significantly with little effects on other modifications. Further validation of these assays using methyltransferases-specific RNAi oligos demonstrated that EZH2-specific RNAi reduced the level of K27me3 with little effect on the other three modifications, whereas G9a RNAi and SMYD3 RNAi reduced K9me2 and K4me2/3, respectively. The use of BacMam gene delivery system enables the measurement of these histone methylations in a variety of cell backgrounds including primary cells. In conclusion, we have developed homogenous cellular assays that can enable the high-throughput screening for modulators of histone H3 methylation at various lysine sites. 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 5006. doi:1538-7445.AM2012-5006
Metabolite-based internal doses used in a risk assessment of benzene.
Authors: A J Bailer, D G Hoel
Journal: Environmental Health Perspectives (1989)

Risk assessments of benzene have been based upon both human and animal studies. In this paper, metabolite information is used to construct an internal dose (a surrogate of the biologically effective dose) for a given administered dose. The relationship between the administered dose and this internal dose is nonlinear and is well described by a Michaelis-Menten function. The administered doses from the National Toxicology Program's rodent carcinogenicity study of benzene are transformed into internal doses, and these internal doses are used in conjunction with a multistage model to compare previous estimated virtually safe doses (VSD) associated with small added health risks. The ratio of VSD for the administered dose risk assessment to the VSD from the internal dose risk assessment was approximately 1.0 for the F344/N rats and ranged from 2.5 to 5.0 for B6C3F1 mice in the National Toxicology Program study. For an occupational exposure of 1 ppm, a risk estimate of 0.7 excess cancers/1000 exposed with an upper bound of 3.5/1000 was obtained for a total metabolite internal dose risk assessment. Risk estimates based upon internal doses constructed from levels of the toxic metabolites of benzene are also presented. The implication of a dose-rate study of benzene metabolism for risk assessment is discussed, and finally, suggestions for better characterization of the dose-response function for benzene are provided.
STUDIES ON ARTIFICIAL ANTIGENS
Authors: Fred S. Kantor, Antonio Ojeda, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1963)

Dinitrophenyl conjugates of poly-L-lysine, varying in percentage conjugation and molecular weight have been found to induce skin reactivity and precipitating antibodies in guinea pigs. At best, 40 per cent of immunized animals developed delayed and immediate responses to DNP-polylysine, which is believed to reflect constitutional differences among the animals assayed. Only those animals capable of responding to DNP-polylysine, responded to an immunologically distinct poly-α-amino acid consisting of glutamyl and lysyl residues ("copolymer glu-lys"). The percentage of animals responding to the DNP-polylysine antigen decreased as the degree of DNP conjugation increased.
Siren-Equipped Probe Alerts Surgeons to Hidden Tumors
Authors: Jill Waalen
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Siren-Equipped Probe Alerts Surgeons to Hidden Tumors Get access Jill Waalen Jill Waalen Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 14, 17 July 1991, Pages 982–983, https://doi.org/10.1093/jnci/83.14.982 Published: 17 July 1991
New syndrome of hypotrichosis, striate palmoplantar keratoderma, acro-osteolysis and periodontitis not due to mutations in cathepsin C
Authors: M.A.M. Van Steensel, M. Van Geel, P.M. Steijlen
Journal: British Journal of Dermatology (2002)

We report a mother and daughter with a syndrome of hypotrichosis, striate palmoplantar keratoderma, onychogryphosis, periodontitis, acro-osteolysis and psoriasis-like skin lesions. The syndrome resembles Papillon-Lefèvre syndrome (PLS), characterized by palmoplantar keratoderma, periodontitis and psoriasis-like skin lesions, and particularly Haim-Munk syndrome, an allelic variant of PLS with acro-osteolysis. Both are caused by mutations in the cathepsin C gene (CTSC). Our patients differ in the unique nature of the palmar keratoderma and hypotrichosis. We have sequenced CTSC in the mother without finding mutations in either coding or non-coding parts of the gene. We propose that our patients suffer from a new syndrome possibly caused by mutations in a gene that has a functional or structural relation with CTSC.
Effect of beta adrenergic blockade on renin response to renal nerve stimulation.
Authors: M S Taher, L G McLain, K M McDonald, R W Schrier, L K Gilbert, G A Aisenbrey, A L McCool
Journal: Journal of Clinical Investigation (1976)

The ability of d,l-propranolol to block renin secretion in response to various extrarenal stimuli, such as hemorrhage and hypoglycemia, has been interpreted to indicate the presence of an intrarenal beta receptor regulating renin release. However, two problems complicate this interpretation: (a) the stimuli have effects outside the kidney, and (b) d,l-propranolol has a local anesthetic, as well as a beta adrenergic blocking, action. In the present study, the effects of a purely intrarenal stimulus, in the form of renal nerve stimulation (RNS), on renin secretion was examined. The effects of d,l-propranolol (anesthetic and beta-blocking activity), l-propranolol (beta-blocking activity only), and d-propranolol (local anesthetic activity only) on the renin response to RNS were examined. In a control group of animals, two sequential RNS increased mean renin secretion from 401 to 1,255 U/min (P less than 0.25) and from 220 to 2,179 U/min (P less than 0.01). In a second group the first RNS increased renin secretion from 201 to 1,181 U/min (P less than 0.01), but after d,l-propranolol was given RNS did not significantly alter renin secretion (33 to 55 U/min). In a third group the initial RNS increased renin secretion from 378 to 1,802 U/min (P less than 0.025), but after l-propranolol was given RNS had no significant effect on renin secretion (84 to 51 U/min). A fourth group of dogs showed a rise in renin secretion from 205 to 880 U/min (P less than 0.001) in response to the first RNS, while the second RNS, given after an infusion of d-propranolol, caused a rise in renin secretion from 80 to 482 (P less than 0.005). The nature of the electrical stimulus was consistent in all groups and caused no detectable changes in renal or systemic hemodynamics or in urinary electrolyte excretion. The results, therefore, indicate that renin secretion can be stimulated through intrarenal beta receptors independent of changes in systemic or renal hemodynamics or in tubular sodium reabsorption. Hence the effect of beta stimulation on renin secretion would appear to result from a direct action on the renin-secreting cells of the juxtaglomerular apparatus.
Rheumatology in the Third World.
Authors: A O Adebajo
Journal: Annals of the Rheumatic Diseases (1990)

With communicable diseases as the major medical problem in many parts of the Third World, it is pertinent to ask whether rheumatology is a relevant discipline in these countries.Should inadequate health budgets, reduced even further by crippling debt crises, be spent on research, teaching, and the provision of health services in rheumatology or is rheuma- tology simply a luxury specialty for Third World countries?My submission is that rheumatology research needs to be nurtured and encouraged in the Third World.Not only will this be of benefit to such countries but it will also contribute to the growth and advance of rheumatology world wide.
Tracheo-oesophageal fistula associated with hormonal contraception during pregnancy.
Authors: O Frost
Journal: BMJ (1976)

A case is reported of a 23-year-old primigravida who took Ovral (.5 mg DL-norgestrel and .05 mg ethinyl estradiol) for the 1st 12 weeks of pregnancy.  A hydramnios was noted subsequently and delivery was induced by syntocinon infusion.  A baby girl weighing 3000 gm was delivered who was confirmed to have an esophageal atresia with a fistula between the distal segment and the trachea.  Repair was made the same da y but the infant died 2 months later of bronchopneumonia.  Until a relation between such abnormalities and oral contraceptives has been disproven pregnancy should be definitely ruled out before oral contraceptives are prescribed.
Acute Renal Failure Following Arteriography in a Patient With Polyarteritis Nodosa
Authors: Judith S. Kaur, Jan P. Goldberg, Robert W. Schrier
Journal: JAMA (1982)

The use of radioiodinated contrast material has become an important diagnostic aid. However, certain categories of patients appear to be at risk for development of oliguric acute renal failure after receiving radiocontrast media. In the article, a patient with polyarteritis nodosa is presented who had development of oliguric azotemia after angiography; the loss in renal function was largely irreversible. The course of this patient suggests that active vasculitis, even in the presence of an inactive urine sediment, may be an additional risk factor for development of acute renal failure when considering the use of radioiodinated contrast material.
Fully human, HLA-DR-specific monoclonal antibodies efficiently induce programmed death of malignant lymphoid cells
Authors: Zoltan A. Nagy, Bernd Hubner, Corinna Löhning, Robert Rauchenberger, Silke Reiffert, Elisabeth Thomassen-Wolf, Stefan Zahn, Sigmar Leyer, Eva M. Schier, Angelika Zahradnik, Christoph Brunner, Kurt Lobenwein, Benno Rattel, Michael Stanglmaier, Michael Hallek, Mark Wing, Steve Anderson, Matt Dunn, Titus Kretzschmar, Michael Tesar
Journal: Nature Medicine (2002)
Alzheimer’s Disease: The Challenge of the Second Century
Authors: David M. Holtzman, John C. Morris, Alison M. Goate
Journal: Science Translational Medicine (2011)

In the first of our State of the Art Review series, David M. Holtzman, John C. Morris, and Alison M. Goate explore the rapid pace of Alzheimer’s disease research and the challenges to translating research breakthroughs into clinical treatments.
Familial liver and gall bladder cancer: a nationwide epidemiological study from Sweden
Authors: K Hemminki, Xinjun Li
Journal: Gut (2003)

Familial risks in liver and biliary cancers have been assessed in small case control studies, usually based on reported, but not medically verified, cancers in family members. Thus the degree of familial clustering for these cancers remains to be established.The nationwide Swedish Family-Cancer Database was used, covering 10.2 million individuals for the years 1961-1998 from the Swedish Cancer Registry. Liver and biliary tract cancers were identified from 1121 offspring between the ages of 0 and 66 years and 17 131 parents. Standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for cancers in family members.All cancers in the liver and biliary system showed a familial SIR of 1.65 (95% CI 1.05-2.46). This was mainly explained by a high risk for familial gall bladder cancer (SIR 5.21 (95% CI 2.07-10.80)) and for familial primary liver cancer with hepatocellular carcinoma histology (SIR 4.69 (95% CI 1.48-11.04)). For gall bladder and hepatocellular cancer, maternal transmission appeared to be favoured. Gall bladder cancer was associated with pancreatic cancer (SIR 2.39 (95% CI 1.23-4.18)). Primary liver cancer was associated with cervical, urinary bladder, and endocrine gland tumours. Cancer in extrahepatic bile ducts was associated with ovarian cancer and that in ampulla of Vater with thyroid cancer; however, these associations may have been fortuitous.This study has provided the first data on familial clustering of liver and gall bladder cancers, based on medically confirmed records. The risks were so high that heritable factors were likely to contribute, possibly modified by environmental factors. The demonstration of candidate genes would help to further characterise the familial risks.
Identification of Receptor Binding and Activation Sites in Endothelin-1 by Use of Site-Directed Mutagenesis
Authors: Adviye Ergul, Randall L. Tackett, David Puett
Journal: Circulation Research (1995)

Abstract This study addresses the structural requirements for the intracellular processing and receptor binding properties of endothelin-1 (ET-1). Point mutants of preproendothelin-1 cDNA, with replacement of the codons for Lys 9 of ET-1 by ones for Ala and Glu and of Ile 20 and Trp 21 by ones encoding Ala, were expressed in COS-7 cells. Competitive binding experiments on rat vascular smooth muscle cells (A-10), which were shown to be an ET A receptor–rich cell line, between [ 125 I]ET-1 and synthetic ET-1, wild-type recombinant ET-1, and recombinant [Ala 9 ]ET-1, [Glu 9 ]ET-1, [Ala 20 ]ET-1, and [Ala 21 ]ET-1 yielded K i values of 0.2±0.02, 0.2±0.02, 0.04±0.01, 1.4±0.2, 1.6±0.2, and &gt;50 nmol/L, respectively. In similar experiments with ET B receptor–rich human Girardi heart cells, the corresponding values were 0.2±0.03, 0.2±0.03, 0.2±0.04, 0.2±0.06, 1.4±0.4, and &gt;50 nmol/L. The ET A receptor–mediated contractile responses to [Glu 9 ]ET-1 and [Ala 20 ]ET-1, measured by using canine coronary artery rings, were decreased approximately fourfold to fivefold compared with the response produced by synthetic or wild-type recombinant ET-1, whereas [Ala 9 ]ET-1 was found to be more potent, and [Ala 21 ]ET-1 did not produce any contraction. These results demonstrate that Ile 20 and Trp 21 are involved in binding to both receptor subtypes. Of considerable interest was the observation that [Glu 9 ]ET-1 also blunts the ET A receptor subtype–mediated contractile response to ET-1 stimulus.
Sodium Intake and Blood Pressure in Two Polynesian Populations
Authors: I. A. M. Prior, J. Grimley Evans, H. P. B. Harvey, F. Davidson, M. Lindsey
Journal: New England Journal of Medicine (1968)

The populations of the Polynesian islands Rarotonga and Pukapuka are ethnically similar but observe different economic, social and dietary habits. In Rarotonga mean blood pressure increases with age, particularly in women. In Pukapuka rise of blood pressure with age is slight and only seen in women. Blood-pressure differences between the populations are greater than are accounted for by differences in height and weight. Dietary surveys and 48-hour urine collections from subsamples indicate that sodium intake in Rarotonga is about 50 mEq a day higher than in Pukapuka. No within-population correlation between blood pressure and 24-hour urinary sodium output is demonstrable. Many differences between the two groups may explain the differences in blood pressure, but the findings are compatible with Dahl's hypothesis that higher salt intake and higher blood pressures are related.