tbuckley/cabot-search huggingface dataset:
Increased hepatic arterial blood flow in acute viral hepatitis: Assessment by color doppler sonography
Authors: Katsuaki Tanaka, Konomi Mitsui, Manabu Morimoto, Kazushi Numata, Shuji Inoue, Yutaro Takamur, Makoto Masumura
Journal: Hepatology (1993)

To evaluate the effect of acute viral hepatitis on hepatic arterial blood flow, we performed color Doppler sonography with point-spectral analysis in 15 patients with acute viral hepatitis and compared the results with those in 15 normal volunteers. During the acute phase of hepatitis, the peak-systolic and enddiastolic velocity of the hepatic artery were significantly larger than those in normal arteries (p &lt;0.01). During the recovery phase, these indexes of the hepatic artery decreased significantly to the control levels (p &lt;0.01). The resistive indexes related to vascular resistance in the hepatic artery during the acute phase were significantly less than those in normal arteries (p &lt;0.01), and they increased significantly to the control levels during the recovery phase (p &lt;0.01). No significant correlation was found between these indexes of the hepatic artery and conventional liver function parameters. However, the interval between the acute phase and the recovery phase did correlate negatively with the peak-systolic velocity of the hepatic artery in the acute phase (r = −0.630, p &lt;0.05) and with the end-diastolic velocity (r = −0.514, p &lt; 0.05). We conclude that color Doppler sonography is useful for imaging increased hepatic arterial blood flow in patients with acute viral hepatitis. We believe that increased hepatic arterial blood flow during the acute phase may provide a marker for earlier recovery from hepatitis-induced damage. (Hepatology 1993;18:21-27).
Abstract B26: Design and synthesis of furoquinoline derivatives as potential drug candidates for the treatment of lung cancers.
Authors: Cherng-Chyi Tzeng, Chih-Hua Tseng, Yeh-Long Chen
Journal: Clinical Cancer Research (2014)

Abstract Quinoline moiety is present in many classes of biologically active compounds. Recently, we have synthesized certain quinolone, 2-phenylquinoline, 2-furanylquinoline, and 4-anilinofuro[2,3-b]quinoline derivatives for biological evaluations. Among them, 1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone (CIL-102) was the most potent with a mean GI50 value of 0.025 μM against the growth of nine types of cancer cells and therefore, was further evaluated on its effects of cell cycle distribution. Results indicated CIL-102 induces cell cycle arrest in G2/M followed by apoptosis. CIL-102 bounds to tubulin at a single site with a dissociation constant of 0.4 μM. An analysis of the modified Dixon plot suggested that CIL-102 competitively inhibited the binding of podophyllotoxin, a colchicine-binding site agent, to tubulin. However, some drawbacks such as lack of selective cytotoxicity, poor oral bioavailability, and poor water solubility exhibited by CIL-102 prompted us to search for newer derivatives. Through extensive structural optimization, the new lead compound named as CYW-1865 which possesses aminoalkoxyimino side chain, exhibited selective anticancer activity, higher oral bioavailability, and higher water solubility than that of CIL-102. Xenographic studies indicated the tumor size with CYW-1865 treated nude mice was significantly lower than control. Further evaluation in an orthotopic lung cancer model indicated that CYW-1865 can be absorbed readily through oral administration, distributed to lung tissue, and exhibited significant efficacy in inhibiting the growth of lung cancers. Strategies for design and synthesis of CYW-1865 and its further structural optimization will be presented. Citation Format: Cherng-Chyi Tzeng, Chih-Hua Tseng, Yeh-Long Chen. Design and synthesis of furoquinoline derivatives as potential drug candidates for the treatment of lung cancers. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B26.
Maintenance Amphotericin B for Cryptococcal Meningitis in the Acquired Immunodeficiency Syndrome (AIDS)
Authors: Abigail Zuger
Journal: Annals of Internal Medicine (1988)

We previously reported our experience (1) with the treatment of cryptococcal infections in patients with the acquired immunodeficiency syndrome (AIDS). Like other investigators (2, 3) we noted a high relapse rate and a poor response to treatment among patients with relapsed infections. Continued weekly infusions of amphotericin B after a standard course of therapy seemed to offer our patients some protection against relapse. Of seven patients who received maintenance therapy with amphotericin B, none had relapses; four of eight patients had relapses when maintenance therapy was not administered. This observation prompted us to recommend maintenance amphotericin B for all patients
Abstract 1798: Identification of pan-Trk inhibitors for the treatment of Trk-driven cancers
Authors: Karyn S. Bouhana, Anna M. Gomez, Taylor J. Alford, Richard Woessner, Ira von Carlowitz, Patrice A. Lee, Steven D. Andrews, Shannon L. Winski
Journal: Cancer Research (2012)

Abstract The Trk family of genes, which includes trkA/NTRK1, trkB/NTRK2 and trkC/NTRK3, encode the tyrosine kinase receptors for the neurotrophin family of nerve growth factors. Deregulated kinase activity of trk family members is associated with human cancer. Oncogenic translocations involving trkC kinase domain have been identified in AML, salivary gland carcinoma, adult secretory breast cancer, congenital fibrosarcoma, and pediatric nephroma. Oncogenic trkA translocations have been reported in papillary thyroid and colorectal cancers. We have identified orally bioavailable, potent and selective ATP-competitive inhibitors of the trk family of receptor tyrosine kinases and are developing these for the treatment of Trk-driven cancers. AR523 is a pan-Trk inhibitor which demonstrates similar activity against TrkA, TrkB and TrkC receptors in a cell based assay (IC50 ∼10 nM). In a screen at 1 µM against a panel of 230 kinases, AR523 inhibited only three additional kinases more than 50% (TNK2, Bmx and Txk). In cell culture AR523 was found to exhibit selective anti-proliferative activity toward the cell line KM12, which harbors the oncogenic TPM-TrkA translocation, while exhibiting no activity toward HT29, a cell line with no trk gene rearrangements. Studies in mice engrafted with KM12 tumors revealed significant anti-tumor and pharmacodynamic activity of AR523. Administration of a single oral dose of AR523 reduced tyrosine phosphorylation of TrkA by nearly 80% at twelve hours after dosing. Parallel analysis of Akt and Erk revealed reduced phosphorylation of these downstream effectors. Administration of 100 mg AR523 daily for two weeks to mice with KM12 xenografts produced mean tumor growth inhibition of 86% and a mean of 42% tumor regression. AR523 exhibits dose dependent inhibition of tumor growth at 10 and 30 mg/kg in KM12 xenografts with 54 and 72% TGI respectively. AR523 was well-tolerated, causing no weight loss or deaths compared with vehicle control. Increasingly Trk mutations have been shown to be activating and the use of Trk inhibitors may provide a new therapeutic strategy for targeted treatment. 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 1798. doi:1538-7445.AM2012-1798
The level of Hb F‐sardinia (α<sub>2</sub><sup>A</sup> γ<sub>2</sub><sup>75IIe→Thr</sup>) in the fetal hemoglobin of sardinian β‐thalassemic homozygotes determined by isoelectric focusing
Authors: B. Masala, L. Manca, M. Formato, A. Matera
Journal: American Journal of Hematology (1986)

Abstract A simple thin‐layer isoelectric focusing technique was used to separate Hb F‐Sardinia, containing the A γ T ‐globin chain, from the Hb F containing the γ‐ and the A γ I ‐ globin chains. The identity of the slow‐moving Hb F fraction as Hb F‐Sardinia was verified by PAGE. A negative correlation (R 2 = 0.747, p &lt; 0.001) was found between the percent Hb F‐Sardinia and percent G γ‐chain in homozygotes for β‐thalassemia. Of 31 Sardinian β‐thalassemic patients studied, 21 were homozygous and eight heterozygous for the A γ T polymorphism with a gene frequency of 0.823. The mean values of Hb F‐Sardinia were 39.1 ± 5.9% for the homozygotes and 17.1 ± 3.6% for the heterozygotes. The percentage of Hb F‐Sardinia found in β°‐thalassemic newborns was similar to that of corresponding normal newborns who also had the A γ T poly‐morphism. No measurable differences in the percent Hb F‐Sardinia level were observed among β°‐thal patients who were polytransfused, β°‐thal patients studied before transfusion, and β°‐thal patients exhibiting the intermediate form of the disease who had never been transfused.
diagnosis is based on clinical features
Authors: D. Burgner
Journal: BMJ (2003)

Kawasaki disease is a not uncommon and probably underdiagnosed paediatric vasculitis. The incidence of the disease in the United Kingdom, as in other countries, seems to be increasing.1 Kawasaki disease often enters the differential of febrile childhoodillnesses, and this case shows the difficulties of making a timely diagnosis. Early recognition iscritical; Kawasaki disease is the commonest cause of acquired heart disease in children, with about one third of untreated children developing coronary artery damage with a short term increased risk of death and serious long term sequelae. Prompt treatment within the first 10 days prevents overt coronary damage in most cases.2 …
Tuberculosis: Incidence among American Medical Students, Prevention and Control and the Use of BCG
Authors: William A. Abruzzi, Rufus J. Hummel
Journal: New England Journal of Medicine (1953)

WITH the help of the Association of American Medical Colleges, a survey letter was prepared and sent to 71 four-year, Class "A" medical schools. This letter inquired into the incidence of tuberculosis among the medical students between 1940 and 1950, and the tuberculin testing, chest x-ray examinations and over-all prevention and control programs employed in those years. Data were received from 63 institutions — in unusable form from 1; no data were available from 1 school; they are still forthcoming from 2 others; and no answers were ever received from 5 institutions.In addition, information on incidence, control and prevention . . .
Should Insurance Coverage for in Vitro Fertilization Be Mandated?
Authors: David S. Guzick
Journal: New England Journal of Medicine (2002)

Not long ago, in vitro fertilization was the stuff of science fiction.1 Even after the birth of the first baby from in vitro fertilization in 1978, such births were initially few and far between, and there was skepticism about the future of in vitro fertilization as a mainstream medical procedure. Insurance companies considered it experimental and therefore not eligible for coverage in benefit plans. Twenty years later, data collected by the Centers for Disease Control and Prevention from in vitro fertilization clinics in the United States2 indicated that more than 58,000 in vitro fertilization cycles were performed annually, resulting in . . .
706. DNA Vaccine Strategy Against Chronic B-Cell Lymphoma: Anti-Idiotypic CDR3 Vaccination
Authors: Monica Rinaldi, Daniela Fioretti, Sandra Iurescia, Emanuela Signori, Pasquale Pierimarchi, Giancarlo Tonon, Vito Michele Fazio
Journal: Molecular Therapy (2005)

B-cell lymphomas express tumor-specific immunoglobulin, the variable regions of which (Id determinants) are tumor-specific antigens and therefore are suitable targets for vaccine immunotherapy. Promising results have been obtained in clinical studies of Id vaccination using Id proteins or naked DNA Id vaccines. Several reports have indicated that the immunodominant epitopes of the clone-specific Ig lie within the hypervariable CDR3 regions. Our group has previously tested the possibility of using the short peptide encompassing the CDR3 of immunoglobulin heavy chain (VH-CDR3) as a target for eliciting a tumor specific immune response via DNA-based vaccination. We demonstrated that DNA immunization of outbred mice with different patient-derived VH-CDR3 peptides elicited antibodies able to recognize native antigens on individual patient's tumor cells. These findings prompted us to investigate the immune response and tumor protection following CDR3-based DNA vaccination in the 38C13 B lymphoma as tumor model.
APICAL HYPOKINESIS IS A SENSITIVE MARKER OF EARLY RIGHT VENTRICULAR DYSFUNCTION IN PULMONARY HYPERTENSION.
Authors: Leticia A. Fernandez-Friera, Ana Garcia-Alvarez, Ajith Nair, Gabriela Guzman, Alaitz Romero, Juan Gaztanaga, Valentin Fuster, Mario Garcia, Javier Sanz
Journal: Journal of the American College of Cardiology (2010)
HSV-mediated Transfer of Artemin Overcomes Myelin Inhibition to Improve Outcome After Spinal Cord Injury
Authors: Zhigang Zhou, Xiangmin Peng, David J Fink, Marina Mata
Journal: Molecular Therapy (2009)

Artemin is a neurotrophic factor of the glial cell line–derived neurotrophic factor (GDNF) family of ligands that acts through the GDNF family receptor α3 (GFRα3)/ret receptor found predominantly on sensory and sympathetic neurons. In order to explore the potential utility of artemin to improve functional outcome after spinal cord injury (SCI), we constructed a nonreplicating herpes simplex virus (HSV)-based vector to express artemin (QHArt). We found that QHArt efficiently transfects spinal cord neurons to produce artemin. Transgene-mediated artemin supported the extension of neurites by primary dorsal root ganglion neurons in culture, and allowed those cells to overcome myelin inhibition of neurite extension through activation of protein kinase A (PKA) to phosphorylate cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and increase expression of arginase I. Intraspinal injection of QHArt immediately after thoracic spinal cord dorsal over hemisection produced a statistically significant improvement in motor recovery over the course of four weeks measured by locomotor rating score. Artemin is a neurotrophic factor of the glial cell line–derived neurotrophic factor (GDNF) family of ligands that acts through the GDNF family receptor α3 (GFRα3)/ret receptor found predominantly on sensory and sympathetic neurons. In order to explore the potential utility of artemin to improve functional outcome after spinal cord injury (SCI), we constructed a nonreplicating herpes simplex virus (HSV)-based vector to express artemin (QHArt). We found that QHArt efficiently transfects spinal cord neurons to produce artemin. Transgene-mediated artemin supported the extension of neurites by primary dorsal root ganglion neurons in culture, and allowed those cells to overcome myelin inhibition of neurite extension through activation of protein kinase A (PKA) to phosphorylate cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and increase expression of arginase I. Intraspinal injection of QHArt immediately after thoracic spinal cord dorsal over hemisection produced a statistically significant improvement in motor recovery over the course of four weeks measured by locomotor rating score.
Half a billion here, half a billion there
Authors: T. Delamothe
Journal: BMJ (2010)

To improve access for patients to costly medicines the Department of Health is looking at joint payment schemes with drug companies (doi:10.1136/bmj.c2832). This week we publish an object lesson in how not to run one.

As James Raftery explains, the UK’s first risk sharing scheme began in 2002 as a ruse to get round NICE’s ruling against use of interferon beta and glatiramer acetate in multiple sclerosis (doi:10.1136/bmj.c1672). The NHS would pay for the drugs, but cost effectiveness would be closely monitored, with an agreement to reduce prices if patients’ outcomes were worse than predicted. However, although outcomes were much worse than predicted ( BMJ 2009;339:b4677, doi:10.1136/bmj.b4677), the prices haven’t come down.

The …
Inconsistencies in Coding of Race and Ethnicity Between Birth and Death in US Infants
Authors: Robert A. Hahn
Journal: JAMA (1992)

To ascertain the consistency of the racial and ethnic classification of US infants between birth and death and its impact on infant mortality rates.All US infants born from 1983 through 1985 who died within a year.We used the national linked birth/infant-death computer tape, augmented with information on infants' race and ethnicity at death, to compare the coding of race and Hispanic ethnicity at birth and at death. We also assessed infant mortality rates by race and ethnicity as defined (1) by the standard algorithm and (2) by the rule that, beginning in published tabulations for 1989, assigns newborns the race of their mothers. Finally, we estimated infant mortality rates based on consistent coding of race and ethnicity at birth and death.Inconsistency in the coding of race is low for whites (1.2%), greater for blacks (4.3%), and greatest for races other than white or black (43.2%). Most infants reclassified at death (87.3%) are classified as white at death. Inconsistency in coding is lower for non-Hispanic whites (3.5%) and non-Hispanic blacks (3.3%) than for Hispanic populations (30.3%). Compared with the standard algorithm for calculation of infant mortality, consistent definition at birth and death produces rates 2.1% lower for whites, and higher for all other groups--3.2% for blacks, 46.9% for American Indians, 33.3% for Chinese, 48.8% for Japanese, 78.7% for Filipinos, and 8.9% for Hispanics.The coding of race and ethnicity of infants at birth and death is remarkably inconsistent, with substantial impact on the estimation of infant mortality rates. A need exists to reconsider the nature and definition of race and ethnicity in public health.
Apolipoprotein E and Progression of Chronic Kidney Disease
Authors: Charles C. Hsu, W. H. Linda Kao, Josef Coresh, James S. Pankow, Jane Marsh-Manzi, Eric Boerwinkle, Molly S. Bray
Journal: JAMA (2005)

Apolipoprotein E (APOE) genetic variation has been implicated in diabetic nephropathy with the epsilon2 allele increasing and the epsilon4 allele decreasing risk. APOE allelic associations with chronic kidney disease beyond diabetic nephropathy are unknown, with no studies reported in high-risk African American populations.
Histone 3.3 Participates in a Self-Sustaining Cascade of Apoptosis That Contributes to the Progression of Chronic Obstructive Pulmonary Disease
Authors: Carlos A. Barrero, Oscar Perez-Leal, Mark Aksoy, Camilo Moncada, Rong Ji, Yolanda Lopez, Karthik Mallilankaraman, Muniswamy Madesh, Gerard J. Criner, Steven G. Kelsen, Salim Merali
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Shifts in the gene expression of nuclear protein in chronic obstructive pulmonary disease (COPD), a progressive disease that is characterized by extensive lung inflammation and apoptosis, are common; however, the extent of the elevation of the core histones, which are the major components of nuclear proteins and their consequences in COPD, has not been characterized, which is important because extracellular histones are cytotoxic to endothelial and airway epithelial cells.To investigate the role of extracellular histones in COPD disease progression.We analyzed the nuclear lung proteomes of ex-smokers with and without the disease. Further studies on the consequences of H3.3 were also performed.A striking finding was a COPD-specific eightfold increase of hyperacetylated histone H3.3. The hyperacetylation renders H3.3 resistant to proteasomal degradation despite ubiquitination; when combined with the reduction in proteasome activity that is known for COPD, this resistance helps account for the increased levels of H3.3. Using anti-H3 antibodies, we found H3.3 in the airway lumen, alveolar fluid, and plasma of COPD samples. H3.3 was cytotoxic to lung structural cells via a mechanism that involves the perturbation of Ca(2+) homeostasis and mitochondrial toxicity. We used the primary human airway epithelial cells and found that the antibodies to either the C or N terminus of H3 could partially reverse H3.3 toxicity.Our data indicate that there is an uncontrolled positive feedback loop in which the damaged cells release acetylated H3.3, which causes more damage, adds H3.3 release, and contributes toward the disease progression.
Examples of uses of databases for quantitative and qualitative correlation studies between genotoxicity and carcinogenicity.
Authors: S Parodi, D Malacarne, M Taningher
Journal: Environmental Health Perspectives (1991)

In this paper we give some examples of using databases of genotoxicity and carcinogenicity for quantitative and qualitative correlation studies between short-term tests and carcinogenicity. The quality of the databases is obviously important, but one of the major deficiencies of present databases is that they are too small. Using relatively small, different databases, different results can be obtained. With small databases it is difficult to disaggregate data for homogeneous chemical classes or other types of subsets. Using the databases of Gold (carcinogenicity) and Würgler (genotoxicity), we have investigated the carcinogenic potency of genotoxic and nongenotoxic carcinogens for different chemical classes.
Outbreak of Adenovirus Infection in the Portsmouth Naval Command, 1958
Authors: P. K. Fraser, L. A. Hatch
Journal: BMJ (1959)

The Commission on Acute Respiratory Diseases of the United States Army (1946) postulated the existence of a special disease of the upper respiratory tract affecting chiefly young recruits during their first four weeks of military training.A virus agent was eventually isolated by Hilleman and Werner (1954) from cases of atypical pneumonia and acute respiratory disease, and found to be similar to a " masked " virus recovered from adenoid tissue removed at operation from young children (Rowe et al., 1953).Adenovirus infection in military recruits causes febrile upper respiratory catarrh with sore throat and cough.About half the patients develop an exudate on the tonsils, and up to 16% may show radiological evidence of pneumonitis (Hilleman, 1956).These infections are of great importance to American Service authorities, and their cost has been estimated at nine million dollars a year.Outbreaks in this country have been reported from Army and R.A.F.establishments (Tyrrell et al., 1956;Andrews et al., 1956) and from residential schools (Kendall et al., 1957).The virus has at least seventeen serotypes (Rowe et al., 1958), and to avoid confusion the term " adenovirus " was proposed to cover the group.Types 3, 4, and 7 are responsible for most military cases (Hilleman, 1956); types 1, 2, and 5 cause respiratory infections in young children; and types 6, 8, and 10 are mainly implicated in eye infections (J.Amer.Med.Ass., 1957).The outbreak reported here became manifest in the Portsmouth Naval Command in February, 1958.It was soon realized that this outbreak was larger than any previously reported from Service sources in this country, and it was decided to investigate its effect on the personnel in five of the larger establishments ( A, B, C, D, andE). Laboratory MethodsPaired sera were taken in the first ten days of illness and two weeks or more later.They were taken routinely from patients admitted to hospital with upper respiratory infections from January and from patients in sick quarters in centres A, B, and C from February until April.Convalescent sera, taken after the first ten days of illness, were obtained from patients in centres A, B, C, D, and E. They were frozen until tested by complement-fixation against antigens of influenza A, B, and C, Rickettsia burneti, adenovirus, and the psittacosis-L.G.V. group of viruses described by Andrews et al. (1956).