tbuckley/cabot-search huggingface dataset:
Hepatic preneoplasia in hepatitis B virus transgenic mice
Authors: Iljia Toshkov, Francis V. Chisari, Peter Bannasch
Journal: Hepatology (1994)

Hepatocarcinogenesis in hepatitis B virus transgenic mice was studied by means of a correlative cytomorphological and cytochemical approach at different time points in animals from 1 to 34 mo old. HBsAg–positive ground–glass hepatocytes emerged throughout the liver parenchyma in nearly all transgenic mice during the first 4 mo after birth. The panlobular expression of HBsAg persisted until foci of altered hepatocytes appeared (6 to 9 mo of age). Three different types of foci of altered hepatocytes-namely, glycogen–storage foci, mixed cell foci and glycogen–poor foci-developed. Hepatocellular adenomas and carcinomas appeared after 11 mo. Orcein staining revealed frequent transitions between ground–glass hepatocytes extensively expressing HBsAg and glycogen–storage (predominantly clear–cell) foci containing HBsAg–positive cytoplasmic components. Similar transitions between ground–glass hepatocytes and glycogenotic (clear) cells were often found in diffuse parenchymal glycogenosis at 11 or 12 mo. Remnants of HBsAg–positive material were also detected in mixed cell foci, glycogen–poor diffusely basophilic cell foci, hepatic adenoma and hepatocellular carcinoma. These findings suggest that ground–glass hepatocytes are the direct precursor of foci of altered hepatocytes and their neoplastic descendants. The extensive expression of HBsAg is gradually down–regulated during neoplastic transformation, just as the morphological the biochemical phenotypes of foci of altered hepatocytes, hepatic adenoma and hepatocellular carcinoma in transgenic mice resemble those described in chemical heterocarcinogenesis. The predominant sequence of cellular changes leading from glycogen–storage (predominantly clear cell) foci to mixed cell foci, hepatic adenoma and hepatocellular carcinoma is characterized by a gradual decrease in the activities of glycogen synthase, phosphorylase, glucose–6–phosphatase and adenylate cyclase, whereas glucose–6–phosphate dehydrogenase and pyruvate kinase activities increase. These alterations indicate a shift from the glycogenotic state toward an increase in the pentose phosphate pathway and glycolysis. (Hepatology 1994;20:1162-1172).
Effects of insulin and IGF-1 on human hepatic stellate cells (HHSC): role of PI 3- and map-kinase pathways
Authors: G.Svegliati Baroni, F. Ridolfi, A. Casini, E. Bendia, A.M. Jezequel, A. Pontiroli, A. Benedetti, F. Folli
Journal: Journal of Hepatology (1998)
Acquired von Willebrand syndrome: An update
Authors: Massimo Franchini, Giuseppe Lippi
Journal: American Journal of Hematology (2006)

Abstract Acquired von Willebrand syndrome (aVWS) is a rare bleeding disorder with laboratory findings similar to those for congenital von Willebrand disease (VWD). However, unlike congenital VWD, it arises in individuals with no personal or family history of bleeding. aVWS occurs in association with a variety of underlying disorders, most frequently in lymphoproliferative disorders, myeloproliferative disorders, and cardiovascular diseases. Through an analysis of the more recent literature data, the pathophysiology and the clinical, laboratory, and therapeutic aspects of this syndrome are concisely reported in this review. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.
Novel β‐thalassemia trait (IVS I‐1 G→C) in a Japanese family
Authors: Noriko Fujihara, Minoru Tozuka, Ichiro Ueno, Kazuyoshi Yamauchi, Ritsuko Nakagoshi, Shinsuke Ishikawa, Masako Hirota, Nobuo Okumura, Eizaburo Ishii, Tsutomu Katsuyama
Journal: American Journal of Hematology (2002)

Abstract A rare β‐thalassemia mutation at the splicing junction [namely, G→C in intervening sequence (IVS) I‐1] was found in a Japanese family. The proband and his mother were heterozygous for the mutation. Analysis of mRNA extracted from the reticulocyte‐rich fraction obtained from the proband's mother revealed that the mutant β‐globin gene did not produce any detectable, stable mRNA including exon 1 and exon 2, since the polymorphism in exon 1 on her mutant gene was not detected in the RT‐PCR products. Am. J. Hematol. 72:64–66, 2003. © 2002 Wiley‐Liss, Inc.
Lenalidomide does not increase AML progression risk in RBC transfusion-dependent patients with Low- or Intermediate-1-risk MDS with del(5q): a comparative analysis
Authors: A Kuendgen, M Lauseker, A F List, P Fenaux, A A Giagounidis, N A Brandenburg, J Backstrom, A Glasmacher, J Hasford, U Germing
Journal: Leukemia (2012)

Data comparing long-term outcomes in lenalidomide-treated and untreated patients with myelodysplastic syndromes (MDS) with del(5q) are limited. We evaluated clinical outcomes of 295 lenalidomide-treated patients from two clinical trials (MDS-003 and MDS-004) and 125 untreated red blood cell (RBC) transfusion-dependent patients with del(5q) Low- or Intermediate-1 (Int-1)-risk MDS from a large multicenter registry. Risk factors for acute myeloid leukemia (AML) progression and mortality were assessed using Cox proportional hazards models with left truncation to adjust for study entry differences between cohorts. Baseline characteristics were well balanced across cohorts, except for a higher RBC transfusion burden in lenalidomide-treated patients (median, 6 vs 2 units/8 weeks). Median follow-up was 4.3 years from first dose for lenalidomide-treated patients and 4.6 years from diagnosis for untreated patients. Two-year cumulative AML progression incidences were 6.9% (95% confidence interval (CI): 3.3-13.9) and 12.1% (95% CI: 7.0-20.3) and 2-year overall survival (OS) probabilities were 89.9% (95% CI: 84.1-96.0) and 74.4% (95% CI: 66.1-83.7), respectively. AML progression risk was similar in both cohorts (hazard ratio (HR) 0.969, P=0.930); however, lenalidomide treatment was associated with significant improvement in survival (HR 0.597, P=0.012), after adjusting for all other covariates. In conclusion, lenalidomide treatment does not increase AML progression risk, but instead confers a possible survival benefit in RBC transfusion-dependent patients with del(5q) Low- or Int-1-risk MDS.
Sinus node dysfunction and hyperpolarization-activated (HCN) channel subunit remodeling in a canine heart failure model
Authors: S ZICHA, M FERNANDEZVELASCO, G LONARDO, N LHEUREUX, S NATTEL
Journal: Cardiovascular Research (2005)

Background: The hyperpolarization-activated cation current If contributes significantly to sinoatrial node pacemaker function and possibly to ectopic arrhythmogenesis. Little is known about the expression of corresponding hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits in normal hearts and HCN remodeling by diseases, like congestive heart failure (CHF), associated with disturbances of cardiac rhythm. Methods and results: We assessed expression of HCN1, 2 and 4 in normal mongrel dogs and dogs subjected to 2-week ventricular tachypacing-induced CHF. Competitive RT-PCR, Western blot and immunohistochemistry were used to quantify HCN subunit mRNA and protein expression in the right atrium (RA) and sinoatrial node. CHF approximately doubled sinus node recovery time, indicating suppressed sinus node pacemaker function. HCN expression under control conditions was HCN4>HCN2≫HCN1. HCN2 and HCN4 expression was greater at both protein and mRNA levels in sinoatrial node than RA. CHF significantly decreased sinus node HCN expression at both mRNA and protein levels (HCN2 by 78% and 82%; HCN4 by 42% and 77%, respectively). RA HCN2 expression was unaltered by CHF, but HCN4 was significantly upregulated (by 209%). Conclusions: HCN4 is the dominant subunit in canine sinoatrial node and RA; strong sinus node HCN expression likely contributes to its pacemaker function; downregulation of HCN4 and HCN2 expression contribute to CHF-induced sinus node dysfunction; and upregulation of atrial HCN4 may help to promote atrial arrhythmia formation. These findings provide novel information about the molecular basis of normal and disease-related impairments of cardiac impulse formation.
Allergenicity and antigenicity of wild-type and mutant, monomeric, and dimeric carrot major allergen Dau c 1: Destruction of conformation, not oligomerization, is the roadmap to save allergen vaccines
Authors: Gerald Reese, Barbara K. Ballmer-Weber, Andrea Wangorsch, Stefanie Randow, Stefan Vieths
Journal: Journal of Allergy and Clinical Immunology (2007)
Increased sensitivity of the denervated transplanted human heart to isoprenaline both before and after beta-adrenergic blockade.
Authors: S Yusuf, S Theodoropoulos, C J Mathias, N Dhalla, J Wittes, A Mitchell, M Yacoub
Journal: Circulation (1987)

It is not known whether surgical denervation leads to increased beta-receptor sensitivity after human cardiac transplantation. We assessed cardiac beta-receptor sensitivity by studying the heart rate response to isoprenaline of the denervated donor heart as compared with the innervated recipient heart in eight patients who underwent heterotopic cardiac transplantation and in six patients with orthotopic transplantation. Changes in the donor and recipient hearts seen in these 14 patients were further compared with those seen in 10 normal volunteers. Incremental intravenous infusion of isoprenaline (5, 10, and 15 ng/kg/min) raised heart rate to a greater extent in the donor compared with the recipient hearts in the eight patients who had heterotopic grafts (slopes [beats/min/ng/kg]: donor = +2.26, recipient = +1.59; p less than .01). In addition, the donor hearts of the transplant patients were more sensitive than hearts of the normal volunteers (slopes: donor = +2.26, normal = +0.94; p less than .01). The changes in the two groups of donor hearts were similar (slopes: orthotopic = +2.24, heterotopic = +2.27; NS). The recipient hearts in the patients with heterotopic transplants were more sensitive than the hearts of the normal volunteers (p less than .05), suggesting that the observed differences in isoprenaline sensitivity in the patients with heterotopic grafts were not caused by a decreased sensitivity of the recipient heart. After beta-blockade, the heart rate responses to isoprenaline were attenuated to the same extent in denervated and innervated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
The stimulation of hair growth in the flank organs of female hamsters by subcutaneous testosterone propionate and its inhibition by topical cyproterone acetate: dose-response studies
Authors: EDWIN KASZYNSKI
Journal: British Journal of Dermatology (1983)

A dose-dependent increase in the mass of flank organ hair was produced in 11-week-old female hamsters by subcutaneously injected testosterone propionate. The mass of androgen-stimulated flank organ hair was decreased bilaterally in a dose-dependent manner by cyproterone acetate applied topically to one flank organ of each hamster.
Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats
Authors: Marina Fernández, Maria Bianchi, Victoria Lux-Lantos, Carlos Libertun
Journal: Environmental Health Perspectives (2009)

Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins, and polystyrene and is found in many products. Several reports have revealed potent in vivo effects, because BPA acts as an estrogen agonist and/or antagonist and as an androgen and thyroid hormone antagonist.We analyzed the effects of neonatal exposure to BPA on the reproductive axis of female Sprague-Dawley rats.Female rats were injected subcutaneously, daily, from postnatal day 1 (PND1) to PND10 with BPA [500 microg/50 microL (high) or 50 microg/50 microL (low)] in castor oil or with castor oil vehicle alone. We studied body weight and age at vaginal opening, estrous cycles, and pituitary hormone release in vivo and in vitro, as well as gonadotropin-releasing hormone (GnRH) pulsatility at PND13 and in adults. We also analyzed two GnRH-activated signaling pathways in the adults: inositol-triphosphate (IP(3)), and extracellular signal-regulated kinase(1/2) (ERK(1/2)).Exposure to BPA altered pituitary function in infantile rats, lowering basal and GnRH-induced luteinizing hormone (LH) and increasing GnRH pulsatility. BPA dose-dependently accelerated puberty onset and altered estrous cyclicity, with the high dose causing permanent estrus. In adults treated neonatally with BPA, GnRH-induced LH secretion in vivo was decreased and GnRH pulsatility remained disrupted. In vitro, pituitary cells from animals treated with BPA showed lower basal LH and dose-dependently affected GnRH-induced IP(3) formation; the high dose also impaired GnRH-induced LH secretion. Both doses altered ERK(1/2) activation.Neonatal exposure to BPA altered reproductive parameters and hypothalamic-pituitary function in female rats. To our knowledge, these results demonstrate for the first time that neonatal in vivo BPA permanently affects GnRH pulsatility and pituitary GnRH signaling.
Nitrogen Dioxide--Induced Respiratory Illness in Ice Hockey Players-Reply
Authors: K. Hedberg, K. L. MacDonald, M. Osterholm, C. Hedberg, K. White
Journal: JAMA (1990)

<h3>In Reply.—</h3> We thank Drs Ford and Rothman for their interest in our article and their comments regarding statistical analysis of the pulmonary function data. In our analysis, we used a Mann-Whitney<i>U</i>rank-sum test to compare the median values of observed lung-function parameters between the two hockey teams and the comparison group. We also analyzed the data using a multiple logistic regression model that controlled for height, weight, and age. No statistically significant differences in pulmonary function were found between the two exposure groups and thecontrol group initially or at follow-up testing by either method of analysis. These tests were used because they allowed us to compare the distributions of lung-function parameters between the groups, rather than the proportions of each group performing below an arbitrary threshold value. Also, we did not combine the players with single and multiple (chronic) exposures in the analysis because we believe that
Introduction of Sodium Diphenyl Hydantoinate
Authors: Maurice W. Van Allen
Journal: JAMA (1984)

Had the discovery of the anticonvulsant properties of sodium diphenyl hydantoinate been fortuitous, an article first reporting the effectiveness of this drug in man would justify its inclusion as a landmark article in the centennial celebration issues of<i>JAMA</i>. This drug, now called<i>phenytoin</i>(Dilantin), soon revolutionized the drug treatment of the convulsive disorders when such treatment had been largely limited to the bromides and phenobarbital. Phenytoin remains today a mainstay of therapy in the control of major motor seizures and some other manifestations of epilepsy. Few drugs continue in active use in unmodified form 45 years after the discovery of their usefulness. Few drugs have been as important for the relief of human disability and suffering, and this with an acceptable level of side and toxic effects in most patients. That phenytoin was chosen by logical inference to be included in a series of drugs actively tested for effectiveness
Venom Immunotherapy in Hymenoptera Sting Allergy
Authors: U. Thurnheer, U. Müller, R. Stoller, A. Lanner, R. Hoigne
Journal: Allergy (1983)

42 patients with confirmed hypersensitivity to honey bee (HBV) and/or yellow jacket (YJV) were treated with the respective venoms (7 with HBV, 5 with YjV and 30 with both venoms). Treatment tolerance, skin tests (ST), specific IgE‐ and specific IgG‐antibodies were monitored before, after 3, 6, 12, 24 and 36 months. 21 patients had ash and 21 a conventional treatment schedule. Maintenance dose was 100 μg. Adverse effects occurred as large local (8 patients), slight systemic (12 patients) and moderate to severe systemic reactions (4 patients). Of 24 re‐exposed patients 17 had no reaction at all, six a markedly decreased and one an unchanged reaction. After 3 years of treatment ST became negative in nine of 31 patients on HBV and in seven of 26 patients on YJV. RAST became negative in three of 30 patients on HBV and 17 of 29 patients on YJV treatment. Both ST and RAST became negative in five HBV‐ and 10 YJV‐treated patients. Loss of venom hypersensitivity according to diagnostic tests may correspond to actual desensitization and enable discontinuation of immunotherapy.
Histocompatibility Testing 1965
Authors: J. Wayne Streilein
Journal: JAMA (1966)

The second international symposium on histocompatibility testing, which was held in Leiden, the Netherlands, in August 1965, emphasized the serological methods of determining histocompatibility antigens in man. This book is a literal account of the symposium, including a summary of the workshop which followed. Since Dausset et al described isoantibodies in human sera capable of agglutinating human peripheral blood leukocytes, an entire discipline has emerged based on the hypothesis that (a) these antibodies are directed against specific antigens on the various white cell types, and (b) some of these antigens are, or are closely related to, transplantation antigens—those responsible for the induction of specific homograft immunity. Despite the brief interval that has elapsed since these original observations, many leukocyte antigenic systems have been identified in man. Dr. van Rood's group has described at least seven different antigenic systems detected by "monospecific" antisera obtained from multiparous females and oft-transfused patients. Similar
DISSOCIATION BETWEEN FILTERED LOAD OF SODIUM AND ITS RATE OF EXCRETION IN THE URINE*
Authors: William B. Blythe, Louis G. Welt
Journal: Journal of Clinical Investigation (1963)

Sodium appearing in the urine presumably represents the difference between the amount filtered at the glomerulus and that which leaves the tubular lumen as the filtrate courses through the nephron.The rate of urinary sodium excre- tion (UNaV) can be modified, therefore, by changes in the filtered load [glomerular filtration rate (GFR) x plasma sodium concentration (PNa)], or the degree of tubular reabsorption, or both.Since UNaV under most circumstances repre- sents only about 1%1o of the filtered load, it is evi-
"Works But Not Words."
Authors: F. R. Smyth
Journal: JAMA (1905)

Bismarck, N. D., June 3, 1905. <h3>To the Editor:</h3> I failed to see Mr. Bok's letter inThe Journal, May 20, 1905. until my attention was drawn to it at the meeting of the House of Delegates of our state association. Mr. Bok complains of the apathy of individual physicians and medical societies in not appearing before legislative committees on behalf of pure-drug laws, introduced in different legislatures last winter, and states that within his own knowledge not a single physician or representative of a medical society appeared before such a committee. While this may be true generally, it does not apply in this state to the bill introduced and passed in our legislature, prohibiting the adulteration of drugs and providing for the printing of the ingredients, in case of poisons and other dangerous substances, on the labels of proprietary medicines. My attention was first drawn to this bill when
Funding Subspecialty Training for Clinical Investigators
Authors: David G. Nathan
Journal: New England Journal of Medicine (1987)

Recently, a task force on academic health centers, appointed by the Commonwealth Fund, has offered a "prescription for change" with a laudable goal — "to preserve the functions of academic health centers for the future" in the United States.1 The first report of the task force deals with graduate medical education and responds primarily to what is currently perceived as an excess of medical and surgical subspecialists in practice and in the pipeline. The task force argues for a voucher system that would restrict reimbursement for graduate medical education to three years for pediatricians and internists and five years for . . .
Treatment of Alcoholism
Authors: Eric C. Kast
Journal: JAMA (1976)

To the Editor.—  In a recent commentary (235:2103,1976), Marvin A. Block, MD, deplores the development of a new treatment method in which alcoholic patients can be taught to drink without slipping into further dependence.  Current treatment of alcoholism is far from successful, and its theoretical basis is rather obscure—psychologically and medically.  Some established methods tend to injure the patient's self-esteem, and thus contribute to the constellation that causes the symptoms known as alcoholism.  The first thing to be sought in a new method of treating this symptom is a way of respecting the patient's personal dignity and attempting to increase his self-respect, which has already been severely damaged by his disease.  Dr Block has confused the necessity for respecting the patient's dignity and autonomy with  as a social necessity.  The ways in which the use of alcohol reflects the problem of our society are beyond the scope of this
882. Development of a Transposon-Based Approach to Identification of Novel Transgene Insertion Sites within Replicating Viral Genomes
Authors: Peter Kretschmer, Fang Jin, Cecile Chartier, Paul Harden, Terry Hermiston
Journal: Molecular Therapy (2005)

Oncolytic viruses represent a potentially new treatment for cancer. It is clear, however, that the potency of these agents must be increased, and one approach is to incorporate therapeutic genes that synergise with the lytic functions of the virus. For Ad5, the choice of insertion site(s) is generally limited to a few known non-essential regions for viral DNA replication. Additional less well characterized replication-competent viruses are being developed for cancer therapies, and in these cases extensive research will be needed to characterize insertion sites that are compatible with optimal viral replication. Consequently, we have developed a technology that enables a non-prejudiced scanning of entire viral genomes to identify sites for insertions of transgene expression cassettes without affecting viral replication.
The Myometrium and Uterine Cervix in Normal and Preterm Labor
Authors: Gabor Huszar, Frederick Naftolin
Journal: New England Journal of Medicine (1984)

PRETERM labor remains the most important cause of perinatal morbidity and mortality. In this article we review our present understanding of the biochemistry and physiology of the myometrium and uterine cervix, particularly as they relate to the pathogenesis and therapy of preterm labor.During pregnancy, the myometrium relaxes to accommodate the developing infant and products of conception, and at the end of pregnancy, it provides the rhythmic tonic contractions of labor that facilitate expulsion of the uterine contents. As in all muscle tissue, myometrial contractility is based on the interaction of the contractile proteins actin and myosin. Many, if not . . .