tbuckley/cabot-search huggingface dataset:
The effect of hepatic stimulatory substance, isolated from regenerating hepatic cytosol, and 50,000 and 300,000 subfractions in enhancing survival in experimental acute hepatic failure in rats treated with D-galactosamine
Authors: Antonio Francavilla, Alfredo Dileo, Lorenzo Polimeno, Judith Gavaler, Riccardo Pellicci, Satoro Todo, Igal Kam, John Prelich, Leonard Makowka, Thomas E. Starzl
Journal: Hepatology (1986)

Galactosamine induces a dose-dependent hepatic injury in rats and many other animals. The toxicity of D-galactosamine appears to be a consequence of the loss of hepatic UTP. It has previously been reported that regenerating liver cytosol is able to prevent, at least in part, the lethal effect of this substance by stimulating hepatic regeneration. Recently, we have separated a fraction using alcohol precipitation (80%) from regenerating liver cytosol and from weanling rat liver cytosol prepared in acetate buffer (100 mM, pH 6.5). We named this fraction hepatic stimulatory substance because of its ability to stimulate DNA synthesis in vivo when injected intraperitoneally in 40% hepatectomized rats and in vitro in the presence of hepatocytes isolated and maintained in monolayer cultures. The stimulatory activity of the hepatic stimulatory substance is fully evident in subfractions of molecular weight up to 300,000 and 50,000 daltons of the crude material obtained using Amicon Ultra membrane filters. The present report describes the ability of hepatic stimulatory substance and its subfractions to stimulate hepatocyte proliferation and the application of these hepatic extracts in successfully reversing the lethality of D-galactosamine-induced hepatic necrosis in rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Loss of the <i>CBX7</i> Gene Expression Correlates with a Highly Malignant Phenotype in Thyroid Cancer
Authors: Pierlorenzo Pallante, Antonella Federico, Maria Teresa Berlingieri, Mimma Bianco, Angelo Ferraro, Floriana Forzati, Antonino Iaccarino, Maria Russo, Giovanna Maria Pierantoni, Vincenza Leone, Silvana Sacchetti, Giancarlo Troncone, Massimo Santoro, Alfredo Fusco
Journal: Cancer Research (2008)

Abstract Using gene expression profiling, we found that the CBX7 gene was drastically down-regulated in six thyroid carcinoma cell lines versus control cells. The aims of this study were to determine whether CBX7 is related to the thyroid cancer phenotype and to try to identify new tools for the diagnosis and prognosis of thyroid cancer. We thus evaluated CBX7 expression in various snap-frozen and paraffin-embedded thyroid carcinoma tissues of different degrees of malignancy by quantitative reverse transcription-PCR and immunohistochemistry, respectively. CBX7 expression progressively decreased with malignancy grade and neoplasia stage. Indeed, it decreased in an increasing percentage of cases going from benign adenomas to papillary (PTC), follicular, and anaplastic (ATC) thyroid carcinomas. This finding coincides with results obtained in rat and mouse models of thyroid carcinogenesis. CBX7 loss of heterozygosity occurred in 36.8% of PTC and in 68.7% of ATC. Restoration of CBX7 expression in thyroid cancer cells reduced growth rate, with a retention in the G1 phase of the cell cycle, suggesting that CBX7 can contribute to the proliferation of the transformed thyroid cells. In conclusion, loss of CBX7 expression correlates with a highly malignant phenotype in thyroid cancer patients. [Cancer Res 2008;68(16):6770–8]
Phase I and Pharmacokinetic Study of MS-275, a Histone Deacetylase Inhibitor, in Patients With Advanced and Refractory Solid Tumors or Lymphoma
Authors: Qin C. Ryan, Donna Headlee, Milin Acharya, Alex Sparreboom, Jane B. Trepel, Joseph Ye, William D. Figg, Kyunghwa Hwang, Eun Joo Chung, Anthony Murgo, Giovanni Melillo, Yusri Elsayed, Manish Monga, Mikhail Kalnitskiy, James Zwiebel, Edward A. Sausville
Journal: Journal of Clinical Oncology (2005)

Purpose The objective of this study was to define the maximum-tolerated dose (MTD), the recommended phase II dose, the dose-limiting toxicity, and determine the pharmacokinetic (PK) and pharmacodynamic profiles of MS-275. Patients and Methods Patients with advanced solid tumors or lymphoma were treated with MS-275 orally initially on a once daily × 28 every 6 weeks (daily) and later on once every-14-days (q14-day) schedules. The starting dose was 2 mg/m 2 and the dose was escalated in three- to six-patient cohorts based on toxicity assessments. Results With the daily schedule, the MTD was exceeded at the first dose level. Preliminary PK analysis suggested the half-life of MS-275 in humans was 39 to 80 hours, substantially longer than predicted by preclinical studies. With the q14-day schedule, 28 patients were treated. The MTD was 10 mg/m 2 and dose-limiting toxicities were nausea, vomiting, anorexia, and fatigue. Exposure to MS-275 was dose dependent, suggesting linear PK. Increased histone H3 acetylation in peripheral-blood mononuclear-cells was apparent at all dose levels by immunofluorescence analysis. Ten of 29 patients remained on treatment for ≥ 3 months. Conclusion The MS-275 oral formulation on the daily schedule was intolerable at a dose and schedule explored. The q14-day schedule is reasonably well tolerated. Histone deacetylase inhibition was observed in peripheral-blood mononuclear-cells. Based on PK data from the q14-day schedule, a more frequent dosing schedule, weekly × 4, repeated every 6 weeks is presently being evaluated.
Long-term home care programmes may reduce hospital admissions in COPD with chronic hypercapnia
Authors: E Clini, M Vitacca, K Foglio, P Simoni, N Ambrosino
Journal: European Respiratory Journal (1996)

Long-term oxygen therapy (LTOT) has been shown to improve survival in chronic obstructive pulmonary disease (COPD) patients. The clinical effectiveness of long-term home mechanical ventilation (HMV) is still discussed, nevertheless both LTOT and HMV are often included in the home care programmes of these patients. To evaluate the effectiveness of home care programmes including either HMV or LTOT, 34 COPD patients were studied. They were admitted to either HMV (Group A: 12 males and 5 females, aged 62 +/- 5 yrs), or LTOT (Group B: 9 males and 8 females, aged 62 +/- 8 yrs). They were compared to a historical group (Group C: 19 males and 10 females, aged 67 +/- 16 yrs) performing only their usual standard LTOT during the same period. Spirometry, maximal inspiratory pressure and arterial blood gas values were assessed at baseline and at 6, 12 and 18 months of follow-up. Mortality rate and number of hospital and intensive care unit (ICU) admissions and days of hospitalization were also assessed. Four out of 17 (23%) patients in Group A, 3 out of 17 (18%) in Group B, and 5 out of 29 (17%) in Group C died within 18 months. Of the lung function tests, only maximal inspiratory pressure in Group A showed a significant increase in the 18th month (50 +/- 4 to 56 +/- 7 cmH2O; p<0.01). In comparison to 18 months prior to the study, hospital admissions (from 2.2 +/- 0.6 to 1.3 +/- 1.1 and from 2.0 +/- 0.7 to 1.0 +/- 0.9 for Group A and B, respectively; p<0.005 for both), and days of hospitalization (from 60 +/- 34 to 34 +/- 40 and from 55 +/- 23 to 18 +/- 20 days in Group A and B, respectively; p<0.005 for both) significantly decreased only in the two groups submitted to the home care programme. We conclude that home care programmes may be effective in the long-term treatment of chronically hypercapnic chronic obstructive pulmonary disease patients in reducing hospital admissions.
The Importance of Postapproval Data for Dabigatran
Authors: Rita F. Redberg
Journal: JAMA Internal Medicine (2014)

Dabigatran was approved by the Food and Drug Administration (FDA) in 2010via theacceleratedpathwayafter a6-month review. The haste to approve novel drugs places an increasing importance on postapproval data to help better understand risks and benefits. Thus, the postapproval data on the use of dabigatran in the Medicare population are informative in alerting us to risks associated with real-world use. Hernandez et al1 give us cause for concern because it appears that the bleeding risk for dabigatran ishigher than forwarfarinandsignificantlygreater than originallyappearedat the timeof theFDAapproval.Thesedata conflictwith the recentMini-Sentinel analysis from theFDA.2 The authors note that the FDA failed to adjust for differences in patient characteristics, which would bias the results. This study remindsusof the importanceofpostmarketingdata and ofhaving adequatedataon risks andbenefits to advise ourpatients accurately.
Chondrocalcinosis Articularis: Section II. Genetic Study
Authors: J. Valsik, D. Zitnan, S. Sit'Aj
Journal: Annals of the Rheumatic Diseases (1963)

All general practitioners on the list of a single executive council were contacted and 91% were interviewed. They were asked about the type of family planning service currently provided and their willingness to extend the service. Only 3% said that they were not providing any service at the time of interview, but only 4% stated that they provided a complete range of techniques to all patients; almost two thirds of practitioners only provided advice and the “pill”. Lack of training in family planning techniques emerged as the most important factor in determining the type of service provided. At the time of interview 64% of doctors stated that they would like further training, and 35% of all doctors asked for a full course of clinical training. Many general practitioners (81%) were willing to extend their family planning services but 65% wanted financial reimbursement and 50% needed additional administrative support as prerequisites.
Identification of the Major Steps in Botulinum Toxin Action
Authors: Lance L. Simpson
Journal: The Annual Review of Pharmacology and Toxicology (2004)

Botulinum toxin is a uniquely potent substance synthesized by the organisms Clostridium botulinum, Clostridium baratii, and Clostridium butyricum. This toxin, which acts preferentially on peripheral cholinergic nerve endings to block acetylcholine release, is both an agent that causes disease (i.e., botulism) as well as an agent that can be used to treat disease (e.g., dystonia). The ability of botulinum toxin to produce its effects is largely dependent on its ability to penetrate cellular and intracellular membranes. Thus, toxin that is ingested or inhaled can bind to epithelial cells and be transported to the general circulation. Toxin that reaches peripheral nerve endings binds to the cell surface then penetrates the plasma membrane by receptor-mediated endocytosis and the endosome membrane by pH-induced translocation. Internalized toxin acts in the cytosol as a metalloendoprotease to cleave polypeptides that are essential for exocytosis. This review seeks to identify and characterize all major steps in toxin action, from initial absorption to eventual paralysis of cholinergic transmission.
P11.06 * LYMPHOMATOSIS CEREBRI: A RARE FORM OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: C. Izquierdo, R. Velasco, N. Vidal, N. Sola, S. Llufriu, J. Sanchez, S. Besora, R. Nakayama, F. Graus, J. Bruna
Journal: Neuro-Oncology (2014)

INTRODUCTION: Primary central nervous system lymphomas (PCNSL) are a unusual form of non-Hodgkin lymphoma, restricted to the neuroaxis and eyes.In most cases magnetic resonance imaging (MRI) disclose single or multiples lesions with mass effect and contrast enhancement. Rarely,PCNSL may occur as a diffuse non enhanced infiltrative lesion, a variant called Lymphomatosis Cerebri (LC).LC can present with a progressive course and diffuse white matter abnormalities on MRI what includes a wide differential diagnosis, becoming a diagnostic challenge. OBJECTIVE: To present the detailed characteristics of 4 patients who were diagnosed of LC at our centers and analyze the results of a systematic review of this entity. MATERIAL AND METHODS: A systematic literature search was carried out using Pubmed an ISI Web of knowledge to 1 February 2014.The search also included reference lists of papers identified. Demographic, clinical, histological, cerebrospinal fluid (CSF), MRI and therapeutic data were extracted. Patients with nodular enhancement at first MRI or concurrent systemic lymphoma were excluded. RESULTS: 28 patients from literature and 4 new patients were included. The median age was 58.5 years old (29-80).53.1% of patients were women. Only 1 was not inmunocompetent.62.5% out of patients presented with a Karnofsky Performance Status (KPS) <70. Most common presenting symptoms were cognition impairment (59.4%) and behavioral changes (50%).18.8% developed seizures. First MRI showed patchy enhancement in 33.3% of patients. Nearly half of patients (48.6%) had infratentorial and supratentorial infiltration. Both hemispheres were infiltrated in 96.8% of cases. Spinal cord was affected in 2 patients. CSF results were normal in 18.8% of patients. The median time to diagnosis was 150 days (30-900). Diagnosis was postmortem in 35.5% of patients. Treatments administered included: only corticoids (34.4%), chemotherapy and/or radiotherapy (46.9%). Median overall survival was 248 days (80-1890). According treatment, median survival was 3, 6.9, 44.3 months in no treated, only receiving corticoids and treated with chemotherapy/radiotherapy patients, respectively. One third of all patients were alive 1 year after the onset of the illness. Univariate analysis revealed that age ≥ 59 years (p = 0.029), KPS < 70 (p = 0.01), hypoglycorrhachia (p < 0.001) and lack of chemotherapy and/or radiotherapy treatment (p = 0.02) were associated with worst prognosis.The multivariate analysis demonstrated that KPS was the only independent prognostic factor for survival (HR: 0.65; ( CI95%:0.004-0.946); p = 0.045). CONCLUSION: LC is frequently misdiagnosed and associated with a considerable diagnostic delay that could explain the low performance status of patients at diagnosis. Despite to the fact that some patients can respond to the oncologic treatment, KPS is the only independent prognostic factor identified.
Risk of primary biliary liver cirrhosis in patients with coeliac disease: Danish and Swedish cohort data
Authors: H T Sørensen, A M Thulstrup, P Blomqvist, B Nørgaard, K Fonager, A Ekbom
Journal: Gut (1999)

BACKGROUND Several case reports, but only a few studies, have examined the coexistence of coeliac disease and primary biliary cirrhosis. AIM To estimate the risk of primary biliary cirrhosis in two national cohorts of patients with coeliac disease in Denmark and Sweden. METHODS Through record linkage all Danish patients hospitalised with coeliac disease were followed for possible occurrence of primary biliary cirrhosis from 1 January 1977 until 31 December 1992. All patients hospitalised with coeliac disease in Sweden from 1987 to 1996 were also followed in a separate analysis. RESULTS A total of 896 patients with coeliac disease were identified in Denmark with a median follow up period of 9.1 years for a total of 8040 person-years at risk. Two cases of primary biliary cirrhosis were observed where 0.07 were expected, giving a standardised incidence ratio of 27.6 (95% confidence interval 2.9 to 133.5). A total of 7735 patients with coeliac disease were identified in Sweden with a median follow up period of 5.1 years for a total of 39 284 person-years at risk. Twenty two people with primary biliary cirrhosis were identified compared with 0.88 expected, giving a standardised incidence ratio of 25.1 (95% confidence interval 15.7 to 37.9). CONCLUSION Patients with coeliac disease are at increased risk of having primary biliary cirrhosis.
Identification and Characterization of Pkhd1, the Mouse Orthologue of the Human ARPKD Gene
Authors: Yasuyuki Nagasawa, Sonja Matthiesen, Luiz F. Onuchic, Xiaoying Hou, Carsten Bergmann, Ernie Esquivel, Jan Senderek, Zhiyong Ren, Raoul Zeltner, Laszlo Furu, Ellis Avner, Markus Moser, Stefan Somlo, Lisa Guay-Woodford, Reinhard Büttner, Klaus Zerres, Gregory G. Germino
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. PKHD1, the gene mutated in human autosomal recessive polycystic kidney disease has recently been identified. Its translation products are predicted to belong to a superfamily of proteins involved in the regulation of cellular adhesion and repulsion. One notable aspect of the gene is its unusually complex pattern of splicing. This study shows that mouse Pkhd1 and its translation products have very similar properties to its human orthologue. Mouse Pkhd1 extends over approximately 500 kb of genomic DNA, includes a minimum of 68 nonoverlapping exons, and exhibits a complex pattern of splicing. The longest ORF encodes a protein of 4059aa predicted to have an N-terminal signal peptide, multiple IPTs and PbH1 repeats, a single transmembrane span (TM), and a short cytoplasmic C-terminus. Although the protein sequence is generally well conserved (approximately 73% average identity), the C-termini share only 55% identity. The pattern of Pkhd1 expression by in situ hybridization was also examined in developing and adult mouse tissues over a range of ages (E12.5 to 3 mo postnatal). High levels of expression were present in renal and biliary tubular structures at all time points examined. Prominent Pkhd1 signals were also found in a number of other organs and tissues. Tissue-specific differences in transcript expression were revealed through the use of single exon probes. These data show that key features of human PKHD1 are highly conserved in the mouse and suggest that the complicated pattern of splicing is likely to be functionally important.
Racial Differences in Prognostic Value of Adult Height for Biochemical Progression Following Radical Prostatectomy
Authors: Stephen J. Freedland, William J. Aronson, Bruce Trock, Pinchas Cohen, Christopher J. Kane, Christopher L. Amling, Joseph C. Presti, Martha K. Terris
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Adult height, as a surrogate of childhood and adolescent hormone activity and diet, has been associated with the risk for development and death from prostate cancer in predominantly White populations. However, hormonal activity and diets vary between races. We examined whether height was significantly associated with biochemical progression following radical prostatectomy and whether there was an interaction between height and race. Experimental Design: Multivariate Cox proportional hazards analysis was used to determine if height significantly predicted biochemical progression among 1,503 men (450 Black and 1,053 White) treated with radical prostatectomy between 1988 and 2003. We examined for possible interactions between height and race. Results: Taller men (&amp;gt;175.3 cm) were significantly younger (P = 0.001), treated in more recent years (P = 0.02), had more clinical stage T1 disease (P = 0.001), and were less likely to have extraprostatic extension (P = 0.02) than shorter men (≤175.3 cm). Height was not significantly related to race, preoperative serum prostate-specific antigen concentrations, biopsy or pathologic Gleason sum, positive surgical margins, seminal vesicle invasion, or lymph node metastasis. Height was significantly associated with progression among Black men [relative risk (RR), 1.67; 95% confidence interval (95% CI), 1.00-2.79] but not among White men (RR, 1.03; 95% CI, 0.77-1.38). The interaction between race and height for predicting biochemical progression was statistically significant (Pinteraction = 0.05). Conclusions: There was an interaction between height and race in that height predicted progression for Black men but not for White men. The explanation for these findings is unclear, although lower insulin-like growth factor–binding protein-3 concentrations among Black men may be involved.
Differential effects of the optical isomers of EMD 53998 on contraction and cytoplasmic Ca2+ in isolated ferret cardiac muscle.
Authors: J White, J A Lee, N Shah, C H Orchard
Journal: Circulation Research (1993)

EMD 53998 (a thiadiazinone) is a novel inotropic substance that increases the Ca2+ sensitivity of the myofilaments in skinned cardiac fibers and has been found to have similar effects in intact cardiac muscle. However, the compound also possesses the ability to inhibit phosphodiesterase III, indicating that its actions in intact cardiac muscle are likely to be complex. The present study was carried out to investigate the possibility that the optical isomers of EMD 53998--(+)EMD 57033 and (-)EMD 57439--which have recently been shown to possess a separation of sensitization and phosphodiesterase inhibition in subcellular preparations, might also demonstrate this separation of activities in intact cardiac muscle. The experiments were performed on isolated ferret papillary muscles, which were contracting isometrically. In some preparations, the photoprotein aequorin was injected into superficial cells to measure intracellular Ca2+ as well as force. (+)EMD 57033 caused a substantial positive inotropic effect that was associated with prolongation of the twitch, reduction in the amplitude of the Ca2+ transient, and abbreviation of the Ca2+ transient. This is the profile expected of a Ca(2+)-sensitizing compound. Conversely, (-)EMD 57439 caused a less marked positive inotropic effect that was associated with an abbreviation of the twitch, an increase in the amplitude of the Ca2+ transient, and an abbreviation of the Ca2+ transient. This is the profile expected of an agent producing its inotropic effect by increasing cAMP (e.g., phosphodiesterase inhibition). The results indicate that the optical isomers of EMD 53998 possess a remarkable separation of Ca(2+)-sensitizing and phosphodiesterase-inhibiting activities in intact cardiac muscle. These actions were additive and could account for the effects observed with EMD 53998. (+)EMD 57033 appears to be the first inotropic agent that acts predominantly by increasing myofilament calcium sensitivity.
Critical analysis of the stringent complete response in multiple myeloma: contribution of sFLC and bone marrow clonality
Authors: Joaquín Martínez-López, Bruno Paiva, Lucía López-Anglada, María-Victoria Mateos, Teresa Cedena, María-Belén Vidríales, María Auxiliadora Sáez-Gómez, Teresa Contreras, Albert Oriol, Inmaculada Rapado, Ana-Isabel Teruel, Lourdes Cordón, María Jesús Blanchard, Enrique Bengoechea, Luis Palomera, Felipe de Arriba, Cecilia Cueto-Felgueroso, Alberto Orfao, Joan Bladé, Jesús F. San Miguel, Juan José Lahuerta
Journal: Blood (2015)
From Paul's predictions in the World Cup to the publication bias in genetic studies on complex traits
Authors: G. Zhang, P.N. LeSouëf
Journal: European Respiratory Journal (2010)

To the Editors:

Recently, the octopus Paul has attracted much attention through the general media by his accurate predictions in the FIFA 2010 World Cup. During the World Cup, Paul predicted the outcomes of eight matches with 100% success. Assuming that Paul has 50% accurate choices as independent coin flips, the probability for a continual eight success prediction is 0.0039. However, we may think that Octopus Paul is more likely to select the box with the German flag, for some reason. For example, when predicting the outcome of the Germany games Paul selected the box with the German flag five times out of seven, giving a percentage rating of 71.4% for selection of the German flag. Assuming Paul is more likely to select the German flag with a probability rate of 0.714, the probability for the correct predictions Paul achieved in FIFA 2010 World Cup is 0.0076 (0.714×0.714×0.714×0.714×0.714×0.286×0.286×0.5). In the academic world, we usually select a probability boundary of 0.05 or 0.01 to reject the null hypothesis 1. Therefore, we may conclude that Paul …