tbuckley/cabot-search huggingface dataset:
Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma
Authors: Shunsuke Ura, Masao Honda, Taro Yamashita, Teruyuki Ueda, Hajime Takatori, Ryuhei Nishino, Hajime Sunakozaka, Yoshio Sakai, Katsuhisa Horimoto, Shuichi Kaneko
Journal: Hepatology (2008)

MicroRNA (miRNA) plays an important role in the pathology of various diseases, including infection and cancer. Using real-time polymerase chain reaction, we measured the expression of 188 miRNAs in liver tissues obtained from 12 patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and 14 patients with hepatitis C virus (HCV)-related HCC, including background liver tissues and normal liver tissues obtained from nine patients. Global gene expression in the same tissues was analyzed via complementary DNA microarray to examine whether the differentially expressed miRNAs could regulate their target genes. Detailed analysis of the differentially expressed miRNA revealed two types of miRNA, one associated with HBV and HCV infections (n = 19), the other with the stage of liver disease (n = 31). Pathway analysis of targeted genes using infection-associated miRNAs revealed that the pathways related to cell death, DNA damage, recombination, and signal transduction were activated in HBV-infected liver, and those related to immune response, antigen presentation, cell cycle, proteasome, and lipid metabolism were activated in HCV-infected liver. The differences in the expression of infection-associated miRNAs in the liver correlated significantly with those observed in Huh7.5 cells in which infectious HBV or HCV clones replicated. Out of the 31 miRNAs associated with disease state, 17 were down-regulated in HCC, which up-regulated cancer-associated pathways such as cell cycle, adhesion, proteolysis, transcription, and translation; 6 miRNAs were up-regulated in HCC, which down-regulated anti-tumor immune response.miRNAs are important mediators of HBV and HCV infection as well as liver disease progression, and therefore could be potential therapeutic target molecules.
A Smallpox Epidemic
Authors: T. St. M. Norris
Journal: BMJ (1944)

An epidemic of smallpox occurring among naval personnel and (European) civilian Admiralty employees is here described.The greater severity and length of the primary epidemic occurring 'among the native population are demonstrated, and its progress would appear to illustrate the very great prognostic value that can be attached to the presence and size of scars of previous successful vaccination.Description of Outbreak Smallpox is endemic in the Eastern Mediterranean area.During the winter of 1943-4, from the middle of November onwards, the weekly notifications for civilian cases steadily rose (see Graph).The rise was noted by the naval health
THE MECHANISM OF ACTIVE CEREBRAL IMMUNITY TO EQUINE ENCEPHALOMYELITIS VIRUS
Authors: R. Walter Schlesinger
Journal: The Journal of Experimental Medicine (1949)

The fate of W.E.E. virus has been followed in the brains of mice vaccinated to such an extent that they failed to resist a large intracerebral challenge dose of a viral variant with a rapid rate of multiplication but were fully protected against a similar amount of a "slow" strain. The growth rate of the "fast" variant in vaccinated animals paralleled that in non-vaccinated ones at a slightly lower level. The "slow" strain also multiplied, but its rate of growth was depressed. Nevertheless, it persisted for 4 days at a level 100-fold higher than its initial titer. After the 4th day the virus was no longer demonstrable and was replaced by neutralizing antibody which rose so high that the serum antibody/brain antibody ratio was reduced from a "physiological" value of about 200/1 to less than 10/1. Antibody persisted in brain tissue in high titer until at least 127 days after challenge inoculation. The shift in the serum/brain ratio of neutralizing antibody was paralleled by a similar shift in the ratio of complement-fixing antibody. The neutralizing antibody in brain tissue, like that in serum, followed the "percentage law" on dilution of underneutralized mixtures. In mice immunized with small doses of vaccine, the intracerebral challenge inoculum induced a significantly greater local immune response than in those immunized to a higher degree. Mice with very low grade immunity were found more resistant to large amounts of virus than to small amounts. This "paradoxical" response to challenge was explained as due to the antigenic booster effect exerted by amounts of virus in excess of that utilized to initiate infection which were present in large inocula but absent in small doses. The broader relation of these findings to the problem of antiviral immunity has been discussed.
Ionic basis and analytical solution of the wenckebach phenomenon in guinea pig ventricular myocytes.
Authors: M Delmar, L Glass, D C Michaels, J Jalife
Journal: Circulation Research (1989)

The ionic mechanisms of slow recovery of cardiac excitability and rate-dependent activation failure were studied in single, enzymatically dissociated guinea pig ventricular myocytes and in computer simulations using a modified version of the Beeler and Reuter model for the ventricular cell. On the basis of our results, we developed a simplified analytical model for recovery of cell excitability during diastole. This model was based on the equations for current distribution in a resistive-capacitive circuit. A critical assumption in the model is that, in the voltage domain of the subthreshold responses, the sodium and calcium inward currents do not play a significant role, and only the two potassium outward currents, the delayed rectifier (IK) and the inward rectifier, are operative. The appropriate parameters needed to numerically solve the analytical model were measured in the guinea pig ventricular myocyte, as well as in the Beeler and Reuter cell. The curves of recovery of excitability and the rate-dependent activation patterns generated by numerical iteration of the analytical model equations closely reproduced the experimental results. Our analysis demonstrates that slow deactivation of the delayed rectifier current determines the observed variations in excitability during diastole, whereas the inward rectifier current determines the amplitude and shape of the subthreshold response. Both currents combined are responsible for the development of Wenckebach periodicities in the ventricular cell. The overall study provides new insight into the ionic mechanisms of rate-dependent conduction block processes and may have important clinical implications as well.
Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule
Authors: Maria D Lalioti, Junhui Zhang, Heather M Volkman, Kristopher T Kahle, Kristin E Hoffmann, Hakan R Toka, Carol Nelson-Williams, David H Ellison, Richard Flavell, Carmen J Booth, Yin Lu, David S Geller, Richard P Lifton
Journal: Nature Genetics (2006)
THE RENAL EXCRETION OF ENDOGENOUS CREATININE IN MAN. COMPARISON WITH EXOGENOUS CREATININE AND INULIN
Authors: Benjamin F. Miller, Alexander W. Winkler
Journal: Journal of Clinical Investigation (1938)

The study of the renal excretion of creatinine has been concerned hitherto largely with exo- genous creatinine because of difficulties in the determination of endogenous plasma creatinine.Behre and Benedict (1) and others (2, 3) have denied the presence of any appreciable amount of creatinine in normal plasma.On the other hand several authors have reached the opposite conclusion (4, 5, 6).To avoid this controversy investi- gators of the renal excretion of creatinine have administered creatinine orally or intravenously to raise the concentration in plasma to levels much above that of the " endogenous chromogenic substance."'In this way it is possible to obtain values for exogenous creatinine which are not appreciably influenced by the color development of the endogenous Jaffe-reactive material.This technique was employed by Rehberg (7) when he suggested the creatinine clearance as a measure of the true glomerular filtrate in the human kidney.He gives by mouth 5 grams of creatinine one hour before the test.The Rehberg technique has been so widely employed in physiological and clinical studies that it has become universally known as simply the "creatinine" rather than the " exo- genous creatinine " clearance.Recently it has been demonstrated that, in the dog, this exogenous clearance is equivalent to the inulin clearance (8, 9) and to the ferrocyanide clearance (10).These results make it highly probable that the exogenous creatinine clearance does truly measure the glomerular filtrate in the dog.However, in man, no two of these clear- ances are identical.Miller and Winkler (11) studied the excretion of ferrocyanide in man and 1The terms "chromogenic substance," "Jaffe-reactive material," "apparent creatinine " are all synonymous and indicate the creatinine equivalent of the color produced by the interaction between alkaline picrate and blood filtrates.31
Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions
Authors: Naomi Schlesinger, Rieke E Alten, Thomas Bardin, H Ralph Schumacher, Mark Bloch, Alberto Gimona, Gerhard Krammer, Valda Murphy, Dominik Richard, Alexander K So
Journal: Annals of the Rheumatic Diseases (2012)

Objectives Gouty arthritis patients for whom non-steroidal anti-inflammatory drugs and colchicine are inappropriate have limited treatment options. Canakinumab, an anti-interleukin-1β monoclonal antibody, may be an option for such patients. The authors assessed the efficacy/safety of one dose of canakinumab 150 mg (n=230) or triamcinolone acetonide (TA) 40 mg (n=226) at baseline and upon a new flare in frequently flaring patients contraindicated for, intolerant of, or unresponsive to non-steroidal anti-inflammatory drugs and/or colchicine. Core study co-primary endpoints were pain intensity 72 h postdose (0–100 mm visual analogue scale and time to first new flare. Methods Two 12-week randomised, multicentre, active-controlled, double-blind, parallel-group core studies with double-blind 12-week extensions (response in acute flare and in prevention of episodes of re-flare in gout (β-RELIEVED and β-RELIEVED-II)). Results 82.6% patients had comorbidities. Mean 72-h visual analogue scale pain score was lower with canakinumab (25.0 mm vs 35.7 mm; difference, −10.7 mm; 95% CI −15.4 to −6.0; p&lt;0.0001), with significantly less physician-assessed tenderness and swelling (ORs=2.16 and 2.74; both p≤0.01) versus TA. Canakinumab significantly delayed time to first new flare, reduced the risk of new flares by 62% versus TA (HR: 0.38; 95% CI 0.26 to 0.57) in the core studies and by 56% (HR: 0.44; 95% CI 0.32 to 0.60; both p≤0.0001) over the entire 24-week period, and decreased median C-reactive protein levels (p≤0.0001 at 72 h and 7 days). Over the 24-week period, adverse events were reported in 66.2% (canakinumab) and 52.8% (TA) and serious adverse events were reported in 8.0% (canakinumab) and 3.5% (TA) of patients. Adverse events reported more frequently with canakinumab included infections, low neutrophil count and low platelet count. Conclusion Canakinumab provided significant pain and inflammation relief and reduced the risk of new flares in these patients with acute gouty arthritis.
CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin
Authors: Vanja Karamatic Crew, Nicholas Burton, Alexander Kagan, Carole A. Green, Cyril Levene, Frances Flinter, R. Leo Brady, Geoff Daniels, David J. Anstee
Journal: Blood (2004)
Genome-Wide Selection on Codon Usage at the Population Level in the Fungal Model Organism Neurospora crassa
Authors: C. A. Whittle, Y. Sun, H. Johannesson
Journal: Molecular Biology and Evolution (2012)

Many organisms exhibit biased codon usage in their genome, including the fungal model organism Neurospora crassa. The preferential use of subset of synonymous codons (optimal codons) at the macroevolutionary level is believed to result from a history of selection to promote translational efficiency. At present, few data are available about selection on optimal codons at the microevolutionary scale, that is, at the population level. Herein, we conducted a large-scale assessment of codon mutations at biallelic sites, spanning more than 5,100 genes, in 2 distinct populations of N. crassa: the Caribbean and Louisiana populations. Based on analysis of the frequency spectra of synonymous codon mutations at biallelic sites, we found that derived (nonancestral) optimal codon mutations segregate at a higher frequency than derived nonoptimal codon mutations in each population; this is consistent with natural selection favoring optimal codons. We also report that optimal codon variants were less frequent in longer genes and that the fixation of optimal codons was reduced in rapidly evolving long genes/proteins, trends suggestive of genetic hitchhiking (Hill-Robertson) altering codon usage variation. Notably, nonsynonymous codon mutations segregated at a lower frequency than synonymous nonoptimal codon mutations (which impair translational efficiency) in each N. crassa population, suggesting that changes in protein composition are more detrimental to fitness than mutations altering translation. Overall, the present data demonstrate that selection, and partly genetic interference, shapes codon variation across the genome in N. crassa populations.
Etanercept Treatment in Children With New-Onset Type 1 Diabetes
Authors: Lucy Mastrandrea, Jihnhee Yu, Torsten Behrens, John Buchlis, Christine Albini, Shannon Fourtner, Teresa Quattrin
Journal: Diabetes Care (2009)

OBJECTIVE To gather preliminary data on the feasibility and efficacy of etanercept therapy to prolong endogenous insulin production in pediatric patients with newly diagnosed type 1 diabetes. RESEARCH DESIGN AND METHODS This was a 24-week double-blind, randomized, placebo-controlled study conducted at the Diabetes Center, Women and Children's Hospital of Buffalo. Eighteen subjects (11 male and 7 female, aged 7.8–18.2 years) were randomly assigned to receive either placebo or etanercept. Inclusion criteria included age 3–18 years, GAD-65 and/or islet cell antibody positivity, A1C &amp;gt;6%, three insulin injections per day, white blood cell count 3,000–10,000, platelets &amp;gt;100,000, and normal liver and renal function. Intention-to-treat analysis was used. RESULTS A1C at week 24 was lower in the etanercept group (5.91 ± 0.5%) compared with that in the placebo group (6.98 ± 1.2%; P &amp;lt; 0.05) with a higher percent decrease from baseline than in the placebo group (etanercept 0.41 ± 0.1 vs. placebo 0.18 ± 0.21; P &amp;lt; 0.01). The percent change in C-peptide area under the curve from baseline to week 24 showed a 39% increase in the etanercept group and a 20% decrease in the placebo group (P &amp;lt; 0.05). From baseline to week 24 insulin dose decreased 18% in the etanercept group compared with a 23% increase in the placebo group (P &amp;lt; 0.05). Seventeen patients completed the study, and none withdrew because of adverse events. CONCLUSIONS In this small pilot study, treatment of pediatric patients newly diagnosed with type 1 diabetes with etanercept resulted in lower A1C and increased endogenous insulin production, suggesting preservation of β-cell function. A larger study is needed to further explore safety and efficacy.
Increased oxidative stress and apoptosis susceptibility in peripheral blood mononuclear cells from aspirin sensitive asthmatics in comparison to aspirin tolerant asthmatics and healthy volunteers
Authors: Dorota Kacprzak, Joanna Wieczfinska, Ewa Pniewska, Rafal Pawliczak
Journal: European Respiratory Journal (2014)

Background:  Up to twenty percent of adult asthmatics with nasal polyps are sensitive to aspirin and no unambiguous theory exists which provides a satisfactory explanation for the occurrence of aspirin-induced asthma (AIA) in some asthmatic patients.   Aim:  The main aim of this study was to recognize possible gene targets involved in the pathogenesis of aspirin-induced asthma in Polish population.   Methods:  Peripheral blood mononuclear cells (PBMCs) were separated from blood of three groups of subjects - aspirin sensitive asthmatics (ASA), aspirin tolerant asthmatics (ATA) and healthy volunteers (HV) and then stimulated by either lysine aspirin or lysine as a endogenous control. Next, RNA was isolated, transcribed into cDNA and subjected to qPCR (11 ASA, 7 ATA and 15 HV) studies. Simultaneously, protein was extracted from PBMCs and used in further Western Blot analysis (6 ASA, 6 ATA and 7 HV).   Results:  The analysis of results has shown six genes, which expression at mRNA level was significantly altered between two comprising groups:  FOSL1, PARVG, CNPY3, CSF1, MARVELD1, ERAS . At protein level the change in expression of one protein - FOSL1 was confirmed.   Conclusion:  The ontology analysis shows that a common denominator of most our results is higher oxidative stress and apoptosis susceptibility of AIA than in ATA and healthy controls. Moreover, we observed the lack of peripheral immunogenic processes in the occurrence of hypersensitivity after ingestion of aspirin.   Research funded The Polish National Science Centre no 2011/01/N/NZ5/00334 .
FAMILY CARE, A COMMUNITY RESOURCE IN THE REHABILITATION OF MENTAL PATIENTS
Authors: HANS B. MOLHOLM, WALTER E. BARTON
Journal: American Journal of Psychiatry (1941)

A study is reported of 299 cases placed in family care by the Worcester State Hospital during the 5-year period from 1934 to 1938. This period was selected as it represented the time during which special emphasis was being placed on the use of family care for convalescent cases. Of these cases 23.4% were placed in family care because their family refused to accept them at home; 46.7% had family problems that made it seem advisable to introduce family care as an intermediate step before considering their return to their own homes; 24.2% had no other place to go; and 9.9% were placed in family care for other reasons. The study indicates that: 1. The majority of patients sent into family care (65%) had been hospitalized less than two years prior to placement as contrasted with Copp's group in which 65% had been hospitalized more than two years (5). Convalescent rather than chronic cases are boarded out by us. 2. Forty-two per cent of the patients placed were discharged or paroled and an additional 22% remained in the community in family care. 3. Discharge and visit rates were higher and fewer patients returned to the hospital or remained in family care when patients were placed before the end of the first year of hospital residence. 4. The factors outside the patient which seem to be important in effecting a favorable result in addition to the minimum standards of a comfortable boarding home are: (a) the interest of the caretaker in patient's problems, (b) the opportunity for work and recreation. 5. Family care appears to be a valuable community resource for the rehabilitation of mental patients who do not have a suitable home of their own. This practice deserves more widespread use.
Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute
Authors: C D Johnson
Journal: Gut (2001)

<h3>BACKGROUND</h3> Platelet activating factor (PAF) is believed to amplify the activity of key mediators of the systemic inflammatory response syndrome (SIRS) in acute pancreatitis, resulting in multiorgan dysfunction syndrome. We tested the hypothesis that a potent PAF antagonist, lexipafant, could dampen SIRS and reduce organ failure in severe acute pancreatitis. <h3>METHODS</h3> We conducted a randomised, double blind, placebo controlled, multicentre trial of lexipafant (100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms) involving 290 patients with an APACHE II score &gt;6. Power calculations assumed that complications would be reduced from 40% to 24%. Secondary end points studied included severity of organ failure, markers of the inflammatory response, and mortality rate. <h3>FINDINGS</h3> Overall, 80/138 (58%) patients in the placebo group and 85/148 (57%) in the lexipafant group developed one or more organ failures. The primary hypothesis was invalidated by the unexpected finding that 44% of patients had organ failure on entry into the study; only 39 (14%) developed new organ failure. Organ failure scores were reduced in the lexipafant group only on day 3: median change −1 (range −4 to +8) versus 0 (−4 to +10) in the placebo group (p=0.04). Systemic sepsis affected fewer patients in the lexipafant group (13/138<i>v</i> 4/148; p=0.023). Local complications occurred in 41/138 (30%) patients in the placebo group and in 30/148 (20%) in the lexipafant group (20%; p=0.065); pseudocysts developed in 19 (14%) and eight (5%) patients, respectively (p=0.025). Deaths attributable to acute pancreatitis were not significantly different. Interleukin 8, a marker of neutrophil activation, and E-selectin, a marker of endothelial damage, decreased more rapidly in the lexipafant group (both p&lt;0.05); however, absolute values were not different between the two groups. <h3>INTERPRETATION</h3> The high incidence of organ failure within 72 hours of the onset of symptoms undermined the primary hypothesis, and power calculations for future studies in severe acute pancreatitis will need to allow for this. Lexipafant had no effect on new organ failure during treatment. This adequately powered study has shown that antagonism of PAF activity on its own is not sufficient to ameliorate SIRS in severe acute pancreatitis
A thyroxine-containing peptide can induce murine experimental autoimmune thyroiditis.
Authors: P R Hutchings, A Cooke, K Dawe, B R Champion, M Geysen, R Valerio, I M Roitt
Journal: The Journal of Experimental Medicine (1992)

A synthetic peptide based on a sequence containing thyroxine at position 2553 in thyroglobulin (Tg), and already shown to be recognized by two clonotypically distinct murine Tg autoreactive T cell hybridomas, can trigger primed lymph node cells to transfer thyroiditis to naive recipients. Donor lymph node cells could be prepared from mice immunized either with intact mouse Tg or with this peptide itself. After a second exposure to the priming antigen in vitro, both these populations induced 100% thyroiditis in recipient animals. The importance of the T4 residue in the development of disease was demonstrated by the failure of Tg tryptic peptides depleted of T4 to stimulate pathogenic effectors in vitro, even when the lymph node cells had been taken from mice primed with whole Tg. We conclude that this T4-containing 12mer sequence is a major thyroiditogenic epitope in CBA/J mice although we cannot exclude the possibility that there are other pathogenic epitopes present in the whole Tg molecule.