tbuckley/cabot-search huggingface dataset:
1234 A NEWLY MODIFIED HCV REPLICON ASSAY WITH AN EXPANDED CAPABILITY TO EVALUATE THE SUSCEPTIBILITY OF GT1A/B PATIENT VIRUSES TO POLYMERASE INHIBITORS
Authors: D. Han, K. Strammen, M. Cheng, S. Choe, E. Anton, A. Rivera, C.J. Petropoulos, J.D. Reeves
Journal: Journal of Hepatology (2011)
Membrane-bound cytochrome b5 reductase (methemoglobin reductase) in human erythrocytes. Study in normal and methemoglobinemic subjects.
Authors: D Choury, A Leroux, J C Kaplan
Journal: Journal of Clinical Investigation (1981)

In this study we present evidence that in human erythrocytes NADH-cytochrome b5 reductase (methemoglobin reductase) is not only soluble but also tightly bound to the membrane. The membrane methemoglobin reductase-like activity is unmasked by Triton X-100 treatment, and represents about half of the total activity in the erythrocytes. Like the amphiphilic microsomal-bound cytochrome b5 reductase, the erythrocyte membrane-bound enzyme is solubilized by cathepsin D. Because this treatment is effective on unsealed ghosts but not on resealed (inside-in) ghosts, it is concluded that the enzyme is strongly bound to the inner face of the membrane. The erythrocyte membrane enzyme is antigenically similar to the soluble enzyme. The two forms of enzyme are specified by the same gene, in that both were found defective in six patients with recessive congenital methemoglobinemia. We suggest that the cytochrome b5 reductase of the erythrocyte membrane is the primary gene product. A posttranslational partial proteolysis probably gives rise to the soluble form of the enzyme, which serves as a methemoglobin reductase.
Gestational age of recipient determines pattern and level of transgene expression following in utero retroviral gene transfer
Authors: Christopher D. Porada, Paul J. Park, Graça Almeida-Porada, Wansheng Liu, Ferhat Ozturk, Hudson A. Glimp, Esmail D. Zanjani
Journal: Molecular Therapy (2004)

The direct vector injection approach was used in the fetal sheep model of in utero gene therapy to determine the effects of the recipient gestational age on the efficacy and pattern of liver, lung, and brain transduction and transgene expression. The livers contained foci of transgene-expressing hepatocytes and demonstrated an inverse correlation between recipient age and hepatocyte transduction/transgene expression, with higher levels of gene transfer/expression early in gestation and lower levels late in gestation. Conversely, the percentage of transgene-expressing cells within the lungs of these same animals increased with gestational age, with the majority of transduction occurring in epithelium and fibroblasts. In contrast to the lung and liver, transgene-expressing cells within the brain were extremely limited at all gestational ages tested. Our results demonstrate that numerous nonhematopoietic cells within the liver and lung are transduced following direct injection of murine retroviral vectors into fetal sheep and suggest that the developmental stage of each organ at the time of injection may determine its susceptibility to in utero gene transfer and subsequent levels of transgene expression. Our results suggest that with further vector optimization this approach may be useful for treating diseases that involve the lung and liver early in development.
LONG-TERM CLINICAL OUTCOMES AFTER PERCUTANEOUS CORONARY INTERVENTION FOR CHRONIC TOTAL OCCLUSIONS IN PATIENTS WITH AND WITHOUT DIABETES MELLITUS: FIVE-YEAR OUTCOMES FROM A 1,791 PATIENT MULTI-NATIONAL REGISTRY
Authors: Bimmer E. Claessen, Cosmo Godino, Kotaru Obunai, Sunil Kanwal, Mauro Carlino, Young-Hak Kim, Carlo DiMario, Seung-Jung Park, Gregg W. Stone, Antonio Colombo, George D. Dangas, Martin Leon, Jeffrey W. Moses, Roxana Mehran
Journal: Journal of the American College of Cardiology (2011)
Erythrocyte enzyme activities in myelodysplastic syndromes: Elevated pyruvate kinase activity
Authors: Kenzaburo Tani, Hisaichi Fujii, Keisuke Takahashi, Hideki Kodo, Shigetaka Asano, Fumimaro Takaku, Shiro Miwa
Journal: American Journal of Hematology (1989)

The erythrocyte enzyme activities in twenty-six cases of myelodysplastic syndromes were determined. There were remarkably abnormal levels in seven cases; namely, four cases showed increased hexokinase activity, three cases showed increased pyruvate kinase activity, and two cases showed increased adenosine deaminase activity. Among these, one case with elevated pyruvate kinase activity showed the novel expression of M2-type pyruvate kinase activity, in addition to the R-type pyruvate kinase activity normally found in erythrocytes. Southern blotting of peripheral leucocyte DNA revealed only an amplified PK-LR genome, which derived from the chromosomal abnormality of a 1;7 translocation. The mechanism responsible for switching M2-type to R-type during erythroid maturation was considered to be partially disrupted in this case.
Sunlight, Skin Cancer, and Sunscreens
Authors: Lewis H. Kaminester
Journal: JAMA (1975)

THE SOLAR electromagnetic spectrum ranges widely from below the short ultraviolet wavelength through the visible light spectrum and beyond. The ozone in our stratosphere 25 km above the earth effectively protects us from the short-wave, highenergy ultraviolet (UV) light. But UV light that does penetrate the atmosphere contains the erythrogenic spectrum that causes the all-too-familiar sunburn reaction. Redness begins two to eight hours after exposure and usually peaks at 24 hours. When the exposure has been longer than five times the minimum erythema dose (MED) (ie, the amount of energy from a defined light source, like the sun, producing a barely perceptible sunburn or erythema of the skin under stated conditions), blistering, pain, and fever may also occur. Although immediate darkening of pigment may accompany such erythema, due to oxidation of colorless preformed melanin already in the skin, it is transient, fading within a few hours. The socially sought-after, durable
Left ventricular internal resistance and unloaded ejection flow assessed from pressure-flow relations: a flow-clamp study on isolated rabbit hearts.
Authors: S R Vaartjes, H B Boom
Journal: Circulation Research (1987)

Left ventricular pressure-flow relations were studied, using excised working rabbit hearts and imposing constant flow ejections (flow-clamps) to separate the effects of flow on pressure from those of time, flow duration, starting volume, ejected volume, and volume at specified time. Pressure-flow data at given volume and time were independent of flow duration, starting volume, and ejected volume for flow-clamp durations exceeding 30 msec. Flow history independent of pressure-flow relations was linear for flow values larger than +/- 5 ml/sec. The time-varying elastance model, E(t), of the ventricle was extended with a resistive component. Transient effects of flow can be explained by including a second elastance. The resulting verified 3-component model is consistent with recent reported experimental findings. The properties of internal resistance correspond to a constant unloaded ejection flow Qmax, which was tested by extrapolating the linear pressure-flow relations to zero pressure. Qmax reached a plateau value of approximately 25 ml/sec within 50 msec after the start of contraction. In relaxation, Qmax is only slightly smaller. Qmax did not depend on volume; therefore, the following equation was adequate for the relation between pressure, p(t); volume, V(t); and flow Q(t), during the flow-clamped ejections from 30 minutes after the start of the flow: (t) = E(t).(V(t)-Vd).(1-Q(t)/Qmax)
Massive Prolapse of Redundant Bladder Mucosa
Authors: Ponce Bernardo
Journal: JAMA (1963)

PROLAPSE OF THE BLADDER or any of its parts is a rather unusual occurrence and only comparatively few cases have been reported in the world literature. Most text books of urology say only that it occurs and give little more information about the condition. Flocks and Culp,<sup>1</sup>in their most recent edition of<i>Surgical Urology</i>, mention that the condition is rare and that severe cases require surgical repair through the suprapubic route. Prolapse outside the urethra can only occur in females. In 1937, Campbell<sup>2</sup>reported six instances of redundant trigonal mucosa found at autopsy, four of which were in boys. Espinosa and associates<sup>3</sup>reported a case of redundant mucosa from the trigone area which prolapsed through the urethra and presented itself between the vulva in the same manner as in the case which we have observed. Morton et al<sup>4</sup>had a similar case to that of
Trends in Incidence and Prevalence of Major Transfusion-Transmissible Viral Infections in US Blood Donors, 1991 to 1996
Authors: Simone A. Glynn
Journal: JAMA (2000)

ContextEvaluating trends in blood donor infectious disease rates is essential for monitoring blood supply safety and donor screening effectiveness. ObjectiveTo determine changes over time in blood donor population infection rates of human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis C virus (HCV), and hepatitis B virus (HBV).Design Cross-sectional survey data from the National Heart, Lung, and Blood Institutesponsored Retrovirus Epidemiology Donor Study. Setting Five blood centers in different regions of the United StatesParticipants A total of 1.9 million volunteer blood donors with 1 or more nonautologous donations from January 1991 to December 1996. Main Outcome MeasuresChanges in rates of HIV, HTLV, HCV, and HBV infections were evaluated by comparing yearly prevalence estimates (per 100 000 donations) for first-time allogeneic donors and period-specific incidence rates (IRs) (per 100000 person-years) for repeat allogeneic donors between 1991 and 1996 (for HCV, from about March 1992 to June 1996). ResultsPrevalence of HIV decreased in first-time donors from 0.030% to 0.015% (P=.006) and HCV prevalence decreased from 0.63% to 0.40% (PϽ.001).Trends were not statistically significant for the proportion of first-time donors with hepatitis B surface antigen (HBsAg) or HTLV.For repeat donors, IRs did not change significantly, indicating a stable but low level of seroconversion.The overall IRs (95% confidence intervals) per 100 000 person-years were 2.92 (2.26-3.70)for HIV, 1.59 (1.12-2.19)for HTLV, 3.25 (2.36-4.36)for HCV, and an estimated 10. 43 (7.99-13.37)for HBV (based on an HBsAg rate of 2.66 [2.04-3.41]with presumed false-positive results considered negative).The HBV IR estimate with presumed false-positive results considered positive (for comparability to previous analyses) was 17.83 (14.60-21.56). ConclusionThe decrease in HIV and HCV prevalence rates, combined with the previously documented lower rates of infection in first-time donors compared with the general population, suggests the continued benefit of behavioral risk factor screening.
NOTE ON THE BACTERIOLOGICAL QUALITIES OF ROOF-COLLECTED SAMPLES OF RAIN WATER
Authors: A. Houston
Journal: BMJ (1919)

As a result 'of a conference of delegates of municipal authorities and others, held in connexion with the Smoke Abatement Exhibition. in 1912, a committee was formed for the investigation of' atmosplheric pollution..The committee's first report was publislhed in 1916, and together witlh the succeeding reports are full of valu&ble informa- tion bearing directly, or indirectly, on the quality of rain water.Tle writer, in his' recent book on RBural Water Supplies dind their Puriftcation,* dealt fairly exhaustively with rain iwater as a source f water supply.From a health point of view, rain water has the advantage tihat it is practically free from the possibility of humian excremental pollution.That is, of course, excluding those 'cases where' the :-rain water is stored in pervious underground tankss, unfavourably situated as regards drains, 'cesepools, and other .sources of dangerous contamination.Oln the other hand, roof-collected rain water.may be con- taminated by the " droppings " of birds, the exereta of rats.mice, and other lower animals, and a multitude of flies, insects, etc.
ABC of healthy travel. Immunisation-II.
Authors: E Walker, G Williams
Journal: BMJ (1983)

IMMUNISATION -IIOccasionally recommended: rabies Human diploid cell vaccine is effective against rabies and has few side effects.Pre-exposure prophylaxis should be recommended to high risk groups, such as veterinarians working in areas enzootic for rabies. Rabies vaccinePostexposure prophylaxis with human diploid cell vaccine is also Available fram effective.There have, however, been recent reports of two deaths from PHLS Laboratories in Birminghaim, Cardiff, Colindale, probable rabies after multiple dog bites when this vaccine was used.In Exeter, Leeds, Liverpool and Newcastle one case the timing of the course of injections was optimal but in the Hosptal pharmacies in Aberdeen (Royal Infirmary), other there was a two-day delay before the first injection.Neither patient Dundee (King's Cross), Edinburgh (Western General), received rabies immunoglobulin.Despite these first failures, postexposure Glasgow (Ruchill), and Inverness (Raigmore) eevdrbe m uolbl.Dst hsefstalrs,ptxoue
Risk Factors for Myocardial Infarction Associated With the Chicago Snowstorm of Jan 13-15, 1979
Authors: Roger I. Glass
Journal: JAMA (1981)

Sixty male survivors of acute myocardial infarction in the week after the Chicago blizzard of Jan 15, 1979, were matched by hospital and sex with 60 myocardial infarction survivors from a week without snowfall to determine whether a history of previous heart disease or of cardiac risk factors increased the risk of a postblizzard myocardial infarction. Cases did not differ significantly from control subjects with respect to age, percentage working full time, or percentage with a history of heart disease, hypertension, smoking, diabetes mellitus, obesity, or gout. Hypercholesterolemia was four times as common among cases as among controls.
Reduction of colonic motility by intravenous nicardipine in irritable bowel syndrome.
Authors: A Prior, S R Harris, P J Whorwell
Journal: Gut (1987)

The effect of nicardipine, a new dihydropyridine calcium antagonist, on postprandial colonic motility was assessed in 10 patients with irritable bowel syndrome. Each patient was studied twice receiving intravenously either N saline or nicardipine after a 1000 calorie meal. In the control study there was a significant (p less than 0.01) postprandial increase in the contractile activity of the colon, reaching a peak at approximately 20 minutes. Intravenous nicardipine completely abolished the colonic response, with a significant reduction in the number (p less than 0.005) and amplitude (p less than 0.005) of contractions and of the motility index (p less than 0.025). These results support the need for further studies to evaluate the therapeutic role of nicardipine in the irritable bowel syndrome.
Congenital Deficiency of α2-Plasmin Inhibitor Associated with Severe Hemorrhagic Tendency *
Authors: Nobuo Aoki, Hidehiko Saito, Tadashi Kamiya, Katsuo Koie, Yoichi Sakata, Masateru Kobakura
Journal: Journal of Clinical Investigation (1979)

alpha(2)-Plasmin inhibitor (alpha(2)PI) is a recently characterized, fast-reacting plasmin inhibitor in human plasma that appears to play an important role in regulation of in vivo fibrinolysis. We report here a case of complete deficiency of alpha(2)PI in man. The patient, a 25-yr-old Japanese man, had a life-long severe bleeding tendency (hemarthrosis and excessive bleeding after trauma). The following tests were within normal limits: platelet count, bleeding time, thrombin time, prothrombin time, partial thromboplastin time, titers of known clotting factors, platelet glass bead retention, Factor VIII-related antigen, platelet aggregation by ADP, collagen and ristocetin, and clot retraction. Routine liver function tests were also normal. The only abnormal finding was that whole blood clot lysis was extemely rapid and was complete in 4-8 h. The concentration of plasma protease inhibitors, including alpha(2)-macro-globulin, antithrombin III, alpha(1)-antitrypsin, and C1INH, were all normal. The concentration of alpha(2)-PI in the patient's plasma, assayed by immunological methods, was <0.1 mg/100 ml (normal concentration, 6.1+/-0.88 mg/100 ml [mean+/-SE]) and functional assays showed a complete deficiency of alpha(2)PI. Addition of purified alpha(2)PI to the patient's whole blood completely corrected the accelerated fibrinolysis. The patient's parents, four siblings, and four other members of this family were asymptomatic, but the titers of alpha(2)PI in their plasmas were congruent with50% of normal pooled plasma. There were three consanguineous marriages in this family, and the alpha(2)PI deficiency appears to have been inherited as an autosomal recessive trait. We speculate that alpha(2)PI deficiency in this patient has led to uninhibited in vivo fibrinolysis that probably causes the severe hemorrhagic tendency. Thus, this study indicates the important role of alpha(2)PI in hemostasis.
BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer
Authors: Rekha Rai, Hui Dai, Asha S. Multani, Kaiyi Li, Koei Chin, Joe Gray, John P. Lahad, Jiyong Liang, Gordon B. Mills, Funda Meric-Bernstam, Shiaw-Yih Lin
Journal: Cancer Cell (2006)
Research team isolates major non-A, non-B hepatitis virus
Authors: William Golden
Journal: JAMA (1979)

After nearly a decade of searching by many investigators, French hepatologist Christian Trepo, MD, has presented the first photographs of a non-A, non-B hepatitis virion. Reporting at the American Association for the Study of Liver Diseases meeting in Chicago, Trepo also detailed his experiences with specific serological tests for non-A, non-B viral antigens and antibody. On the basis of Trepo's findings, many in the audience expressed the belief that practical screening procedures for non-A, non-B hepatitis in banked blood may soon become a reality, thus controlling this infection that comprises nearly 90% of posttransfusion hepatitis. Since hepatitis A virus rarely, if ever, causes a posttransfusion infection, the development of sensitive screening techniques for hepatitis B virus in the early part of this decade gave hope that transfusionassociated hepatitis would become a rarity. It developed, however, that because of the existence of still another infectious agent, which came to be called
Physical activity at work and duodenal ulcer risk.
Authors: B D Katschinski, R F Logan, M Edmond, M J Langman
Journal: Gut (1991)

<h3>Background</h3> Male infertility is a prevalent issue worldwide, mostly due to the impaired sperm motility. Multiple morphological abnormalities of the sperm flagella (MMAF) present aberrant spermatozoa with absent, short, coiled, bent and irregular-calibre flagella resulting in severely decreased motility. Previous studies reported several MMAF-associated genes accounting for approximately half of MMAF cases. <h3>Methods and result</h3> We conducted genetic analysis using whole-exome sequencing in 88 Han Chinese MMAF probands. <i>CFAP65</i> homozygous mutations were identified in four unrelated consanguineous families, and <i>CFAP65</i> compound heterozygous mutations were found in two unrelated cases with MMAF. All these <i>CFAP65</i> mutations were null, including four frameshift mutations (c.1775delC [p.Pro592Leufs*8], c.3072_3079dup [p.Arg1027Profs*41], c.1946delC [p.Pro649Argfs*5] and c.1580delT [p.Leu527Argfs*31]) and three stop-gain mutations (c.4855C&gt;T [p.Arg1619*], c.5270T&gt;A [p.Leu1757*] and c.5341G&gt;T [p.Glu1781*]). Additionally, two homozygous <i>CFAP65</i> variants likely affecting splicing were identified in two MMAF-affected men of Tunisian and Iranian ancestries, respectively. These biallelic variants of <i>CFAP65</i> were verified by Sanger sequencing and were absent or very rare in large data sets aggregating sequence information from various human populations. <i>CFAP65</i>, encoding the cilia and flagella associated protein 65, is highly and preferentially expressed in the testis. Here we also generated a frameshift mutation in mouse orthologue <i>Cfap65</i> using CRISPR-Cas9 technology. Remarkably, the phenotypes of <i>Cfap65</i>-mutated male mice were consistent with human MMAF. <h3>Conclusions</h3> Our experimental observations performed on both human subjects and on <i>Cfap65</i>-mutated mice demonstrate that the presence of biallelic mutations in <i>CFAP65</i> causes the MMAF phenotype and impairs sperm motility.
Design of a Novel Integration-deficient Lentivector Technology That Incorporates Genetic and Posttranslational Elements to Target Human Dendritic Cells
Authors: Semih U Tareen, Brenna Kelley-Clarke, Christopher J Nicolai, Linda A Cassiano, Lisa T Nelson, Megan M Slough, Chintan D Vin, Jared M Odegard, Derek D Sloan, Neal Van Hoeven, James M Allen, Thomas W Dubensky, Scott H Robbins
Journal: Molecular Therapy (2013)

As sentinels of the immune system, dendritic cells (DCs) play an essential role in regulating cellular immune responses. One of the main challenges of developing DC-targeted therapies includes the delivery of antigen to DCs in order to promote the activation of antigen-specific effector CD8 T cells. With the goal of creating antigen-directed immunotherapeutics that can be safely administered directly to patients, Immune Design has developed a platform of novel integration-deficient lentiviral vectors that target and deliver antigen-encoding nucleic acids to human DCs. This platform, termed ID-VP02, utilizes a novel genetic variant of a Sindbis virus envelope glycoprotein with posttranslational carbohydrate modifications in combination with Vpx, a SIVmac viral accessory protein, to achieve efficient targeting and transduction of human DCs. In addition, ID-VP02 incorporates safety features in its design that include two redundant mechanisms to render ID-VP02 integration-deficient. Here, we describe the characteristics that allow ID-VP02 to specifically transduce human DCs, and the advances that ID-VP02 brings to conventional third-generation lentiviral vector design as well as demonstrate upstream production yields that will enable manufacturing feasibility studies to be conducted.