tbuckley/cabot-search huggingface dataset:
Intrahepatic hepatitis C virus-specific cytotoxic T lymphocyte activity and response to interferon alfa therapy in chronic hepatitis C
Authors: David R. Nelson, Constantine G. Marousis, Tomoyoshi Ohno, Gary L. Davis, Johnson Y.N. Lau
Journal: Hepatology (1998)

Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) have been shown to play a role in host defense and pathogenesis of chronic HCV infection. Our aim was to test the hypothesis that intrahepatic HCV-specific CTL activity may impact subsequent response to interferon alfa (IFN-α) therapy. Of the 37 patients that we have prospectively evaluated for HCV-specific CTL activity in liver, 21 received IFN therapy, and 19 completed a 6-month course and attended 6 to 18 months of follow-up. Intrahepatic CD8 + cells were isolated from liver biopsy tissue and tested against target cells expressing HCV antigens to determine intrahepatic CTL activity. The relationship between treatment response and HCV-specific CTL activity and other factors known to associate with response (genotype, viremia, histology) was analyzed. HCV-specific CTL activity was detected in 9 of 21 patients (and 9 of 19 who completed therapy). After 6 months of IFN therapy, 8 of 19 (42%) patients had normal serum alanine transaminase (ALT) (complete responders). After 18 months of follow-up, only 3 patients (16%) had a sustained biochemical response. Of the 9 patients with detectable HCV-specific CTL activity in their liver before treatment, 7 (78%) developed a complete response. In contrast, only 1 of the 10 patients with no detectable HCV-specific CTL activity developed a complete response to IFN ( P &lt; .01). In 6 of 8 patients with a complete response, including the 3 sustained responders, the CTL response appeared to be directed predominately to the HCV core region. These data suggest that the host immune response, particularly that mediated by CD8 + CTL, may be important in determining the outcome of IFN therapy for chronic HCV infection. Further understanding of the mechanism of action of IFN should impact the design of better therapeutic strategies against chronic HCV infection.
Giant platelet disorder in a patient with type 2B von Willebrand's disease
Authors: Stephan Moll, Alicia Rico Lazarowski, Gilbert C. White
Journal: American Journal of Hematology (1998)

While patients with type 2B von Willebrand's disease often exhibit thrombocytopenia, platelet morphology is typically normal. We describe a 44-year-old Jamaican man with thrombocytopenia and a history of bleeding, who had giant platelets on his peripheral blood film. Functional studies and von Willebrand factor gene sequencing showed him to have type 2B von Willebrand's disease with a heterozygous point mutation resulting in a V553M (V1316M in the new von Willebrand factor gene mutation nomenclature) amino acid substitution. Family studies showed one of his two sisters to have an ill-defined giant-platelet-syndrome with mild thrombocytopenia, but not von Willebrand's disease, indicating that the association of giant platelets and von Willebrand's disease in our patient was most likely coincidental. This report describes the rare concurrence of two uncommon disorders. It also demonstrates how the thrombocytopenia of type 2B von Willebrand's disease can be misdiagnosed as ITP, leading to unnecessary and potentially harmful therapeutic interventions.
Prognostic Value of Different Metabolic Measurements with Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography in Resectable Non-Small Cell Lung Cancer: A Two-Center Study
Authors: Wouter K. de Jong, Henricus F.M. van der Heijden, Jan Pruim, Otilia Dalesio, Wim J.G. Oyen, Harry J.M. Groen
Journal: Journal of Thoracic Oncology (2007)
Abstract 2546: Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with <i>TERT</i> expression.
Authors: Zsofia Kote-Jarai, Edward Saunders, Daniel Leongamornlert, Malgorzata Tymrakiewicz, Tokhir Dadaev, Sarah Jugurnauth, Sara Benlloch, Ali Amin Al Olama, Helen Ross-Adams, David Neal, Rosalind Eeles
Journal: Cancer Research (2013)

Abstract We have previously reported an association between prostate cancer (PrCa) risk and rs2242652 on 5p15. rs2242652 lies in intron 4 of TERT, which encodes telomerase reverse transcriptase, the catalytic subunit of the telomerase ribonucleoprotein complex. Telomerase catalyzes the de novo addition of telomere repeat sequences on to chromosome ends and thereby counterbalances telomere-dependent replicative senescence. Associations between SNPs in the TERT region and multiple cancer types have been reported; however no correlation has been observed thus far between the cancer-associated SNPs in TERT and gene expression or telomere length. To comprehensively evaluate the association between genetic variation across this region and PrCa we performed a fine-mapping analysis by direct genotyping using either a custom Illumina iSelect array (114 SNPs on iCOGS) or Sequenom MassArray iPlex (25 SNPs) followed by imputation of 1,094 SNPs in 22,301 PrCa cases and 22,320 controls in the PRACTICAL consortium. To determine independently associated variants in this region, we performed multiple stepwise logistic regression analysis; SNPs were included in the model if they were significant at P&amp;lt;10−4 after adjustment for other SNPs. Regression models identified multiple independent associations, reflecting the complexity of this region. These SNPs fall into four regions consisting of clusters of highly or moderately correlated variants, and there is only weak LD between SNPs in different regions. To investigate whether SNPs in any of these regions were associated with TERT gene expression, we performed qPCR assays on RNA from benign prostate tissue samples using the Fluidigm Biomark™ HD system. We found evidence that the risk reducing alleles of several variants in region one associated with elevated TERT expression, providing a plausible mechanism for the differential effect of SNPs on PrCa risk. Deep re-sequencing of these loci may help to further refine this region and facilitate selection of prospective causal variants for functional validation studies. Citation Format: Zsofia Kote-Jarai, Edward Saunders, Daniel Leongamornlert, Malgorzata Tymrakiewicz, Tokhir Dadaev, Sarah Jugurnauth, Sara Benlloch, Ali Amin Al Olama, Helen Ross-Adams, David Neal, The UKGPCS Collaborators and The PRACTICAL Consortium, Douglas Easton, Rosalind Eeles. Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2546. doi:10.1158/1538-7445.AM2013-2546
Hospital admission for acute pancreatitis in an English population, 1963-98: database study of incidence and mortality
Authors: Michael J Goldacre, Stephen E Roberts
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objectives</b> To investigate trends in the incidence of acute pancreatitis resulting in admission to hospital, and mortality after admission, from 1963 to 1998. <b>Design</b> Analysis of hospital inpatient statistics for acute pancreatitis, linked to data from death certificates. <b>Setting</b> Southern England. <b>Subjects</b> 5312 people admitted to hospital with acute pancreatitis. <b>Main outcome measures</b> Incidence rates for admission to hospital, case fatality rates at 0-29 and 30-364 days after admission, and standardised mortality ratios at monthly intervals up to one year after admission. <b>Results</b> The incidence of acute pancreatitis with admission to hospital increased from 1963-98: age standardised incidence rates were 4.9 per 100 000 population in 1963-74, 7.7 in 1975-86, and 9.8 in 1987-98. Age standardised case fatality rates within 30 days of admission were 14.2% in 1963-74, 7.6% in 1975-86, and 6.7% in 1987-98. From 1975-98, standardised mortality ratios at 30 days were 30 in men and 31 in women (compared with the general population of equivalent age in the same period = 1), and they remained significantly increased until month 5 for men and month 6 for women. <b>Conclusions</b> Incidence rates for acute pancreatitis with admission to hospital rose in both men and women from 1963 to 1998, particularly among younger age groups. This probably reflects, at least in part, an increase in alcoholic pancreatitis. Mortality after admission has not declined since the 1970s. This presumably reflects the fact that no major innovations in the treatment of acute pancreatitis have been introduced. Pancreatitis remains a disease with a poor prognosis during the acute phase.
AAV1 Mediated Co-expression of Formylglycine-Generating Enzyme and Arylsulfatase A Efficiently Corrects Sulfatide Storage in a Mouse Model of Metachromatic Leukodystrophy
Authors: Toshiyuki Kurai, Sanae Hisayasu, Ryo Kitagawa, Makoto Migita, Hidenori Suzuki, Yukihiko Hirai, Takashi Shimada
Journal: Molecular Therapy (2006)

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by a deficiency of arylsulfatase A (ASA) and is characterized by deposition of sulfatide in all organs, particularly the nervous system. Recently, formylglycine-generating enzyme (FGE) was found to be essential for activation of sulfatases. This study examined the utility of FGE co-expression in AAV type 1 vector (AAV1)-mediated gene therapy of ASA knockout (MLD) mice. AAV1-ASA alone or AAV1-ASA and AAV1-FGE were co-injected into a single site of the hippocampus. Enzyme assay and immunohistochemical analysis showed that ASA was detected not only in the injected hemisphere but also in the non-injected hemisphere by 7 months after injection. Level of ASA activity and extent of ASA distribution were significantly enhanced by co-introduction of AAV1-FGE. Marked reductions in sulfatide levels were observed throughout the entire brain. The unexpectedly widespread distribution of ASA may be due to a combination of diffusion in extracellular spaces, transport through axons, and circulation in cerebrospinal fluid. The rotarod test revealed improvement of neurological functions. These results demonstrate that direct injection of AAV1 vectors expressing ASA and FGE represents a highly promising approach with significant implications for the development of clinical protocols for MLD gene therapy.
Expression of terminal α2-6–linked sialic acid on von Willebrand factor specifically enhances proteolysis by ADAMTS13
Authors: Rachel T. McGrath, Thomas A. J. McKinnon, Barry Byrne, Richard O'Kennedy, Virginie Terraube, Emily McRae, Roger J. S. Preston, Mike A. Laffan, James S. O'Donnell
Journal: Blood (2009)
Pressure-flow Studies in Man During Pulsus Alternans
Authors: R. J. Bache, J. Ruskin, A. Harley, J. C. Greenfield
Journal: Cardiovascular Research (1969)

Phasic aortic blood flow and left ventricular pressure were measured at constant heart rates during pulsus alternans in four patients. Duration of ejection and peak flow rate varied directly with stroke volume, while the pre-ejection period varied inversely. A higher left ventricular end-diastolic pressure preceded large beats in two patients, suggesting alternations of left ventricular filling contributed to pulsus alternans, but was not seen in two others.
Vagal Reaction to Physical Fitness Test
Authors: Alan R. Bures
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The letter by Z. Schlesinger (226:1119,1973) draws the following comment. Postexertional hypotension itself (without sinus arrest) is relatively common in patients asked to stand or sit in the postexercise period, especially in "deconditioned" patients. Because of its frequency and other technical reasons, I have recorded postexercise records in the<i>recumbent</i>position. Since doing this, I have seen no cases of syncope in "healthy" individuals in approximately 1,000 submaximal tests (90% of age-predicted heart rate). The described postexercise period of hypotension and bradycardia, although probably vagal in origin, does not necessarily speak for a normal cardiovascular system in spite of the patient's apparent "health." Postexertional symptoms similar to these are not uncommon in individuals with increased impedance to left ventricular ejection (as in muscular subaortic or valvular aortic stenosis). Muscular subaortic stenosis is often missed. Also, it is quite possible that a similar reaction could be due to
Immunosuppression reactivates viral replication long after resolution of woodchuck hepatitis virus infection
Authors: Stephan Menne, Paul J. Cote, Scott D. Butler, Ilia A. Toshkov, John L. Gerin, Bud C. Tennant
Journal: Hepatology (2007)

Abstract Resolution of hepatitis B virus (HBV) infection is characterized by coordinated humoral and cellular immune responses. Immunity is durable over decades, protecting the host from reinfection and potential activation of residual HBV. Woodchucks infected at birth with woodchuck hepatitis virus (WHV) cleared viremia and developed antibodies to surface antigen (anti-WHs). Woodchucks became seronegative for anti-WHs 3-6 years later, but in some, WHV DNA was detected in serum, liver, and/or peripheral blood mononuclear cells (PBMCs). Those with WHV DNA had increased in vitro cellular immune responses to viral antigens, CD4 and CD8 markers, and Th1-type cytokines, suggesting active WHV-specific T lymphocytes. Immunosuppression for 12 weeks using cyclosporine A in such woodchucks resulted in transient reactivation of WHV replication. Serum of 1 woodchuck that became positive for WHV DNA during immunosuppression was inoculated into WHV-susceptible woodchucks, and a productive infection was demonstrated. The results indicate that after infection durable cellular immunity to WHV is essential for the long-term control of viral replication and is probably maintained by continuous priming from residual virus. Conclusion: These experimental observations demonstrate the potential of immunosuppression to reactivate HBV after resolution of infection. (Hepatology 2007;45:614–622.)
Neonatal Narcotic Addiction
Authors: Carl Zelson, Sook Ja Lee, Marie Casalino
Journal: New England Journal of Medicine (1973)

During an 18-month period (July 1, 1971, to December 31, 1972) 91 infants were born at Metropolitan Hospital to drug-addicted mothers, of whom 46 were methadone addicts and 45 were heroin addicts. In comparing the infants born to 46 methadone-addicted mothers with those born to 45 heroin-addicted mothers, we found that the withdrawal syndrome occurred with equal frequency in both groups, but that the signs of withdrawal and the severity of these signs were greater among the methadone-exposed infants. Also, convulsive seizures and severe hyperbilirubinemia occurred more frequently among the methadone infants. Hyaline-membrane disease, not described among the heroin-exposed newborn infants, was seen in two of the methadone-exposed infants. (N Engl J Med 289:1216–1220, 1973)
Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis
Authors: Kazue Yoshida, Akiharu Kubo, Harumi Fujita, Mariko Yokouchi, Ken Ishii, Hiroshi Kawasaki, Toshifumi Nomura, Hiroshi Shimizu, Keisuke Kouyama, Tamotsu Ebihara, Keisuke Nagao, Masayuki Amagai
Journal: Journal of Allergy and Clinical Immunology (2014)
A novel dipstick developed for rapid Bet V 1‐specific IgE detection: recombinant allergen immobilized via a monoclonal antibody to crystalline bacterial cell‐surface layers
Authors: A. Breitwieser, C. Mader, I. Schocher, K. Hoffmann‐Sommergruber, W. Aberer, O. Scheiner, U. B. Sleytr, M. Sára
Journal: Allergy (1998)

The incidence of allergy to airborne proteins derived from tree and grass pollen, feces of mites, spores of molds, and pet dander has been increasing over the last decades. Since precise diagnosis is a prerequisite for successful immunotherapy, there is a rising demand for rapid, reliable, and inexpensive screening methods such as dipstick assays. With the purified recombinant major birch‐pollen allergen rBet v la as model protein, crystalline bacterial cell‐surface layers (S‐layers) were tested for their applicability as an immobilization matrix for dipstick development. For this purpose, S‐layers were deposited on a mechanically stable microporous support, eross‐linked with glutaraldehyde, and free carboxylic acid groups of the S‐layer protein were activated with carbodiimide. In the present test system, rBet v la was immobilized via the monoclonal mouse antibody BIP 1, which, unlike the allergen, is too large to enter the pores of the S‐layer lattice, and which therefore formed a closed monolayer on the outermost surface of the crystal lattice. Moreover, BIP 1 is known to modulate IgE binding to the allergen. After incubation of the dipsticks in serum, washing of the reaction zone under tap water, and binding of an anti‐IgE alkaline phosphatase conjugate, 5‐bromo‐4‐chloro‐3‐indolyl phosphate/nitro blue tetrazolium was used as substrate, forming an IgE concentration‐dependent colored precipitate on the S‐layer surface. The investigation of patient sera previously tested with the CAP™ system confirmed the specificity of the S‐layer‐based dipstick assay. Since the dipstick is easy to handle and the whole test procedure takes only 90 min, this test system should be applicable for rapid determination of specific IgE and for first screening in the doctor's practice.
Distinct Differences Between Cluster 3 and 4 of Non-IgE Mediated Gastrointestinal Allergy in Allergen-Specific Lymphocyte Proliferation Test and Histological Findings of the GI Mucosa
Authors: Ichiro Nomura, Hideaki Morita, Tetsuo Shoda, Kumiko Morita, Akio Matsuda, HIrotaka Shimizu, Katsuhiro Arai, Atsuko Nakazawa, Yukihiro Ohya, Hirohisa Saito, Kenji Matsumoto
Journal: Journal of Allergy and Clinical Immunology (2013)
Can Routine Commercial Cord Blood Banking Be Scientifically and Ethically Justified?
Authors: Nicholas M Fisk, Irene A. G Roberts, Roger Markwald, Vladimir Mironov
Journal: PLoS Medicine (2005)

Umbilical cord blood--the blood that remains in the placenta after birth--can be collected and stored frozen for years. A well-accepted use of cord blood is as an alternative to bone marrow as a source of hematopoietic stem cells for allogeneic transplantation to siblings or to unrelated recipients; women can donate cord blood for unrelated recipients to public banks. However, private banks are now open that offer expectant parents the option to pay a fee for the chance to store cord blood for possible future use by that same child (autologous transplantation).
Neurogenic histaminergic vasodilation in canine skeletal muscle: mediation by alpha 2-adrenoceptor stimulation.
Authors: B Camazine, R P Shannon, J L Guerrero, R M Graham, W J Powell
Journal: Circulation Research (1988)

This study examines the neurogenic effect of alpha 2-adrenoceptor stimulation on skeletal muscle vascular resistance and its relation to the level of background sympathetic activity. The isolated, separately perfused, neurally intact canine gracilis muscle preparation was used since it permits deliberate and quantifiable alterations in background sympathetic activity, as measured by skeletal muscle vascular resistance. Systemic intravenous UK-14304, a highly selective alpha 2-adrenoceptor agonist, produced a precipitous, neurogenic vasodilation that lowered vascular resistance below the subsequently denervated resistance, thus indicating that an active vasodilation was involved. The overall magnitude of the vasodilation was much greater in animals that had been hemorrhaged to elevate background sympathetic activity than in animals that had been transfused to lower background activity. The neurogenic vasodilation was unaffected by baroreceptor and cardiopulmonary receptor denervation and by prior cholinergic-receptor blockade of the gracilis muscle. Prior H1- and H2-histaminergic-receptor blockade, on the other hand, eliminated the active vasodilation but not a vasodilation down to the subsequently denervated resistance. Prior alpha 1-adrenoceptor blockade lowered resistance down to the subsequently denervated resistance and greatly attenuated the active vasodilation. The present study demonstrates that withdrawal of sympathetic activity by alpha 2-adrenoceptor stimulation produces an active vasodilation resulting from histamine release in skeletal muscle as well as a passive vasodilation resulting from lysis of peripheral vasoconstrictor tone.
Exposure to an obesity-inducing diet early affects the pattern of expression of peroxisome proliferator, retinoic acid, and triiodothyronine nuclear receptors in the rat
Authors: Anabelle Redonnet, Rachel Groubet, Catherine No[euml ]l-Suberville, St[eacute]phane Bonilla, Alfredo Martinez, Paul Higueret
Journal: Metabolism (2001)
Rigid, Complete Annuloplasty Rings Increase Anterior Mitral Leaflet Strains in the Normal Beating Ovine Heart
Authors: Wolfgang Bothe, Ellen Kuhl, John-Peder Escobar Kvitting, Manuel K. Rausch, Serdar Göktepe, Julia C. Swanson, Saideh Farahmandnia, Neil B. Ingels, D. Craig Miller
Journal: Circulation (2011)

Annuloplasty ring or band implantation during surgical mitral valve repair perturbs mitral annular dimensions, dynamics, and shape, which have been associated with changes in anterior mitral leaflet (AML) strain patterns and suboptimal long-term repair durability. We hypothesized that rigid rings with nonphysiological three-dimensional shapes, but not saddle-shaped rigid rings or flexible bands, increase AML strains.Sheep had 23 radiopaque markers inserted: 7 along the anterior mitral annulus and 16 equally spaced on the AML. True-sized Cosgrove-Edwards flexible, partial band (n=12), rigid, complete St Jude Medical rigid saddle-shaped (n=12), Carpentier-Edwards Physio (n=12), Edwards IMR ETlogix (n=11), and Edwards GeoForm (n=12) annuloplasty rings were implanted in a releasable fashion. Under acute open-chest conditions, 4-dimensional marker coordinates were obtained using biplane videofluoroscopy along with hemodynamic parameters with the ring inserted and after release. Marker coordinates were triangulated, and the largest maximum principal AML strains were determined during isovolumetric relaxation. No relevant changes in hemodynamics occurred. Compared with the respective control state, strains increased significantly with rigid saddle-shaped annuloplasty ring, Carpentier-Edwards Physio, Edwards IMR ETlogix, and Edwards GeoForm (0.14 ± 0.05 versus 0.16 ± 0.05, P=0.024, 0.15 ± 0.03 versus 0.18 ± 0.04, P=0.020, 0.11 ± 0.05 versus 0.14 ± 0.05, P=0.042, and 0.13 ± 0.05 versus 0.16 ± 0.05, P=0.009), but not with Cosgrove-Edwards band (0.15 ± 0.05 versus 0.15 ± 0.04, P=0.973).Regardless of three-dimensional shape, rigid, complete annuloplasty rings, but not a flexible, partial band, increased AML strains in the normal beating ovine heart. Clinical studies are needed to determine whether annuloplasty rings affect AML strains in patients, and, if so, whether ring-induced perturbations in leaflet strain states are linked to repair failure.
Porokeratosis: immunosuppression and exposure to sunlight
Authors: P.L. BENCINI, C. CROSTI, F. SALA
Journal: British Journal of Dermatology (1987)

Journal Article Porokeratosis: immunosuppression and exposure to sunlight Get access P.L. BENCINI, P.L. BENCINI Institute of Clinical Dermatology I and Paediatric Dermatology, University of Milan, Milan, Italy Bencini Pier Luca, M.D., Clinica Dermatologica 1, Via Pace 9, 20122 Milanco, Italy. Search for other works by this author on: Oxford Academic Google Scholar C. CROSTI, C. CROSTI Institute of Clinical Dermatology I and Paediatric Dermatology, University of Milan, Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar F. SALA F. SALA Institute of Clinical Dermatology I and Paediatric Dermatology, University of Milan, Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 116, Issue 1, 1 January 1987, Pages 113–116, https://doi.org/10.1111/j.1365-2133.1987.tb05798.x Published: 01 January 1987