tbuckley/cabot-search huggingface dataset:
Very Late Relapses in Patients With Burkitt's Lymphoma: Clinical and Serologic Studies
Authors: R J Biggar, F K Nkrumah, W Henle, P H Levine
Journal: JNCI Journal of the National Cancer Institute (1981)

Of 117 patients in remission for at least 12 months after chemotherapy for confirmed Burkitt's lymphoma, 14 subsequently relapsed. Frequency of ever relapsing in this group varied from 12% 2 years after chemotherapy to 3–8% 3–6 years after chemotherapy. Risk of very late relapse (VLR) increased with the occurrence of meningeal disease and/or relapse before a remission of 12 months or more was achieved. The use of combination chemotherapy and especially prophylactic intrathecal methotrexate significantly lowered the risk of VLR (P<0.03). Serial testing for antibodies to Epstein-Barr viral capsid antigen to the diffuse and restricted components of the early antigen complex and to the Epstein-Barr virus-specific nuclear antigen revealed minor fluctuations but no consistent increases in antibody titers preceding detection of VLR. The serologic follow-up tests thus were not clinically useful for prediction of the imminence of a recurrence. Patients developing VLR generally maintained moderate-to-high titers of antibodies to restricted or diffuse components throughout the long remission periods, which indicated that they were not beyond the danger of a relapse at an unspecified time in the future.
Functionally Distinct Subsets of CD1d-restricted Natural Killer T Cells Revealed by CD1d Tetramer Staining
Authors: Jenny E. Gumperz, Sachiko Miyake, Takashi Yamamura, Michael B. Brenner
Journal: The Journal of Experimental Medicine (2002)

CD1d-restricted natural killer (NK)T cells are known to potently secrete T helper (Th)1 and Th2 cytokines and to mediate cytolysis, but it is unclear how these contrasting functional activities are regulated. Using lipid antigen–loaded CD1d tetramers, we have distinguished two subsets of CD1d-restricted T cells in fresh peripheral blood that differ in cytokine production and cytotoxic activation. One subset, which was CD4−, selectively produced the Th1 cytokines interferon γ and tumor necrosis factor α, and expressed NKG2d, a marker associated with cytolysis of microbially infected and neoplastic cells. This subset up-regulated perforin after exposure to interleukin (IL)-2 or IL-12. In contrast, CD4+ CD1d-restricted NKT cells potently produced both Th1 and Th2 cytokines, up-regulated perforin in response to stimulation by phorbol myristate acetate and ionomycin but not IL-2 or IL-12, and could be induced to express CD95L. Further, for both CD1d-restricted NKT cell subsets, we found that antigenic stimulation induced cytokine production but not perforin expression, whereas exposure to inflammatory factors enhanced perforin expression but did not stimulate cytokine production. These results show that the various activities of CD1d-restricted T cells in tumor rejection, autoimmune disease, and microbial infections could result from activation of functionally distinct subsets, and that inflammatory and antigenic stimuli may influence different effector functions.
Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast. Implications for venous injection.
Authors: D M Skyba, A R Jayaweera, N C Goodman, S Ismail, G Camarano, S Kaul
Journal: Circulation (1994)

BACKGROUND The purpose of this study was to determine whether myocardial perfusion can be quantified with myocardial contrast echocardiography using left atrial (LA) injection of contrast. METHODS AND RESULTS Based on a series of in vitro and in vivo experiments, the optimal dose of sonicated albumin microbubbles injected into the LA for establishing a linear relation between video intensity and blood volume in the anterior myocardium was determined. In 10 open-chest dogs, myocardial blood flow (MBF) was augmented by increasing myocardial blood volume (MBV) with an intravenous infusion of phenylephrine HCl. In the presence of this drug, left anterior descending artery stenosis was produced, followed by release of stenosis, to change MBF within the anterior myocardium. MBV was calculated by dividing radiolabeled microsphere-derived MBF by microbubble transit rate. There was close coupling between MBF and MBV in the anterior myocardium during LA injection of contrast (y = 1.0x-0.03, SEE = 1.07, r = .92, P &lt; .001). An excellent correlation was also noted between background-subtracted peak video intensity and MBV (y = 0.24x + 0.73, SEE = 0.36, r = .88, P &lt; .001). On multivariate analysis, background-subtracted peak video intensity correlated best with MBV. CONCLUSIONS Myocardial perfusion can be quantified from time-intensity curves derived from the anterior myocardium after LA injection of contrast. Background-subtracted peak video intensity in this situation correlates closely with MBV. When MBV and MBF are closely coupled, such as during inotropic stimulation of the heart, background-subtracted peak video intensity also correlates closely with MBF. Since there are similarities in the models of LA and venous injections, these data indicate that it may be feasible to quantify myocardial perfusion with myocardial contrast echocardiography after venous injection of contrast.
H-Y antigen. Cell surface mapping and testosterone-induced supramolecular repatterning.
Authors: L Flaherty, D Zimmerman, S S Wachtel
Journal: The Journal of Experimental Medicine (1979)

Previous work with the antibody-blocking technique showed that the map of surface components for thymocytes prefixed with paraformaldehyde is the same as the map for unfixed thymocytes, with the following exception: after exposure to anti-TL or anti-Db, TL and H-2Db occupy adjacent positions on unfixed cells but not on fixed cells. This was interpreted as an indication that activation of particular components of the surface phenotype initiates ordered changes in the display of cell-surface molecules, approximation of TL and Db in this instance. These studies have now been extended to the H-Y component on the surface of male cells. On fixed male mouse thymocytes, H-Y lies adjacent to TL and relatively distant from H-2Db, H-2Kb, H-2Lb, Lyt-1.2, and Lyt-2.2. However, on unfixed male mouse thymocytes, similarly exposed to H-Y antibody, H-Y and H-2Db are adjacent. Presumably, this engagement of H-Y sites by H-Y antibody brings H-Y and H-2Db together. Evidence that this change in pattern may be physiologically relevant comes from the finding that testosterone, but not estradiol, caused the same selective approximation of H-Y and H-2Db.
Comprehensive Analysis of Archaeal tRNA Genes Reveals Rapid Increase of tRNA Introns in the Order Thermoproteales
Authors: Junichi Sugahara, Kaoru Kikuta, Kosuke Fujishima, Nozomu Yachie, Masaru Tomita, Akio Kanai
Journal: Molecular Biology and Evolution (2008)

The analysis of archaeal tRNA genes is becoming more important to evaluate the origin and evolution of tRNA molecule. Even with the recent accumulation of complete genomes of numerous archaeal species, several tRNA genes are still required for a full complement of the codon table. We conducted comprehensive screening of tRNA genes from 47 archaeal genomes by using a combination of different types of tRNA prediction programs and extracted a total of 2,143 reliable tRNA gene candidates including 437 intron-containing tRNA genes, which covered more than 99.9% of the codon tables in Archaea. Previously, the content of intron-containing tRNA genes in Archaea was estimated to be approximately 15% of the whole tRNA genes, and most of the introns were known to be located at canonical positions (nucleotide position between 37 and 38) of precursor tRNA (pre-tRNA). Surprisingly, we observed marked enrichment of tRNA introns in five species of the archaeal order Thermoproteales; about 70% of tRNA gene candidates were found to be intron-containing tRNA genes, half of which contained multiple introns, and the introns were located at various noncanonical positions. Sequence similarity analysis revealed that approximately half of the tRNA introns found at Thermoproteales-specific intron locations were highly conserved among several tRNA genes. Intriguingly, identical tRNA intron sequences were found within different types of tRNA genes that completely lacked exon sequence similarity, suggesting that the tRNA introns in Thermoproteales could have been gained via intron insertion events at a later stage of tRNA evolution. Moreover, although the CCA sequence at the 3′ terminal of pre-tRNA is added by a CCA-adding enzyme after gene transcription in Archaea, most of the tRNA genes containing highly conserved introns already encode the CCA sequence at their 3′ terminal. Based on these results, we propose possible models explaining the rapid increase of tRNA introns as a result of intron insertion events via retrotransposition of pre-tRNAs. The sequences and secondary structures of the tRNA genes and their bulge-helix-bulge motifs were registered in SPLITSdb (http://splits.iab.keio.ac.jp/splitsdb/), a novel and comprehensive database for archaeal tRNA genes.
T-Cell Distribution and Adhesion Receptor Expression in Metastatic Melanoma
Authors: Carsten Weishaupt, Karla N. Munoz, Elizabeth Buzney, Thomas S. Kupper, Robert C. Fuhlbrigge
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Metastatic malignant melanoma is a devastating disease with a poor prognosis. Recent therapeutic trials have focused on immunotherapy to induce development of endogenous antitumor immune responses. To date, such protocols have shown success in activation of tumor-specific CTL but no overall improvement in survival. To kill tumor, antigen-specific CTL must efficiently target and enter tumor tissue. The purpose of this study was to examine the pathway of leukocyte migration to metastatic melanoma. Experimental design: Peripheral blood and metastatic melanoma tissues (n = 65) were evaluated for expression of adhesion molecules using immunohistochemistry of tumor sections and flow cytometry of tumor-associated and peripheral blood CTL and compared with healthy controls. CTL expressing T-cell receptors for the melanoma antigen MART-1 were identified in a subset of samples by reactivity with HLA-A2 tetramers loaded with MART-1 peptide. Results: Results show that the majority of metastatic melanoma samples examined do not express the vascular adhesion receptors E-selectin (CD62E), P-selectin (CD62P), and intercellular adhesion molecule-1 (CD54) on vessels within the tumor boundaries. Strong adhesion receptor expression was noted on vessels within adjacent tissue. Tumor-associated T lymphocytes accumulate preferentially in these adjacent areas and are not enriched for skin- or lymph node–homing receptor phenotype. Conclusion: Expression of leukocyte homing receptors is dysregulated on the vasculature of metastatic melanoma. This results in a block to recruitment of activated tumor-specific CTL to melanoma metastases and is a likely factor limiting the effectiveness of current immunotherapy protocols.
Is Prehypertension a Risk Factor for the Development of Type 2 Diabetes?
Authors: David R. Mullican, Carlos Lorenzo, Steven M. Haffner
Journal: Diabetes Care (2009)

OBJECTIVE Prehypertension is associated with cardiovascular disease and insulin resistance. However, whether subjects with prehypertension have more diabetes risk is not known. We examine whether prehypertension is a risk factor for developing type 2 diabetes. RESEARCH DESIGN AND METHODS Incident diabetes was examined in nondiabetic normotensive participants in the San Antonio Heart Study (n = 2,767; aged 25–65 years; median follow-up 7.8 years). RESULTS Incident diabetes was 12.4% in subjects with prehypertension and 5.6% in subjects with normal blood pressure. The odds of incident diabetes were 2.21 greater for individuals with prehypertension than for those with normal blood pressure (95% CI 1.63–2.98) after adjusting for age, sex, and ethnicity. Prehypertension was not associated with incident diabetes after additional adjustment for BMI, impaired glucose tolerance, insulin resistance and secretion, and family history of diabetes (odds ratio 1.42 [95% CI 0.99–2.02]). CONCLUSIONS Subjects with prehypertension are at increased risk of diabetes. Much of this risk is explained by disorders related to the insulin resistance syndrome.
The developmental transcriptome of Drosophila melanogaster
Authors: Brenton Graveley
Journal: Genome biology (2010)

Drosophila melanogaster is one of the well-studied metazoan organisms; nonetheless its genome still contains unannotated genes, exons and RNA editing sites. Furthermore, our understanding of how the regulation of transcription, splicing and RNA editing directs development of this complex organism remains limited. We have used RNA-seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct stages throughout development. We have identified 87,352 new features, including thousands of genes, coding and non-coding transcripts, exons, splicing and editing events. We have inferred protein isoforms that previously eluded discovery with established experimental, prediction and conservation-based approaches. Together, these data substantially expand the number of known transcribed elements in the Drosophila genome and provide a high-resolution view of transcriptome dynamics throughout the development of a metazoan.
FULMINANT HEPATIC FAILURE: Pathophysiology, Treatment, and Survival
Authors: E. Atillasoy, M.D, P. D. Berk, M.D
Journal: Annual Review of Medicine (1995)

▪ Abstract Fulminant hepatic failure is characterized by severe metabolic derangements, neurologic complications and, ultimately, multiorgan failure. In the past three decades, improved intensive care has increased mean survival from 15% to 50% in certain patient groups by providing metabolic support and management of specific, frequent, and potentially fatal complications. However, outcome remains highly dependent on etiology. While intensive care is sufficient therapy in some patients (Group I), those with irreparable hepatic damage (Group III) can only survive if transplanted. In intermediate cases (Group II), the liver retains the potential to regenerate if the patient receives hepatic functional support. Major areas of current research in this field include development of hepatic support devices, strategies to accelerate and maximize hepatic regeneration, and criteria for accurate prognostic classification of patients.
Blood pleurodesis for the medical management of pneumothorax
Authors: S Rinaldi, T Felton, A Bentley
Journal: Thorax (2009)

Blood pleurodesis has been used to treat pneumothorax and persistent postoperative air leak following pneumonectomy. However, the indications for this procedure and the exact technique to be followed remain poorly defined. Having reviewed the current literature, a protocol is proposed for the technique and its complications and long-term outcomes are discussed.
Infection from intravenous "scalp-vein" needles in a susceptible population
Authors: S. Lowenbraum
Journal: JAMA (1970)

Intravenous indwelling scalp-vein needles were cultured in a population with neoplastic disease. Twenty-four of the 74 needles cultured were positive; microorganisms generally considered pathogenic grew from 7 of these needles. The latter organisms included<i>Staphylococcus aureus</i>,<i>Pseudomonas aeruginosa</i>,<i>Candida albicans</i>, α-hemolytic Streptococcus, and group D<i>Streptococcus</i>. Infected scalpvein needles were the bacteriologic source in one case of septicemia and one case of cellulitis. There was a trend toward increasing incidence of growth with increasing duration of needle placement.
In the beginning was the song: The complex multimodal timing of mother-infant musical interaction
Authors: Elena Longhi, Annette Karmiloff-Smith
Journal: Behavioral and Brain Sciences (2004)

In this commentary we raise three issues: (1) Is it motherese or song that sets the stage for very early mother-infant interaction? (2) Does the infant play a pivotal role in the complex temporal structure of social interaction? (3) Is the vocal channel primordial or do other modalities play an equally important role in social interaction?
T-Cell Suicide Gene Therapy for Organ Transplantation: Induction of Long-Lasting Tolerance to Allogeneic Heart without Generalized Immunosuppression
Authors: Eric Braunberger, José L. Cohen, Olivier Boyer, Béatrice Pegaz-Fiornet, Nathalie Raynal-Raschilas, Patrick Bruneval, Véronique Thomas-Vaslin, Bertrand Bellier, Alain Carpentier, Denis Glotz, David Klatzmann
Journal: Molecular Therapy (2000)

Standard immunosuppressive drugs used for allogeneic organ transplantation do not specifically target alloreactive T cells and must be given for the lifetime of the patient, resulting in significant morbidity and mortality. We aimed to induce experimental immune tolerance to vascularized heart allograft using a suicide gene allowing selective elimination of dividing T cells expressing Herpes simplex virus type 1 thymidine kinase upon ganciclovir administration. We show that without ganciclovir, transgenic mice selectively expressing thymidine kinase in T cells rejected a vascularized cardiac allograft in 7 days. In contrast, allograft was definitively accepted after a 7-day course of ganciclovir initiated at the time of allotransplantation. Interestingly, T cells from both rejecting and tolerant mice proliferated in response to donor or third-party allogeneic stimulation. This state of tolerance was challenged through a second vascularized cardiac allotransplantation. Third-party allografts were rejected while those syngeneic to the first allograft were accepted without any additional treatment. These results show that short-term pharmacogenetic immunosuppression can induce long-lasting, robust, and specific tolerance to solid vascularized allograft without generalized continuous immunosuppression. Standard immunosuppressive drugs used for allogeneic organ transplantation do not specifically target alloreactive T cells and must be given for the lifetime of the patient, resulting in significant morbidity and mortality. We aimed to induce experimental immune tolerance to vascularized heart allograft using a suicide gene allowing selective elimination of dividing T cells expressing Herpes simplex virus type 1 thymidine kinase upon ganciclovir administration. We show that without ganciclovir, transgenic mice selectively expressing thymidine kinase in T cells rejected a vascularized cardiac allograft in 7 days. In contrast, allograft was definitively accepted after a 7-day course of ganciclovir initiated at the time of allotransplantation. Interestingly, T cells from both rejecting and tolerant mice proliferated in response to donor or third-party allogeneic stimulation. This state of tolerance was challenged through a second vascularized cardiac allotransplantation. Third-party allografts were rejected while those syngeneic to the first allograft were accepted without any additional treatment. These results show that short-term pharmacogenetic immunosuppression can induce long-lasting, robust, and specific tolerance to solid vascularized allograft without generalized continuous immunosuppression.
Distinct Roles for SOS1 in the Convergent Evolution of Salt Tolerance in Eutrema salsugineum and Schrenkiella parvula
Authors: David E. Jarvis, Choong-Hwan Ryu, Mark A. Beilstein, Karen S. Schumaker
Journal: Molecular Biology and Evolution (2014)

Eutrema salsugineum and Schrenkiella parvula are salt-tolerant relatives of the salt-sensitive species Arabidopsis thaliana. An important component of salt tolerance is the regulation of Na+ ion homeostasis, which occurs in part through proteins encoded by the Cation/Proton Antiporter-1 (CPA1) gene family. We used a combination of evolutionary and functional analyses to examine the role of CPA1 genes in the salt tolerance of E. salsugineum and Sc. parvula, and found evidence that changes in CPA1-mediated Na+ extrusion may contribute to the salt tolerance of both species. Specifically, we found that a member of the CPA1 family, the Na+/H+ antiporter gene Salt Overly Sensitive 1 (SOS1), evolved under positive selection in E. salsugineum. In the absence of activation by the SOS2 kinase/SOS3 calcium-binding protein complex, SOS1 from E. salsugineum (EsSOS1) confers greater salt tolerance than SOS1 from Sc. parvula (SpSOS1) and Ar. thaliana (AtSOS1) when expressed in a salt-sensitive strain of Saccharomyces cerevisiae. A single amino acid change in the putative autoinhibitory domain is required but not sufficient for the enhanced salt tolerance conferred by EsSOS1. When activated by SOS2 and SOS3, both EsSOS1 and SpSOS1 confer greater salt tolerance than AtSOS1. Enhanced SOS1-mediated Na+ extrusion therefore appears to contribute to the salt tolerance of both E. salsugineum and Sc. parvula, although through apparently different mechanisms.
Bradykinin-induced bronchospasm in the rat in vivo: a role for nitric oxide modulation
Authors: T Homma, C.g Irvin
Journal: European Respiratory Journal (1999)

Bradykinin has an important role in asthma pathogenesis, but its site of action is unclear. It was previously reported by the authors that bradykinin causes a dose-dependent reduction in dynamic compliance but little change in total lung resistance. This suggested that bradykinin may have a preferential effect in the distant lung. The purpose of the current investigation was to better characterize the effects of bradykinin on pulmonary resistance in rodents and explore the role of nitric oxide release in modulating the effect of bradykinin. Airway constriction was induced in the rats by aerosol administration of bradykinin with or without treatments with the inhaled bradykinin-2 receptor antagonist, Hoe 140 or the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methylester or N(G)-monomethyl-L-arginine. Total lung resistance was partitioned into tissue and airway resistance by using the alveolar capsule method. Bradykinin induced a significant increase in both resistances. Hoe 140 abolished the response to bradykinin. The nitric oxide synthase inhibitors enhanced the bronchoconstricting response. In conclusion, the bradykinin response in the rats was not only localized to conducting airways but also involved a relatively selective tissue reaction. Bradykinin-induced bronchospasm in the rat is solely due to activation of bradykinin-2 receptor. Further, it was shown that nitric oxide significantly modulates the bronchospasm caused by bradykinin, suggesting that nitric oxide is an important modulator of airways responsiveness to bradykinin.
Cardiovascular profile of a new anti-arrhythmic agent, SC-40230
Authors: L. G FREDERICK, S. J McDONALD, S. M GARTHWAITE
Journal: Cardiovascular Research (1989)

The cardiac and general haemodynamic effects of SC-40230, a newly developed anti-arrhythmic agent with both class 1a and 1b properties, were assessed in two different types of experiments using anaesthetised dogs, and in experiments using isolated cat papillary muscles. At the canine anti-arrhythmic dose (9 mg.kg-1 intravenously), SC-40230 decreased the maximum rate of rise of the left ventricular pressure (LV dP/dtmax) by 20%. It decreased heart rate slightly, and lowered (greater than 10%) blood pressure only at doses greater than the canine anti-arrhythmic dose. In these experiments there were dose dependent increases in the P-R interval and the QRS duration. In isolated cat papillary muscles, SC-40230 had a weak negative inotropic effect (IC20 = 3.3 X 10(-5) mol.litre-1) which was less than that previously reported for disopyramide phosphate (IC20 = 1.8 X 10(-5) mol.litre-1) or mexiletine (IC20 = 2.1 X 10(-5) mol.litre-1). These findings suggest SC-40230 has a minimal cardiovascular and haemodynamic side effect potential in its anti-arrhythmic dose range. If these results are confirmed in clinical studies, SC-40230 may have an improved side effect profile versus other anti-arrhythmic drugs such as disopyramide.