gebhart/patrepeval huggingface dataset:
Antigen-presenting B cells and helper T cells cooperatively mediate intravirionic antigenic competition between influenza A virus surface glycoproteins. (1987)

Parenteral vaccination of BALB/c mice primed by infection with H3N2 variants of influenza A virus results in a reduced production of N2 antibody in response to homologous (H3N2) vaccine compared with the response to an H7N2 vaccine equal in N2 immunologenicity. We now have studied the interaction in vitro of purified splenic B and T lymphocytes from variably immunized mice to ascertain the cellular basis of the hemagglutinin (HA)-influenced antibody response to neuraminidase (NA). Assay of the proliferative response of T cells in B/T-cell mixtures stimulated by H3N1 (HA-specific) and H6N2 (NA-specific) reassortant (recombinant) viruses in vitro has enabled us to differentiate cellular responses to HA and NA antigens. Using a factorial design in analysis of B/T-cell mixtures, we have shown that: (i) intravirionic HA is dominant over NA in both B- and T-cell priming; (ii) an increase in H3-specific B cells occurs in mice administered boosters of H3N2 vaccine, and an increase in N2-specific B cells occurs in those given a booster of H7N2 vaccine; and (iii) memory B cells function as antigen-presenting cells and interact with memory helper T cells in the mediation of intravirionic HA-NA antigenic competition in favor of HA. The damping of response to the NA antigen in favor of HA with reinfection prohibits balanced immunologic response to the two antigens. The present studies define further the complex immunology of influenza virus infection.
Rising incidence of insulin dependent diabetes in children aged under 5 years in the Oxford region: time trend analysis (1997)

Incidence of insulin dependent diabetes in children aged under 5 years has risen markedly in the Oxford region over the past decade. The cause of the increase is unknown, but environmental influences encountered before birth or in early postnatal life are likely to be responsible.
Specific Inhibition of Expression of a Human Collagen Gene (COL1A1) with Modified Antisense Oligonucleotides. The Most Effective Target Sites are Clustered in Double-Stranded Regions of the Predicted Secondary Structure for the mRNA (1994)

A series of antisense oligonucleotides (ASOs) were synthesized and tested to define the best target sites within an RNA transcript of collagen for effective inhibition of expression. The test system consisted of mouse NIH 3T3 fibroblasts that were stably transfected with a human minigene for procollagen I so that the cells simultaneously synthesized full-length mouse pro alpha 1 (I) chains and internally deleted human pro alpha 1 (I) chains. The sequences of the transcripts from both genes were compared, and a series of 28 ASOs were designed to target sites in which there were at least two base differences within a 20-nucleotide sequence between the human and mouse transcripts. Six of the ASOs specifically decreased the levels of pro alpha 1 (I) chain synthesized from the human gene without a decrease in the levels of pro alpha 1 (I) chains from the mouse endogenous gene. The most effective ASOs reduced the intracellular levels of human pro alpha 1 (I) chains relative to the mouse pro alpha 1 (I) chains to 37-67% of the control values. Combined addition of two effective ASOs or a second administration of the same effective ASO did not produce any additive effect. The results did not support previous suggestions that the best target sites for ASOs were sequences around initiation codons for translation, at intron-exon boundaries, or in single-stranded loops in hairpin structures. Also, the results did not support previous suggestions that the most effective ASOs are those with the highest affinities for their target sequences. Instead, the most consistent pattern in the data was that the most effective ASOs were those targeted to sequences that were predicted to form clustered double-stranded structures in RNA transcripts.
Carotid Artery Atherosclerosis: In Vivo Morphologic Characterization with Gadolinium-enhanced Double-oblique MR Imaging—Initial Results (2002)

In nine subjects with carotid atherosclerosis, double-oblique, contrast material-enhanced, double inversion-recovery, fast spin-echo magnetic resonance (MR) images were acquired through atheroma in the proximal internal carotid artery. Fibrocellular tissue within atheroma selectively enhanced 29% after administration of gadolinium-based contrast agent. Contrast enhancement helped discriminate fibrous cap from lipid core with a contrast-to-noise ratio as good as or better than that with T2-weighted MR images but with approximately twice the signal-to-noise ratio (postcontrast images, 36.6 +/- 3.6; T2-weighted images, 17.5 +/- 2.1; P <.001).
N-13 ammonia as an indicator of myocardial blood flow. (1981)

We have characterized N-13 ammonia as a myocardial blood flow imaging agent suitable for positron-emission computed tomography. However, the mechanisms of uptake and retention of this agent in myocardium are not known, and effects of altered metabolism were not considered. Therefore, we studied the uptake and retention of N-13 ammonia in myocardium under various hemodynamic and metabolic conditions in open-chest dogs. N-13 ammonia was extracted nearly 100% during its initial capillary transit, followed by metabolic trapping that competed with flow-dependent back diffusion. At control flows, the first capillary tran- sit extraction fraction (E) of N-13 ammonia averaged 0.82 0.06. It fell with higher flows by E = 1 -0.607 exp -125/F. Myocardial N-13 tissue clearance half-times were similarly inversely related to blood flow, and ranged from 110-642 minutes. Cardiac work and changes in the myocardial inotropic state induced by isopro- terenol and propranolol did not affect E or the tissue clearance half-times. Low plasma pH reduced E by an average of 20%, while elevated plasma pH had no effect. Decreases in flow below control also were associated with a fall in E. Inhibition of glutamine synthetase with L-methionine sulfoximine impaired metabolic trapping of N-13 ammonia and implicates the glutamic acid-glutamine reaction as the primary mechanism for ammonia fixation. The product of E times flow predicts the myocardial N-13 tissue concentrations, which increased by 70% when flow was doubled. Thus, blood flow and metabolic trapping are the primary determinants of myocar- dial uptake and retention of N-13 ammonia. The relative constancy of metabolic trapping over a wide range of hemodynamic and metabolic conditions demonstrates the value of N-13 ammonia as a myocardial blood flow imaging agent.
The Human retroviruses (1991)

(Section Headings): Molecular Biology. Biology. Epidemiology. Animal Models. Therapy. Index.
Platelet reactivity is a stable and global phenomenon in aspirin-treated cardiovascular patients (2011)

In healthy subjects, platelet hyperreactivity is a global phenomenon--as opposed to agonist-specific--and epinephrine-induced platelet aggregation (EPA) is a reliable marker of this phenotype. Few data are available on platelet reactivity and the relationship between EPA and aggregation induced by other agonists in cardiovascular patients. It was the objective of this study to characterise platelet reactivity in stable cardiovascular patients treated with aspirin and to derive a composite index integrating several aggregation pathways, suitable for selecting patients with extreme phenotypes for further proteomics analysis. Platelet reactivity to agonists was assessed in 110 patients twice, two weeks apart. Factorial analysis was used to determine whether the results obtained with the different agonists could be summarised in a single composite index. EPA correlated with the aggregation values obtained with each of the other agonists, with correlation coefficients of 0.44 to 0.55 (p < 0.001). We constructed a composite "platelet reactivity" index that included 60% of the information provided by each agonist. The results obtained at the first patient visit were consistent with those obtained at the second visit (r = 0.78, p<0.01). No clinical or biological parameters correlated with the composite index. The extreme phenotypes of six selected subjects were confirmed 12 months after the second visit. In conclusion, platelet reactivity in aspirin-treated cardiovascular patients is a global phenomenon that can be summarised by a composite index based on the aggregation responses to various agonists and integrating several activation pathways. This index is not dependent on clinical or biological variables, suggesting that genetic factors regulate platelet reactivity in these patients.
A machine program for theorem-proving (1962)

The programming of a proof procedure is discussed in connection with trial runs and possible improvements.
The Long Form of FLIP Is an Activator of Caspase-8 at the Fas Death-inducing Signaling Complex (2002)

Death receptors, such as Fas and tumor necrosis factor-related apoptosis-inducing ligand receptors, recruit Fas-associated death domain and pro-caspase-8 homodimers, which are then autoproteolytically activated. Active caspase-8 is released into the cytoplasm, where it cleaves various proteins including pro-caspase-3, resulting in apoptosis. The cellular Fas-associated death domain-like interleukin-1-beta-converting enzyme-inhibitory protein long form (FLIP(L)), a structural homologue of caspase-8 lacking caspase activity because of several mutations in the active site, is a potent inhibitor of death receptor-induced apoptosis. FLIP(L) is proposed to block caspase-8 activity by forming a proteolytically inactive heterodimer with caspase-8. In contrast, we propose that FLIP(L)-bound caspase-8 is an active protease. Upon heterocomplex formation, a limited caspase-8 autoprocessing occurs resulting in the generation of the p43/41 and the p12 subunits. This partially processed form but also the non-cleaved FLIP(L)-caspase-8 heterocomplex are proteolytically active because they both bind synthetic substrates efficiently. Moreover, FLIP(L) expression favors receptor-interacting kinase (RIP) processing within the Fas-signaling complex. We propose that FLIP(L) inhibits caspase-8 release-dependent pro-apoptotic signals, whereas the single, membrane-restricted active site of the FLIP(L)-caspase-8 heterocomplex is proteolytically active and acts on local substrates such as RIP.
The role of labeled Annexin A5 in imaging of programmed cell death. From animal to clinical imaging. (2003)

Programmed cell death plays a critical role in embryology, homeostasis and disease. However, until recently no non-invasive imaging modality has been able to visualize this process directly. Annexin A5 binds to cells undergoing programmed cell death. When labeling this protein, Annexin A5 becomes a tool for the detection of programmed cell death in vitro and in vivo. Labeled Annexin A5 has enabled our group and others to detect programmed cell death non-invasively in animals and patients. This review will highlight the development of this imaging modality in cellular and animal models. Furthermore, we will discuss Annexin A5 imaging in human disease. We will focus on the clinical applications and their relevance, limitations and future perspectives of non-invasive imaging of programmed cell death using labeled Annexin A5.
The Role of Muscle Loss in the Age-Related Decline of Grip Strength: Cross-Sectional and Longitudinal Perspectives (1990)

The decline of strength with age has often been attributed to declining muscle mass in older subjects. To investigate factors which might influence changes in strength across the life span, grip strength and muscle mass (as estimated by creatinine excretion and forearm circumference) were measured in 847 healthy volunteers, aged 20-100 years, from the Baltimore Longitudinal Study of Aging. Cross-sectional and longitudinal results concur that grip strength increases into the thirties and declines at an accelerating rate after age 40. However, the grip strength of 48% of subjects less than 40 years old, 29% of individuals 40-59 years old, and 15% of subjects older than 60 did not decline during the average 9-year follow-up. Grip strength is strongly correlated with muscle mass (r = .60, p less than .0001). However, using multiple regression analysis, grip strength is more strongly correlated with age (partial r2 = .38) than muscle mass (partial r2 = .16). Additionally, a residuals analysis demonstrates that younger subjects are stronger and older subjects are weaker than one would predict based on their muscular size. Thus, while strength losses are partially explained by declining muscle mass, there remain other yet undetermined factors beyond declining muscle mass to explain some of the loss of strength seen with aging.
A Review of Collagen and Collagen-based Wound Dressings. (2008)

﻿Collagen is a key component of a healing wound. In this review, a general description of the wound healing process is provided focusing on collagen's unique role. The mode of action (MoA) of collagen-based dressings is also addressed. Due to a number of potential stimuli (local tissue ischemia, bioburden, necrotic tissue, repeated trauma, etc.), wounds can stall in the inflammatory phase contributing to the chronicity of the wound. One key component of chronic wounds is an elevated level of matrix metalloproteinases (MMPs). At elevated levels, MMPs not only degrade nonviable collagen but also viable collagen. In addition, fibroblasts in a chronic wound may not secrete tissue inhibitors of MMPs (TIMPs) at an adequate level to control the activity of MMPs. These events prevent the formation of the scaffold needed for cell migration and ultimately prevent the formation of the extracellular matrix (ECM) and granulation tissue. Collagen based wound dressings are uniquely suited to address the issue of elevated levels of MMPs by acting as a 'sacrificial substrate' in the wound. It has also been demonstrated that collagen breakdown products are chemotactic for a variety of cell types required for the formation of granulation tissue. In addition, collagen based dressings have the ability to absorb wound exudates and maintain a moist wound environment.
Reduction of the survival time of pig xenotransplants by porcine cytomegalovirus (2018)

Although it is still unknown whether PCMV infects primate cells including human cells, indirect mechanism of the virus infection may cause reduction of the xenotransplant survival in future clinical trials and therefore PCMV has to be eliminated from donor pigs.
Treatment of mantle cell lymphoma: targeting the microenvironment (2005)

Mantle cell lymphoma is a distinct entity among the non-Hodgkin's lymphomas characterized by a specific chromosomal translocation, the t(11;14)(q13;q32), overexpression of cyclin-D1 and frequent disease manifestations at extranodal sites. Mantle cell lymphoma remains difficult to treat and belongs to the lymphomas with the poorest long-term outcome. Recent advances in our understanding of lymphoma biology suggest that both alterations of the lymphoma cells themselves and interactions with the microenvironment are important for the growth and survival of the malignant B-cell clone. This novel approach to therapy is being exploited by evaluating drugs such as bortezomib and thalidomide that target interactions between tumor cells and cells of the microenvironment. Thus, with the use of novel therapeutic interventions, it is hoped that clinicians will be able to improve the outcome of patients with mantle cell lymphoma.
Aerosols in Medicine : Principles, Diagnosis and Therapy (1993)

Part 1 Upper Airway - Structure, Function and Therapy (N. Mygind): Introduction. Anatomy of the nose. Applied physiology of the nose. Pathology of rhinitis. Aerosol therapy in the nose. Pharynx and larynx. References. Part 2 Lower Airway - Structure and Function (J.B. Forrest): Introduction. General organization of lung structure. Acknowledgements. References. Part 3 Aerosol Characterization and Generation (D.L. Swift): Characteristics of aerosols. Aerosol generation. References. Part 4 Airflow Dynamics in the Human Airways (H.K. Chang, A.S. Menon): Introduction. Airway models. Flow in the large airways (trachea, main and lobar bronchi). Flow in the upper airways (nose, nasopharynx, mouth, oropharynx, pharynx and anterior larynx). Relevance of fluid dynamics to particle deposition. References. Part 5 Mechanisms of Particle Deposition and Clearance (J.D. Brain, J.D. Blanchard): Introduction. Particle transport and deposition mechanisms. Characterizing and delivering therapeutic aerosol. Factors influencing particle deposition. Selecting deposition patterns. Clearance and retention of particles. Cough. Measuring particle retention. Conclusions. References. Part 6 Models of Aerosol Behaviour in Airways and Alveoli (P.E. Morrow, C.P. Yu): Introduction. Particle deposition. Particle removal from the respiratory system. Acknowledgement. References. Part 7 Aerosols in Diagnosis - Ventilation, Airway Penetrance, Epithelial Permeability, Mucociliary Transport and Airway Responsiveness (M.B. Dolovich, D.W. Cockcroft, G. Coates): Introduction. Aerosols and the assessment of ventilation. Aerosol penetrance in the assessment of airway obstruction. Aerosol and airway pharmacological responses. Aerosols in the assessment of pulmonary epithelial permeability. Aerosols in the assessment of mucociliary transport. Use of aerosols in assessment of airway responsiveness. Acknowledgement. References. Part 8 Epithelial Permeability (R.M. Effros): Introduction. Correlation of structure and permeability. Indicator properties which affect transport. Reflection coefficients of the pulmonary epithelium. Radioaerosol studies. Active transport across the pulmonary epithelium. Clinical applications of radioaerosol clearance. References. Part 9 Airway Mucus Clearance and Mucociliary Transport (P. Camner, B. Mossberg): Introduction. Basic data. Importance of mucociliary clearance. Lung diseases. Interventions. Environmental factors. References. Part 10 Bronchial Asthma, Chronic Bronchitis and Pulmonary Parenchymal Diseases (0. Selroos): Introduction. Drugs for inhalation. Delivery systems. Clinical indications. References. Part 11 Pulmonary Infections (C. Breese Hall, J.T. McBride): Introduction. Aerosolised antibacterial agents. Aerosolised chemoprophylactic therapy for Pneumocystis carinii. Aerosolised antiviral agents. Environmental agents. Summary. References. (Part contents).
Induction of tumor-infiltrating lymphocytes in human malignant melanoma metastases by immunization to melanoma antigen vaccine. (1989)

We report a statistically significant increase in tumor-infiltrating lymphocytes in subcutaneous melanoma metastases removed from patients immunized with a melanoma vaccine. Dense cellular infiltrates were seen in 10 of 11 nodules from vaccine-immunized patients, compared with 9 of 22 nodules from non-immunized patients (p = 0.02). Furthermore, these dense lymphocytic collections more frequently infiltrated the body of tumor nodules from immunized patients, whereas in non-immunized patients, lymphocytes were more often present only in the dermal tissue at the periphery of the nodule. Thus, allogeneic melanoma vaccines may augment immune responses to a patient's own tumor.
Improved Immunogenicity of a Vaccination Regimen Combining a DNA Vaccine Encoding Brucella melitensis Outer Membrane Protein 31 (Omp31) and Recombinant Omp31 Boosting (2007)

In the present study, we report an attempt to improve the immunogenicity of the Omp31 antigen by a DNA prime-protein boost immunization regimen. We immunized BALB/c mice with an Omp31 DNA vaccine (pCIOmp31) followed by boosting with recombinant Omp31 (rOmp31) in incomplete Freund's adjuvant and characterized the resulting immune responses and the protective efficacy against Brucella ovis and B. melitensis infection. Immunoglobulin G1 (IgG1) and IgG2a titers were higher in sera from pCIOmp31/rOmp31-immunized mice than in sera from mice immunized with pCIOmp31 or rOmp31 alone. Splenocytes from pCIOmp31/rOmp31-immunized mice produced significantly higher levels of gamma interferon than did those from mice given rOmp31 alone. In contrast, interleukin 2 (IL-2) production levels were comparable between the two groups of immunized mice. Cells from all immunized mice produced undetectable levels of IL-4. Notably, rOmp31 stimulated IL-10 production in the pCIOmp31/rOmp31-immunized group but not in the pCIOmp31- or rOmp31-immunized group. Although the prime-boost regimen induced specific cytotoxic responses, these responses could not reach the levels achieved by the pCIOmp31 immunization. In conclusion, pCIOmp31 priming followed by rOmp31 boosting led to moderately improved protection against a challenge with B. ovis or B. melitensis.
Absorption, distribution, and excretion of 5-azacytidine (NSC-102816) in man. (1972)

Patients with advanced cancer were given 5-azacytidine labeled at position 4 with radioactive carbon (14C) by either the intravenous (iv) or subcutaneous (sc) route. Absorption of the drug from the sc injection site was rapid and peak plasma levels were attained within one-half hour. Within 2 hours, the plasma level of radioactivity was approximately equal to that noted in the patients treated iv. The plasma half-life after iv injection was 3.5 hours; after sc administration, the plasma half-life was 4.2 hours. Patients receiving the drug sc excreted less drug in the urine than did those receiving the drug iv. No radioactivity was detected in the expired carbon dioxide when the drug was given by either route. Drug uptake into tumor tissue was always greater than uptake into surrounding normal tissue. The highest concentrations of radioactivity in the tissues were achieved when the drug had been given iv. Traces of radioactivity were still detectable in the tissues for as long as 6 days after administration of the drug. The incorporation of radioactivity into tumor RNA but not into DNA was demonstrated. The maximum level of radioactivity detected in the spinal fluid was equivalent to 0.2 microg of 5-azacytidine per milliliter of fluid.
Ypr140wp, ‘the yeast tafazzin’, displays a mitochondrial lysophosphatidylcholine (lyso-PC) acyltransferase activity related to triacylglycerol and mitochondrial lipid synthesis (2005)

When the yeast protein Ypr140w was expressed in Escherichia coli, a lyso-PC [lysophosphatidylcholine (1-acylglycerophosphorylcholine)] acyltransferase activity was found associated with the membranes of the bacteria. To our knowledge, this is the first identification of a protein capable of catalysing the acylation of lyso-PC molecules to form PC. Fluorescence microscopy analysis of living yeasts revealed that the fusion protein Ypr140w-green fluorescent protein is targeted to the mitochondria. Moreover, in contrast with wild-type cells, in the absence of acyl-CoA, the yeast mutant deleted for the YPR140w gene has no lyso-PC acyltransferase activity associated with the mitochondrial fraction. When yeast cells were grown in the presence of lactate, the mutant synthesized 2-fold more triacylglycerols when compared with the wild-type. Moreover, its mitochondrial membranes contained a lesser amount of PC and cardiolipin, and the fatty acid composition of these latter was greatly changed. These modifications were accompanied by a 2-fold increase in the respiration rates (states 3 and 4) of the mitochondria. The relationship between the deletion of the YPR140w gene and the lipid composition of the ypr140wDelta cells is discussed.