gebhart/patrepeval huggingface dataset:
Future directions in magnetic resonance contrast media (1991)

In June 1988 Gd DTPA became the first MR contrast agent to be approved for clinical use in adult patients in the United States. Initial approval was given for its use in imaging of the head. One year later approval was extended to include spine studies. This was soon followed by approval for use in children aged 2 years and older. Research is continuing to expand the applications of Gd DTPA in MR imaging of the musculoskeletal system, abdomen, and in MR angiography. Research is ongoing in the development of new agents, attempting to reduce toxicity, permit increased doses, or target specific organs. Gd DOTA has been in clinical use in Europe for approximately 1 year. Two neutral (nonionic) agents, Gd HP-DO3A and Gd DTPA-BMA, have just completed phase III clinical trials. Mn DPDP and AMI-25 are two targeted compounds that have entered clinical trials. Formulations intended for opacification of the gastrointestinal tract, with both Gd DTPA and magnetic particles, have been evaluated in Europe and in the United States.
Endogenous regulation of angiogenesis in the rat aorta model. Role of vascular endothelial growth factor. (1997)

The purpose of this study was to investigate the role of vascular endothelial growth factor (VEGF) in the rat aorta model of angiogenesis. Freshly cut aortic rings generated microvascular outgrowths in serum-free collagen gel culture. Angiogenesis was reduced to 10% when the explants were embedded in collagen 10 to 14 days after excision from the animal. Immunochemical studies of conditioned medium demonstrated secretion of VEGF by the aortic cultures. Levels of VEGF decreased during the second week of culture when the explants became quiescent and microvessels stopped growing. Treatment of quiescent aortic rings with exogenous VEGF stimulated angiogenesis and restored microvascular growth to values observed in cultures of freshly cut explants. Reverse transcriptase polymerase chain reaction of vasoformative collagen gel cultures of rat aorta demonstrated the expression of the alternatively spliced isoforms VEGF165, VEGF189, and the high affinity VEGF receptor flk-1. Reverse transcriptase-polymerase chain reaction of rat aorta-derived cell strains confirmed the presence of VEGF165 and VEGF189 in endothelial cells, smooth muscle cells, and fibroblasts. The flk-1 receptor was expressed by endothelial cells but not by fibroblasts or smooth muscle cells, which is consistent with the endothelial target specificity of VEGF. The spontaneous angiogenic response of freshly cut aortic rings was inhibited by 70% with a neutralizing antibody against VEGF, whereas nonimmune IgG had no effect (P < 0.001). These findings provide evidence for a VEGF-mediated autocrine/paracrine regulation of angiogenesis in the rat aorta model.
Selective suppression of matrix metalloproteinase-9 in human glioblastoma cells by antisense gene transfer impairs glioblastoma cell invasion. (2000)

Increased expression of matrix metalloproteinases (MMPs) has been associated with human glioblastoma tumor progression. In this study, we sought to down-regulate MMP-9 expression by stably transfecting a high-grade glioblastoma cell line with a plasmid vector capable of expressing an antisense transcript complementary to a 528-bp segment at the 5' end of human MMP-9 cDNA. Stable transfectants were obtained through selection with G418. Of the clones transfected with vector, sense, and antisense constructs, Northern blotting, Western blotting, and gelatin zymography showed that MMP-9 expression was significantly reduced only in the antisense-transfected cells. A Matrigel invasion assay revealed marked reductions in invasiveness for the antisense clones relative to the parental, vector, and sense clones. Cocultures of tumor spheroids and fetal rat brain aggregates showed that the antisense-transfected stable clones showed no invasion of the rat brain aggregates; in contrast, 90% of the parental, vector, and sense clones invaded the rat brain aggregates. Intracerebral injection of antisense stable transfectants in nude mice produced no tumors or very small tumors, but intracerebral injection of parental or vector clones did produce tumors. These results suggest that MMP-9 expression is essential for the invasiveness of glioblastoma cells.
Effect of Omega‐3 Fatty Acid Supplementation on the Arachidonic Acid: Eicosapentaenoic Acid Ratio (2007)

Treatment with omega-3 fatty acids significantly reduced AA:EPA ratios in both healthy subjects and in patients with stable CAD. The treatment had no effect on hs-CRP levels in either group, and it reduced triglyceride levels in healthy subjects but not in patients with CAD.
Bone Marrow Cells Can Give Rise to Ameloblast-like Cells (2006)

Post-eruptive loss of ameloblasts requires identification of alternative sources for these cells to realize tooth-tissue-engineering strategies. Recent reports showed that bone-marrow-derived cells can give rise to different types of epithelial cells, suggesting their potential to serve as a source for ameloblasts. To investigate this potential, we mixed c-Kit + -enriched bone marrow cells with embryonic dental epithelial cells and cultured them in re-association with dental mesenchyme. Non-dividing, polarized, and secretory ameloblast-like cells were achieved without cell fusion. Before basement membrane reconstitution, some bone marrow cells migrated to the mesenchyme, where they exhibited morphological, molecular, and functional characteristics of odontoblasts. These results show, for the first time, that bone-marrow-derived cells can be reprogrammed to give rise to ameloblast-like cells, offering novel possibilities for tooth-tissue engineering and the study of the simultaneous differentiation of one bone marrow cell subpopulation into cells of two different embryonic lineages.
Inducible Degradation of IκBα In Vitro and In Vivo Requires the Acidic C-Terminal Domain of the Protein (1995)

After exposure of cells to tumor necrosis factor (TNF), I kappa B alpha is rapidly degraded by a proteolytic activity that is required for nuclear localization and activation of transcription factor NF-kappa B. To investigate this problem, we have developed a cell-free system to study the degradation of I kappa B alpha initiated in vivo. In this in vitro system, characteristics of endogenous I kappa B alpha degradation were comparable to those observed in vivo. Recombinant I kappa B alpha, when added to lysates from cells exposed to TNF, was specifically degraded by a cellular proteolytic activity; however, it was stable in extracts from unstimulated cells. Inhibition characteristics of the proteolytic activity responsible for I kappa B alpha degradation suggest the involvement of a serine protease. Analysis of mutated forms of I kappa B alpha in the in vitro system demonstrated that an I kappa B alpha species which was unable to interact with NF-kappa B was still efficiently degraded. In contrast, deletion of the C-terminal 61 amino acids from I kappa B alpha rendered the protein resistant to proteolytic degradation. Expression of I kappa B alpha mutated forms in COS-7 cells confirmed the importance of the C-terminal domain for the degradation of the protein in vivo following cell activation. Thus, it is likely that the acidic, negatively charged region represented by the C-terminal 61 amino acids of the protein contains residues critical for TNF-inducible degradation of I kappa B alpha.
Interferon-alpha (IFN-α) enhances cytotoxicity in healthy volunteers and chronic hepatitis C infection mainly by the perforin pathway (1999)

Cell-mediated cytotoxicity is exerted via perforin and Fas ligand (FasL). We have recently shown that IFN-alpha up-regulates FasL expression in T cells isolated from healthy volunteers and augments activation-induced T cell death. Since the Fas/FasL system is implicated in the pathogenesis of hepatic failure and both molecules have been shown to be up-regulated in hepatitis C virus (HCV) infection, we studied whether cytotoxicity via the FasL system is enhanced by IFN-alpha and therefore could contribute to hepatic injury. We investigated FasL and perforin expression in peripheral blood mononuclear cells (PBMC) derived from HCV+ donors by Northern analysis and soluble FasL synthesis by ELISA. Natural killer (NK) cell and cytotoxic T lymphocyte (CTL) cytotoxicity was studied by 51Cr-release assays. IFN-alpha up-regulates FasL mRNA and protein synthesis in mitogen-activated PBMC of HCV+ individuals, as previously found in healthy subjects. Stimulation with IFN-alpha increases perforin mRNA levels in PBMC. In NK cytotoxicity assays, the enhancement of cytotoxicity by IFN-alpha is mainly due to the perforin pathway, while the FasL pathway plays only a minor role. In CTL cytotoxicity experiments neither the FasL nor the perforin pathway is further enhanced by IFN-alpha. Our data suggest that up-regulation of perforin by IFN-alpha results in elevated cytotoxicity, suggesting that IFN-alpha might support elimination of virally infected cells via this pathway. In contrast, the major effect of IFN-alpha on the Fas/FasL system might be the enhanced elimination of activated T cells as a means of finally limiting a T cell response.
Telomere Shortening in Familial and Sporadic Pulmonary Fibrosis (2008)

A significant fraction of individuals with pulmonary fibrosis have short telomere lengths that cannot be explained by coding mutations in telomerase. Telomere shortening of circulating leukocytes may be a marker for an increased predisposition toward the development of this age-associated disease.
Hydroxylation of HIF-1: Oxygen Sensing at the Molecular Level (2004)

The ability to sense and respond to changes in oxygenation represents a fundamental property of all metazoan cells. The discovery of the transcription factor HIF-1 has led to the identification of protein hydroxylation as a mechanism by which changes in PO2 are transduced to effect changes in gene expression.
Evidence for a gene on 17p13.3, distal to TP53, as a target for allele loss in breast tumors without p53 mutations. (1994)

In breast cancer, loss of heterozygosity (LOH) on 17p is a frequent event and a likely target is the p53 gene on 17p13.1. However, several LOH mapping studies have indicated that, in some breast tumors, LOH affects only the most distal 17p markers, suggestive of a second tumor suppressor locus in 17p13.3. In order to distinguish which gene has most probably served as the target for LOH on 17p, we have screened 141 breast tumors for somatic mutations in the p53 gene in conjunction with detailed LOH mapping on the short arm of chromosome 17. A total of 32 mutations were detected in 31 tumors, 15 of which have never been reported in breast cancer before. The majority are point mutations leading to an amino acid change in the protein. In addition, we have stained a subset of 87 tumors for the p53 protein by immunohistochemistry. In 21 of these tumors (24%), nuclear staining was detected in over 25% of the tumor cells with the anti-p53 antibody DO7. A positive correlation was found between p53-positive staining and p53 mutation (P < 0.001). A strong association was observed between p53 mutation and LOH at the TP53 locus but not between p53 expression and LOH on 17p. In breast tumors without a detectable p53 mutation but with LOH on 17p, the 17p13.3 region is always involved and, in some cases, even exclusively involved. These results suggest that a second tumor suppressor gene, located distal to TP53, is targeted by LOH on 17p in some breast tumors and that a substantial number of breast tumors stabilize p53 through mechanisms other than mutation.
Effect of atrial septostomy on the survival of patients with severe pulmonary arterial hypertension (2011)

Atrial septostomy (AS) is a palliative treatment for right ventricular failure from severe pulmonary arterial hypertension (PAH). We sought to investigate the effect of AS, alone or combined with PAH-specific pharmacotherapy, on the survival of patients with PAH. We performed a retrospective analysis of the functional and haemodynamic changes in patients with PAH following AS, and long-term survival characteristics for the whole group and separately for the subgroup who received post-procedural pharmacotherapy. 50 procedures performed in 34 patients (mean ± SD age 35 ± 10 yrs) resulted in haemodynamic and symptomatic improvement in most of the patients. Only one (2%) procedure-related death occurred. Due to spontaneous closure of the defect, AS was repeated in 10 patients. In 21 patients, AS was the only form of treatment, while 11 received additional pharmacotherapy after AS. During follow-up (58.5 ± 38 months), 21 patients died; median survival of the group was 60 months (95% CI 43-77 months). Median survival for patients on pharmacotherapy additional to AS was 83 months (95% CI 57-109 months), which was better than that for patients with AS alone (53 months, 95% CI 39-67 months) (log-rank 6.52; p = 0.010). In selected patients with PAH, AS is a safe and effective intervention that exerts a beneficial impact on long-term survival. Survival appears to be improved when AS is combined with PAH-specific pharmacotherapy.
Surgical Wound Case Studies With the Versatile 1 Wound Vacuum System for Negative Pressure Wound Therapy (2006)

Negative pressure wound therapy consists of a wound dressing, a drainage tube inserted into the dressing, an occlusive transparent film, and a connection to a vacuum source that supplies the negative pressure. A new product called the Versatile 1 Wound Vacuum System (BlueSky Medical, La Costa, Calif) is available for negative pressure wound therapy. This article describes the application, management, and effectiveness of the Versatile 1 in 3 cases where the patients have all undergone surgical debridement.
High Mechanical Performance Composite Conductor: Multi‐Walled Carbon Nanotube Sheet/Bismaleimide Nanocomposites (2009)

Abstract Multi‐walled carbon nanotube (MWNT)‐sheet‐reinforced bismaleimide (BMI) resin nanocomposites with high concentrations (∼60 wt%) of aligned MWNTs are successfully fabricated. Applying simple mechanical stretching and prepregging (pre‐resin impregnation) processes on initially randomly dispersed, commercially available sheets of millimeter‐long MWNTs leads to substantial alignment enhancement, good dispersion, and high packing density of nanotubes in the resultant nanocomposites. The tensile strength and Young's modulus of the nanocomposites reaches 2 088 MPa and 169 GPa, respectively, which are very high experimental results and comparable to the state‐of‐the‐art unidirectional IM7 carbon‐fiber‐reinforced composites for high‐performance structural applications. The nanocomposites demonstrate unprecedentedly high electrical conductivity of 5 500 S cm −1 along the alignment direction. Such unique integration of high mechanical properties and electrical conductance opens the door for developing polymeric composite conductors and eventually structural composites with multifunctionalities. New fracture morphology and failure modes due to self‐assembly and spreading of MWNT bundles are also observed.
Helicobacter felis gastritis in gnotobiotic rats: an animal model of Helicobacter pylori gastritis (1991)

The gastric spirillum Helicobacter felis, originally isolated from the cat stomach, colonizes the stomachs of germfree rats. Studies were designed to examine the pathological and serological responses of germfree rats inoculated orally with H. felis. At 2 weeks postinoculation, the gastric mucosa of germfree rats had lymphocytes and eosinophils scattered in small foci throughout the subglandular region of the antrum. Small numbers of lymphocytes were present in the subglandular portion of the antral mucosa that focally extended through the lamina propria towards the luminal surface. Eight weeks postinoculation, the inflammation was confined to the antrum. It was characterized by increased numbers of lymphocytes and eosinophils in the subglandular areas, with focal aggregates of lymphocytes in the submucosa. Some lymphoid aggregates extended from the submucosa through the muscularis mucosa and lamina propria to the luminal surface. H. felis was demonstrated with the Warthin-Starry stain, bacterial culture, and urease assay, particularly in the antrum. H. felis also produced a significant immunoglobulin G antibody titer at 2, 4, and 8 weeks postinoculation as well as a transitory immunoglobulin M response at 2 to 4 weeks postinoculation. Contact control rats were not infected, inferring that fecal-oral spread of H. felis did not occur.
Demonstration of the stem cell nature of clonogenic tumor cells from lung cancer patients. (1982)

The tumor cell colony-forming efficiency in soft agarose was evaluated in 190 specimens obtained from patients with either small cell carcinoma of the lung (SCCL) or adenocarcinoma of the lung (ACL). Tumor cell colony formation was observed in 45 out of 53 (84%) specimens containing cytopathologically identifiable SCCL tumor cells obtained from a variety of metastatic sites. Tumor cell colony formation was also observed in 6 out of 10 specimens containing ACL tumor cells. The colony-forming efficiency for these lung cancer specimens ranged from 0.003 to 0.72% per nucleated cell plated and from 0.05 to 1.5% per tumor cell plated. There were no differences in plating efficiency for SCCL and ACL. The tumor cell origin of the cells in the agarose colonies was confirmed by cytologic examination, flow cytometric DNA content analysis, and electron microscopy examination. The 'stem cell' nature was demonstrated by the ability of colonies to form typical SCCL or ACL tumors when inoculated into athymic nude mice. In addition, continuous tumor cell lines were established from several specimens forming tumors in nude mice. These data confirm the tumor cell origin and 'stem cell' nature of lung cancer cell colonies growing in soft agarose. Whether the low colony-forming efficiency represents a property inherent in the tumor cells, or a defect in the culture system, remains to be determined.
Sequence Comparison Between the Fusion Protein of Human and Bovine Espiratory Syncytial Viruses (1990)

The nucleotide sequence was determined for the fusion (F) protein-coding mRNA of the bovine respiratory syncytial virus (strain RB 94) and the amino acid sequence of the F protein was deduced for comparison with the sequence of human respiratory syncytial virus subtypes A and B (RSS-2 and 18537 strains). The human and bovine RS virus F proteins (excluding the cleaved signal peptide) share 83 to 84% homology. The greatest divergence occurred within the F2 subunit in the region preceding the cleavage activation site.
Superoxide anion participation in human monocyte-mediated oxidation of low-density lipoprotein and conversion of low-density lipoprotein to a cytotoxin. (1989)

Human monocytes, upon activation with opsonized zymosan, altered low-density lipoprotein (LDL) during a 24-h co-incubation, resulting in its oxidation and acquisition of cytotoxic activity against target fibroblast cell lines. Both the oxidation of LDL and its conversion to a cytotoxin were enhanced with time of incubation, with the most substantial changes occurring after 6 h of culture of LDL with activated monocytes. Unactivated monocytes did not mediate either alteration. Superoxide anion (O2-) participated in both the oxidation of LDL and its conversion to a cytotoxin since addition of superoxide dismutase (SOD) at the beginning of the co-incubation inhibited, in a concentration dependent fashion, both the monocyte-mediated oxidation and the monocyte-mediated conversion of LDL to a cytotoxin. As expected, the rate of superoxide anion release was greatest during the respiratory burst, very early in the 24-h incubation (0 to 2 h); however, exposure of LDL to monocytes during the respiratory burst was not required for LDL oxidation. The lower levels of O2- released by the cells hours after the respiratory burst had subsided were sufficient to lead to the initiation of LDL oxidation. Three results indicated that the oxidative modification of LDL into a cytotoxin required O2(-)-independent free radical propagation after O2(-)-dependent initiation. First, oxidation of LDL exposed to the activated, superoxide anion-releasing monocytes for 6 h could be almost completely blocked by the addition at 6 h of the general free radical scavenger butylated hydroxytoluene, but not by SOD. Second, LDL oxidation proceeded even after removal of LDL from the superoxide anion-producing, activated cells after various durations of exposure. Third, the development of substantial levels of lipid peroxidation products and the development of greater cytotoxicity occurred after 6 h of exposure of LDL to activated cells, long after peak O2- release had subsided. These results lead us to conclude that monocyte-mediated oxidation of LDL, leading to its transformation into a cytotoxin, requires release of O2- occurring as a result of activation but not necessarily during the respiratory burst, and also requires O2(-)-independent free radical propagation. The modification of LDL into a potent toxin by activated monocytes may explain the tissue damage in atherosclerotic lesions and other pathologic sites in which inflammatory cells congregate.
MEKK1 Binds Directly to the c-Jun N-terminal Kinases/Stress-activated Protein Kinases (1997)

Mitogen-activated protein (MAP) kinases mediate responses to a wide array of cellular stimuli. These cascades consist of a MAP kinase or extracellular signal-regulated kinase (ERK), activated by a MAP/ERK kinase (MEK), in turn activated by a MEK kinase (MEKK). MEKK1 has been shown to be a strong activator of the c-Jun N-terminal kinase/stress-actived protein kinase (JNK/SAPK) pathway. We report here that JNK/SAPK binds directly to the N-terminal, noncatalytic domain of MEKK1 in vitro and in transfected cells. Immobilized MEKK1-derived peptides extract JNK/SAPK selectively from cell lysates. MEKK1 coimmunoprecipitates with multiple JNK/SAPK isoforms in transfected cells. Expression of the N terminus of MEKK1 lacking the kinase domain increases activation of endogenous JNK/SAPK by MEKK1. The data are consistent with a model in which MEKK1-JNK/SAPK binding facilitates the receipt of signals from upstream inputs and localizes JNK/SAPK to intracellular targets of the pathway.
Production of Bioactive Diterpenoids in the Euphorbiaceae Depends on Evolutionarily Conserved Gene Clusters (2014)

The Euphorbiaceae produce a diverse range of diterpenoids, many of which have pharmacological activities. These diterpenoids include ingenol mebutate, which is licensed for the treatment of a precancerous skin condition (actinic keratosis), and phorbol derivatives such as resiniferatoxin and prostratin, which are undergoing investigation for the treatment of severe pain and HIV, respectively. Despite the interest in these diterpenoids, their biosynthesis is poorly understood at present, with the only characterized step being the conversion of geranylgeranyl pyrophosphate into casbene. Here, we report a physical cluster of diterpenoid biosynthetic genes from castor (Ricinus communis), including casbene synthases and cytochrome P450s from the CYP726A subfamily. CYP726A14, CYP726A17, and CYP726A18 were able to catalyze 5-oxidation of casbene, a conserved oxidation step in the biosynthesis of this family of medicinally important diterpenoids. CYP726A16 catalyzed 7,8-epoxidation of 5-keto-casbene and CYP726A15 catalyzed 5-oxidation of neocembrene. Evidence of similar gene clustering was also found in two other Euphorbiaceae, including Euphorbia peplus, the source organism of ingenol mebutate. These results demonstrate conservation of gene clusters at the higher taxonomic level of the plant family and that this phenomenon could prove useful in further elucidating diterpenoid biosynthetic pathways.